Conditions: Philadelphia Chromosome Positive (PH+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Keywords: Adult Chronic myelogenous leukemia (CML) Chronic myeloid leukemia (CML) Chronic myelocytic leukemia (CML) Acute Lymphoblastic Leukemia (ALL) Philadelphia chromosome positive Acute Lymphoid Leukemia Suboptimal molecular response
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 620
Healthy volunteers: no

Brief summary:
This study aimed to assess the optimal duration of nilotinib 300 mg twice daily (BID) consolidation treatment in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), in order that patients remained in treatment-free remission (≥MR4.0) without molecular relapse 12 months after starting the Treatment-Free Remission (TFR) phase.

Detailed description:
This was a prospective, randomized, open-label, multicenter Phase III study. The study design was made up of 3 phases:

* Nilotinib induction phase: 12 months
* Nilotinib consolidation phase: 12 or 24 months, depending on randomization
* Nilotinib treatment-free remission (TFR) phase: 24 or 36 months, depending on randomization.

Subjects were enrolled into the study and were treated with nilotinib 300mg twice daily (BID) for 24 months, during the induction (12 months) and consolidation (12 months) phases. At the end of the first 24 months of treatment, participants achieving a sustained molecular response (defined as ≥ MR4.0, in 4 out of 5 real-time quantitative polymerase chain reaction (RQ-PCR) assessments, including the last assessment, in the last 12 months) were randomized on a 1:1 basis to either:

1. suspend nilotinib treatment immediately and enter the TFR phase for 36 months (Nilotinib 24-month treatment arm), or
2. continue nilotinib treatment for a further 12 months (post-randomization consolidation phase), then suspend treatment and enter the TFR phase for 24 months (Nilotinib 36-month treatment arm).

Participants not achieving a sustained molecular response at 24 months from treatment start were not eligible for randomization and were treated at the discretion of the investigator according to standard practice. Information on survival, stem cell transplantation, and status of the patient's disease was collected until death or until 5 years from study entry, whichever came first. Additionally, for Nilotinib 36-month treatment arm, participants who did not achieve a sustained molecular response at 36 months from treatment start, discontinued from the study and were treated according to standard practice and followed up until death or until 5 years from study entry, whichever came first.

Participants relapsing during the TFR phase entered the nilotinib re-treatment phase of the study, and were re-treated with the same dose of nilotinib as they were on before the TFR phase. These patients remained on study until the completion of the 5-year study period unless prematurely withdrawn and discontinued from the study for any reason specified in the Protocol.

Arms:
arm 1: Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase arm 2: Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase arm 3: Participants were treated with nolotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment.

Interventions: intervention 1: Nilotinib
Intervention descriptions: intervention 1: Participants received a daily oral nilotinib dose of 300 mg BID, given as two 150 mg capsules BID.

Protocol document:
Prot_000.pdf: 


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Table of contents
Table of contents .................................................................................................................2
List of figures ......................................................................................................................6
List of tables ........................................................................................................................6
List of abbreviations............................................................................................................7
Glossary of terms...............................................................................................................10
Amendment 4 (01-Jun-2016) ............................................................................................11
Summary of previous amendments ...................................................................................12
Protocol summary..............................................................................................................19
1
Background........................................................................................................................25
1.1
Overview of disease pathogenesis, epidemiology and current treatments ............25
1.2
Introduction to investigational treatment(s) and other study treatment(s).............26
1.2.1
Overview of nilotinib............................................................................26
2
Rationale............................................................................................................................30
2.1
Study rationale and purpose...................................................................................30
2.2
Rationale for the study design ...............................................................................31
2.3
Rationale for dose and regimen selection..............................................................32
2.4
Rationale for choice of combination drugs............................................................32
2.5
Rationale for choice of comparators drug .............................................................33
2.6
Rationale for optional Stem cells ENESTPath substudy.......................................33
2.7
Rationale for ‘CML patient’s voice’ Italian Substudy ..........................................33
3
Objectives and endpoints...................................................................................................34
4
Study design ......................................................................................................................39
4.1
Description of study design ...................................................................................39
4.1.1
Description of optional Stem cells ENESTPath substudy ....................40
4.1.2
Description of ‘CML patient’s voice’ Italian substudy.........................41
4.2
Timing of interim analyses and design adaptations...............................................41
4.3
Definition of end of the study................................................................................42
4.4
Early study termination..........................................................................................42
5
Population..........................................................................................................................43
5.1
Patient population..................................................................................................43
5.2
Inclusion criteria ....................................................................................................43
5.3
Exclusion criteria...................................................................................................45
6
Treatment...........................................................................................................................47
6.1
Investigational treatment, other study treatment, supportive treatment ................47
6.1.1
Dosing regimen.....................................................................................47


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6.1.2
Ancillary treatments..............................................................................47
6.1.3
Rescue medication ................................................................................47
6.1.4
Guidelines for continuation of treatment ..............................................48
6.1.5
Treatment duration................................................................................48
6.2
Dose escalation guidelines.....................................................................................48
6.3
Dose modifications................................................................................................49
6.3.1
Dose modification and dose delay ........................................................49
6.3.2
Dose-reduction guidelines for study drug-related non-hematologic 
toxicity...................................................................................................49
6.3.3
Dose-reduction guidelines for study drug-related hematologic 
toxicity...................................................................................................54
6.3.4
Suggested management of selected adverse events ..............................55
6.3.5
Guidelines for dose-re-escalation..........................................................57
6.4
Concomitant medications ......................................................................................57
6.4.1
Permitted concomitant therapy .............................................................57
6.4.2
Permitted concomitant therapy requiring caution and/or action...........58
6.4.3
Prohibited concomitant therapy ............................................................58
6.5
Patient numbering, treatment assignment and randomization...............................59
6.5.1
Patient numbering .................................................................................59
6.5.2
Treatment assignment and randomization ............................................59
6.5.3
Treatment blinding................................................................................59
6.6
Study drug supply..................................................................................................60
6.6.1
Study drug preparation and dispensation..............................................60
6.6.2
Study drug packaging and labeling.......................................................60
6.6.3
Drug supply and storage........................................................................60
6.6.4
Study drug compliance and accountability ...........................................60
6.6.5
Disposal and destruction .......................................................................61
7
Visit schedule and assessments .........................................................................................61
7.1
Study flow and visit schedule................................................................................61
7.1.1
Pre-screening assessment......................................................................78
7.1.2
Screening...............................................................................................78
7.1.3
Run-in-period........................................................................................80
7.1.4
Induction/consolidation phase...............................................................80
7.1.5
Randomization/Eligibility visit.............................................................81
7.1.6
Treatment-free remission phase............................................................83
7.1.7
Nilotinib re-treatment phase (if applicable) ..........................................84


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7.1.8
End of Phase visit, including premature withdrawal and study 
discontinuation visit ..............................................................................84
7.1.9
Follow-up period...................................................................................86
7.2
Assessment types...................................................................................................87
7.2.1
Efficacy assessments.............................................................................87
7.2.2
Safety and tolerability assessments.......................................................88
7.2.3
Pharmacokinetics ..................................................................................93
93
7.2.5
Other assessments .................................................................................93
8
Safety monitoring and reporting........................................................................................93
8.1
Adverse events.......................................................................................................93
8.1.1
Definitions and reporting ......................................................................93
8.1.2
Laboratory test abnormalities................................................................95
8.1.3
Adverse events of special interest.........................................................95
8.2
Serious adverse events...........................................................................................96
8.2.1
Definitions.............................................................................................96
8.2.2
Reporting...............................................................................................96
8.3
Emergency unblinding of treatment assignment ...................................................97
8.4
Pregnancies............................................................................................................97
8.5
Warnings and precautions......................................................................................97
8.6
Data Monitoring Committee (DMC).....................................................................97
8.7
Scientific Study Management Committee.............................................................98
9
Data collection and management.......................................................................................98
9.1
Data confidentiality ...............................................................................................98
9.2
Site monitoring ......................................................................................................99
9.3
Data collection.....................................................................................................100
9.4
Database management and quality control..........................................................100
10 Statistical methods and data analysis ..............................................................................100
10.1
Analysis sets ........................................................................................................100
10.1.1
Full Analysis Set .................................................................................100
10.1.2
Patients entering the TFR phase..........................................................100
10.1.3
Safety Set ............................................................................................101
10.1.4
Per-Protocol Set ..................................................................................101
10.1.5
Other analysis sets...............................................................................101
10.2
Patient demographics/other screening characteristics .........................................101
10.3
Treatments (study treatment, concomitant therapies, compliance) .....................101


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10.4
Primary objective.................................................................................................101
10.4.1
Variable...............................................................................................101
10.4.2
Statistical hypothesis, model, and method of analysis........................102
10.4.3
Handling of missing values/censoring/discontinuations.....................102
10.4.4
Supportive analyses.............................................................................102
10.5
Secondary objectives ...........................................................................................102
10.5.1
Key secondary objective(s).................................................................102
10.5.2
Other secondary efficacy objectives ...................................................104
10.5.3
Safety objectives .................................................................................105
10.6
Interim analysis....................................................................................................106
10.7
Sample size calculation........................................................................................106
10.8
Power for analysis of key secondary variables....................................................107
11 Ethical considerations and administrative procedures ....................................................107
11.1
Regulatory and ethical compliance......................................................................107
11.2
Responsibilities of the investigator and IRB/IEC/REB.......................................107
11.3
Informed consent procedures...............................................................................107
11.4
Discontinuation of the study................................................................................108
11.5
Publication of study protocol and results.............................................................108
11.6
Study documentation, record keeping, and retention of documents....................109
11.7
Confidentiality of study documents and patient records .....................................109
11.8
Audits and inspections.........................................................................................110
11.9
Financial disclosures............................................................................................110
12 Protocol adherence ..........................................................................................................110
12.1
Amendments to the protocol................................................................................110
13 References (available upon request)................................................................................111
14 Appendices ......................................................................................................................114
14.1
Appendix 1 List of CYP3A4 inducers and inhibitors..........................................114
14.1.1
List of medications metabolized by CYP3A4, strong, moderate and 
weak inhibitors of CYP3A4 to be used with caution..........................114
14.2
Edinburgh Claudication Questionnaire................................................................116


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List of figures
Figure 4-1
ENESTPath study design......................................................................39
Figure 4-2
Optional Stem cells ENESTPath substudy design................................41
List of tables
Table 3-1
Objectives and related endpoints ..........................................................35
Table 6-1
Dose and treatment schedule.................................................................47
Table 6-2
Summary of dose reduction guidelines for study drug-related 
clinically significant non-hematologic toxicity.....................................51
Table 6-3
Summary of dose reduction guidelines for study drug-related 
hematologic toxicity..............................................................................55
Table 6-4
Preparation and dispensing ...................................................................60
Table 6-5
Packaging and labeling .........................................................................60
Table 7-1
Visit evaluation schedule 1: screening and induction/consolidation 
phase......................................................................................................62
Table 7-2
Visit evaluation schedule 2: Nilotinib TFR phase (Arm 1) ..................71
Table 7-3
Visit evaluation schedule 3: Nilotinib TFR phase (Arm 2) ..................73
Table 7-4
Visit evaluation schedule 4: Nilotinib re-treatment phase (if 
applicable).............................................................................................76
Table 7-5
ECOG performance criteria ..................................................................90


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List of abbreviations
ABL
Abelson leukemia virus
AE
Adverse event
ALT
Alanine aminotransferase/glutamic pyruvic transaminase/GPT
ANC
Absolute neutrophil count
Anti HBc
Hepatitis B Core Antibody
AP
Accelerated phase
AST
Aspartate aminotransferase/glutamic oxaloacetic transaminase/GOT
AUC
Area under curve
BC
Blast crisis
BCR
Break point cluster region
BCR-ABL
BCR-ABL oncoprotein product of BCR-ABL fusion gene
BID
bis in diem/twice a day
CBA
Chromosome banding analysis
CCyR
Complete cytogenetic response
CgR
Cytogenetic response
Cmax
Maximum plasma concentration
CML
Chronic myeloid leukemia
CP
Chronic phase
CRO
Contract research organization
CSR
Clinical study report
CTCAE
NCI Common Terminology Criteria for Adverse Events
CV
Coefficient of variation
CVA
Cerebrovascular accident
CYP
Cytochrome P450
DDI
Drug-drug interaction
DMC
Data Monitoring Committee
DS&E
Drug Safety and Epidemiology
EC
European Commission
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
Case Report/Record Form; the term CRF can be applied to either EDC or Paper
EDC
Electronic data capture
EOP
End of phase
EOS
End of study
EUTOS
European Treatment Outcome Study
FACS
Fluorescence activated cell sorting
FAS
Full Analysis Set
FDA
Food and Drug Administration (USA)
FISH
Fluorescent in-situ hybridization
GCP
Good Clinical Practice
GI
Gastrointestinal
GP
General practitioner
HBc Ab
Hepatitis B Core Antibody
HBs Ag
Hepatitis B Surface Antigen
IB
Investigator Brochure


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ICF
Informed consent form
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IFN
Interferon
IHD
Ischemic heart disease
IN
Investigator Notification
INR
International normalized ratio
IRB
Institutional Review Board
IS
International scale
IVRS
Interactive voice response system
KM
Kaplan-Meier
LC-MS/MS
Liquid chromatography-tandem mass spectrometry
LLN
Lower limit of normal
LLOQ
Lower limit of quantification
LSC
Leukemic stem cell(s)
LVEF
Left ventricular ejection fraction
MedDRA
Medical Dictionary for Regulatory Activities
MMR
Major molecular response
MR
Molecular response
MR4.0
4.0 log reduction on international scale (IS)
MR4.5
4.5 log reduction on international scale (IS)
OS
Overall survival
PAOD
Peripheral artery occlusive disease
PCR
Polymerase chain reaction
PD
Pharmacodynamics
PFS
Progression free survival
Ph
Philadelphia chromosome
Ph+ CML
Philadelphia chromosome-positive chronic myeloid leukemia
PHI
Protected health information
PI-3 kinase
Phosphatidylinositol-3-kinases
PK
Pharmacokinetic
PPS
Per-Protocol Set
QD
Once a day
RDC
Remote data capture
REB
Research Ethics Board
RQ-PCR
Real-time quantitative polymerase chain reaction
RT-PCR
Reverse transcriptase polymerase chain reaction
RU
Resource utilization
SAE
Serious adverse event
SD
Standard deviation
SS
Safety Set
SSMC
Scientific Study Management Committee
STAT5
Signal transducer and activator of transcription 5
t1/2
Half-life
TFR
Treatment-free remission
TFS
Treatment-free survival
TKI
Tyrosine kinase inhibitor


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ULN
Upper limit of normal
VAP
Validation and Planning
WBC
White blood cell
WOCBP
Women of childbearing potential


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Glossary of terms
CHR
Complete hematologic response = normalization of hematopoiesis
CCyR
Complete cytogenetic response = 0% Ph+ metaphases in a review of a minimum of 20 
metaphases in the bone marrow
MMR
Major Molecular Response, MMR is defined as a ≥3.0 log reduction in BCR-ABL transcripts 
compared to the standardized baseline or ≤ 0.1% BCR-ABL according to the international 
scale as measured by RQ-PCR
MR4.0
Defined as either (i) detectable disease ≤0.01% BCR-ABL IS; or (ii) undetectable disease in 
cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of 
cDNA used to test for BCR-ABL)
MR4.5
Defined as either (i) detectable disease ≤0.0032% BCR-ABL IS; or (ii) undetectable disease 
within cDNA with ≥32,000 ABL transcripts (numbers of ABL transcripts in the same volume 
of cDNA used to test for BCR-ABL)
MR 5
Defined as either (i) BCR-ABL (IS) ≤0.001%; or (ii) undetectable disease with Total ABL 
≥100.000
Assessment
A procedure used to generate data required by the study
Control drug
A study treatment used as a comparator to reduce assessment bias, preserve blinding of 
investigational drug, assess internal study validity, and/or evaluate comparative effects of the 
investigational drug
Enrollment
Point/time of patient entry into the study; the point at which informed consent must be 
obtained (i.e. prior to starting any of the procedures described in the protocol)
Investigational 
drug
The study treatment whose properties are being tested in the study; this definition is 
consistent with US CFR 21 Section 312.3 and is synonymous with “investigational new drug”
Investigational 
treatment
Drug whose properties are being testing in the study as well as their associated placebo and 
active treatment controls (when applicable). This also includes approved drugs used outside 
of their indication/approved dosage, or that are tested in a fixed combination. Investigational 
treatment generally does not include other study treatments administered as concomitant 
background therapy required or allowed by the protocol when used in within approved 
indication/dosage
Medication 
number
A unique identifier on the label of each study treatment package which is linked to one of the 
treatment groups of a study
Other study 
treatment
Any drug administered to the patient as part of the required study procedures that was not 
included in the investigational treatment
Subject Number 
(Subject No.)
A unique identifying number assigned to each patient/healthy volunteer who enrolls in the 
study
Period
A subdivision of the study timeline; divides stages into smaller functional segments, such as 
screening, baseline, titration, washout, etc.
Premature patient 
withdrawal
Point/time when the patient exits from the study prior to the planned completion of all study 
treatment administration and/or assessments; at this time all study treatment administration 
is discontinued and no further assessments are planned, unless the patient will be followed 
for progression and/or survival
Randomization 
number
A unique treatment identification code assigned to each randomized patient, corresponding 
to a specific treatment arm assignment
Stage related to 
study timeline
A major subdivision of the study timeline; begins and ends with major study milestones such 
as enrollment, randomization, completion of treatment, etc.
Stop study 
participation
Point/time at which the patient came in for a final evaluation visit
Study treatment
Includes any drug or combination of drugs in any study arm administered to the patient 
(subject) as part of the required study procedures, including placebo and active drug run-ins.
In specific examples, it is important to judge investigational treatment component relationship 
relative to a study treatment combination; study treatment in this case refers to the 
investigational and non-investigational treatments in combination.


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Amendment 4 (01-Jun-2016)
Amendment rationale
The recruitment of this study has been completed (LPFV 30-Apr-2015) and 621 patients have 
been enrolled.
The primary purpose for the amendment is:

To include hepatitis B virus testing as one of the study procedures, to identify study 
patients who may be at risk of hepatitis B reactivation. Reactivation of hepatitis B virus 
can occur in patients who are chronic carriers of this virus and are receiving a drug of the 
BCR-ABL TKI class such as nilotinib. Some cases involving BCR-ABL TKI resulted in 
acute hepatic failure or fulminant hepatitis leading to liver transplantation or a fatal 
outcome.
Changes to protocol
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underline for insertions.

List of abbreviations updated.

Protocol Summary was updated to add serology in the panel of Safety assessments.

Section 6.3.4 Hepatitis B reactivation was added to provide information on next steps for 
patients tested positive for hepatitis B virus.

Section 7-1 Hepatitis B testing was added to the visit schedule to be performed once and 
only once at the next possible visit when patient is on treatment or before treatment is re-
initiated.

Section 7.2.2.4.5 Hepatitis B testing was added to provide information on hepatitis B 
testing.

Section 8.6 Data Monitoring Committee (DMC) regular and specific reports have been 
updated

Section 10.6 Interim analysis minor update

All other sections, to correct minor inconsistencies and typos
IRBs/IECs
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities.
The changes herein affect the Informed Consent. Sites are required to update and submit for 
approval a revised Informed Consent that takes into account the changes described in this 
protocol amendment.


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Summary of previous amendments
Amendment 3
Amendment Rationale
The primary purpose for this substantial amendment is:

To update the protocol with the latest changes in the Investigator Brochure Edition 11.

To update the protocol including the ‘CML patient’s voice’ Italian substudy to evaluate 
the emotional aspects in patients participating to a nilotinib Treatment-free remission 
(TFR) trial. This substudy aims to examine patients’ psycho-emotional characteristics, 
quality of life and experiences of being involved in CAMN107AIC05 trial and its 
discontinuation using a qualitative-quantitative mixed method. The ‘CML patient’s voice’
Italian substudy will be conducted in Italy only. It will be coordinated by the Chair of 
Clinical Psychology, San Paolo Hospital, University of Milan. Further details can be 
found in the Post Text Supplement 1.
Changes to the protocol

Section 1.2.1.1: Updated with the mouse carcinogenicity study

Section 2.7: Updated with the rationale of the ‘CML patient’s voice’ Italian substudy

Section 4.1.2: Updated with the Italian ‘CML patient’s voice’ Italian substudy

Section 5.4 and Section 5.5: Updated with the inclusion and exclusion criteria for the 
‘CML patient’s voice’ Italian substudy

Sections 6.4.2 and 6.4.3 are updated with the information on permitted concomitant 
therapy (CYP3A4 and Antacid drugs)

Section 11.3: ICF procedure updated with safety data from pre-clinical study

All other sections: minor typos corrections

Addition of references to support rationale for ‘CML patient’s voice’ Italian substudy

IRB/IECA copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities.

Appendix 14.1.1 (List of medications metabolized by CYP3A4, strong, moderate and 
weak inhibitors of CYP3A4 to be used with caution) is updated.


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Amendment 2
Amendment rationale
The primary purpose for this substantial amendment is:

To modify the study sample size based on new data from the ENESTcmr and STIM 
studies and a number of recently published clinical trials (Hughes TP, et al. Blood. 
2014;124: 729-36; Mahon FX, et al. Blood. 124(21);151; Rea D, et al. Blood. 
2014;124(21) [abstract 811])

To amend the secondary objectives of the study and related endpoints

To incorporate the safety recommendations provided by the DMC on patients with severe 
cardiovascular ischemic events experienced before entering the study or while on study
i.e.:

Patients with prior PAOD, or severe ischemic cardiovascular disease for whom in the 
opinion of the investigator other treatments might have a more favorable benefit/risk 
profile will be excluded from the study

Patients who experience severe Ischemic vascular or cardiovascular events have to be 
discontinued from the study whenever in the opinion of the investigator the AE is 
related to the study drug and other treatments could have a more favorable benefit/risk 
profile

To update the efficacy and safety data of nilotinib according to the Investigator’s Brochure 
Edition 10 (April 2014)

To implement requests of Health Authorities and Ethics Committees/Institutional Review 
Boards (ECs/IRBs) raised during review of the protocol version number 01

To update the visit numbering according to the new eCRF design

To correct minor inconsistencies and typos in the protocol
Changes to the protocol

Table 3-1: Update of secondary objectives and related endpoints

Section 4.1: Update of sample size

Figure 4-1: update of visit numbering

Section 4.1.1: Addition of time point for determination of PH+ stem cells in bone marrow
for patients enrolled in the optional Stem cells ENESTath substudy

Section 4.2: Addition of information about publication of results

Section 5.2: Corrections of inclusion criteria numbering and other minor corrections

Section 5.3: Update of exclusion criteria relating to history PAOD or severe ischemic 
cardiovascular disease; deletion of refusal to give consent for the optional Stem cells 
ENESTath substudy from exclusion criteria for main study

Table 6-2: Update QTc criteria for study discontinuation; update of action to be taken for 
grade 3 or 4 ischemic vascular or cardiovascular events; update of action to be taken for 
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
Table 7-1, Table 7-2, Table 7-3, and Table 7-4: Update of assessments schedule and 
numbering

Section 7.1.4: Clarification and update of assessments to be done during the induction 
/consolidation phase

Section 7.1.5: Clarification on procedures to be done at the randomization and at 
eligibility visits

Section 7.1.6: Update of action patient to take with remaining study drug

Section 7.1.7: Clarification of procedures to be done during the re-treatment phase

Section 7.1.8: Update of EOP visits definition

Section 7.1.8.1: Update of criteria for premature patient withdrawal

Section 7.2.1.1: Update of methodology to be used to assess molecular response according 
to the latest EUTOS working guidelines

Section 7.2.1.3: Clarification of when CgR assessment should be performed

Section 7.2.2.4.4: Update of when urine analysis is to be performed

Section 7.2.2.7: Clarification of when the questionnaire is to be administered and action to 
be taken if questionnaire results are positive

Section 8.1.1: Update of when adverse event monitoring is to be done

Section 8.6: Added information about timing of DMC meetings

Section 10.4.2: Amendment of statistical hypotheses based on new assumptions

Section 10.4.3: Update of method to handle missing values

Section 10.5.1: Amendment of the secondary endpoints and corresponding statistical 
methods

Section 10.5.2: Amendment of the statistical methods to be applied for the Stem cells 
ENESTPath substudy.

Section 10.7: Amendment of assumptions used for sample size calculation for main study 
and Stem cells substudy

All other sections: minor typos corrections


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Amendment 1
Amendment rationale
The primary purpose for this substantial amendment is:

Inclusion of the optional Stem cells ENESTpath substudy “Leukemic stem cells 
quantification in patients with chronic myeloid leukemia included in the ENESTpath trial”;
the purpose of this substudy is to evaluate the importance of leukemic stem cells (LSC) in 
the long-term maintenance of the disease and their role in the relapse of patients during the 
TFR phase. Participation in this “stem cells" substudy is optional and requires separate 
specific consent. Patients not wishing to participate in the stem cells substudy may still 
participate in the main (ENESTpath) study

To update the efficacy and safety data of nilotinib according to the Investigator’s Brochure 
Edition 9 (June 2013), focusing on the 48-month update of the CAMN107A2303 study in 
newly diagnosed CML-CP patients

To include cholesterol testing in the assessment schedule. Elevations in total serum 
cholesterol and low density lipoprotein cholesterol have been observed very commonly in 
patients treated with nilotinib or imatinib. Most of the cholesterol elevations were grade 1 
(> ULN - 300 mg/dL; > ULN - 7.75 mmol/L) or 2 (> 300 - 400 mg/dL; > 7.75 - 10.34 
mmol/L), and some elevations were present prior to initiation of CML therapy. Lipid 
profiles, including total cholesterol, LDL-C and HDL-C will be assessed at baseline and
during the conduct of this study. If test results warrant intervention, investigators should 
follow their local standards of practice or treatment guidelines, which may recommend 
treatment even for grade 1 cholesterol elevation. Before prescribing a lipid-lowering 
medication, the possibility of drug-drug interactions should be considered as some HMG-
CoA reductase inhibitors are also metabolized via the CYP3A4 pathway

To include glucose testing in the assessment schedule. Elevations of blood glucose levels 
have been observed in CML patients treated with nilotinib. Blood glucose will be assessed 
at baseline and during the conduct of this study. If test results warrant intervention, 
investigators should follow their local standards of practice and treatment guidelines

To provide a harmonization on dose reductions guidelines across Novartis-sponsored 
Tasigna study protocols

To incorporate guidance for the management of:

Serum cholesterol increases

Blood glucose increases

Other cardiac risk factors

Ischemic vascular or ischemic cardiovascular events occurring in patients treated with 
nilotinib

To define ischemic vascular and ischemic cardiovascular events as adverse events of 
special interest, and their reporting


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
To implement modifications as requested from different Health Authorities and Ethics
Committees/Institutional Review Boards (ECs/IRBs) during review of the original
protocol

To address feedback from investigators received during the study startup

To correct minor inconsistencies and typos in the protocol
Changes to the protocol
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol, and include the following:

Section 1.2.1.2.1: Addition of a session on “Ischemic Vascular and Ischemic 
Cardiovascular Events Reported for CAMN107A2303 (ENESTnd Study)”

Section 2.6: New section providing rationale for optional Stem cells ENESTpath substudy 
included in Protocol Amendment 1

Section 3: Addition of objectives, endpoints, and analyses for optional Stem cells 
ENESTpath substudy included in Protocol Amendment 1

Section 4.1: Addition of visit/month information to Figure 4-1 to improve clarity

Section 4.1.1: Addition of new subsection with study description for the optional Stem 
cells ENESTpath substudy included in Protocol Amendment 1

Section 4.4: Changes to early study termination criteria

Section 5.1: Update of screening criteria for patient population, and addition of details of 
patient population for the optional Stem cells ENESTpath substudy

Section 5.2: Update of definition of chronic phase CML, update of inclusion criterion for 
patients in treatment with imatinib for a minimum of 24 calendar months (even not 
continuously) and in imatinib treatment at time of enrolment, and addition of requirement 
for separate specific informed consent for the optional Stem cells ENESTpath substudy

Section 5.3: Addition/amendment of the following exclusion criteria:

Definition of atypical BCR-ABL transcripts

Previous anticancer agents for CML except for imatinib, and/or for cytoreduction 
after CML diagnosis, and/or interferon treatment whose duration was shorter than
1 year

Known impaired cardiac function, including any of the following:

Inability to determine the QT interval on electrocardiogram [ECG]

Complete left bundle branch block

Right bundle branch block plus left anterior or posterior hemiblock

Use of a ventricular-paced pacemaker

Congenital long QT syndrome or a known family history of long QT syndrome;

History of or presence of clinically significant ventricular or atrial 
tachyarrhythmias

Clinically significant resting bradycardia (< 50 beats per minute)


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
QTc > 450 msec on the average of three serial baseline ECGs (using the QTcF 
formula). If QTcF > 450 msec and electrolytes are not within normal ranges, 
electrolytes should be corrected and the patient re tested for the QTc

History of clinically documented myocardial infarction within 1 year prior to 
study entry

History of unstable angina during the last 12 months

Other clinically significant heart disease (e.g. congestive heart failure or 
uncontrolled hypertension)

Severe and/or uncontrolled concurrent medical disease that in the opinion of the 
investigator could cause unacceptable safety risks or compromise compliance with the 
protocol (e.g. atherothrombotic events [such as ischemic heart disease, peripheral 
arterial occlusive disease, symptomatic carotid stenosis/cerebrovascular accident 
(CVA)], uncontrolled diabetes, active or uncontrolled infection, uncontrolled severe 
hypertension, or uncontrolled severe dyslipidemia). If appropriate measures (e.g. diet, 
exercise, appropriate therapy) are taken to control blood glucose, or cholesterol LDL 
levels, or hypertension, the patient can be re-screened for the study

Unwillingness to use specified highly efficient forms of contraception in women of
childbearing potential (WOCBP)

Refusal to provide separate specific consent for the optional Stem cells ENESTpath 
substudy included in Protocol Amendment 1 (eligibility for the main ENESTpath 
study remains unaffected)

Section 6.3: Amendment of dose modification guidelines, and in Section 6.3.2: 
Amendment of dose reduction guidelines to include ischemic vascular or cardiovascular 
events, and arrhythmical cardiac toxicity

Section 6.3.4: Update of suggested management of selected adverse events

Section 6.4.2: Update to permitted concomitant therapy to include management of 
hyperglycemia and/or hypertriglyceridemia in some patients

Section 6.4.3: Update to prohibited concomitant therapy

Section 7: Addition of assessments in flowcharts and assessments subsections (Edinburgh 
Claudication Questionnaire, smoking history, and family history of cardiovascular events, 
urine pregnancy tests, HbA1C, HDL and LDL, microalbuminuria, determination of Ph+ 
stem cells in bone marrow); addition of two extra optional visits (Day 15 and Month 1 in 
first trimester of induction/consolidation phase) for hematology/clinical chemistry 
assessments, plus renumbering of all subsequent visits

Section 7.1.1: Amendment of screening assessments to include the decision tree for 
protocol entry based on the molecular response

Section 7.1.7.1: Expansion of withdrawal criteria relating to pregnancy (occurring during 
nilotinib treatment or during TFR phase or within 30 days of last dose of nilotinib)

Section 7.2.2.1: Update of the “Physical Examination” section with the addition of the
extramedullary involvement

Section 7.2.2.4.2: Update of clinical chemistry

Section 7.2.2.4.3: Update of pregnancy assessments according to the IB Edition 9


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
Section 7.2.2.7: Addition of a section regarding the Edinburgh Claudication Questionnaire

Section 7.2.5: Addition of bone marrow assessments for patients who participate in the 
Stem cells ENESTpath substudy

Section 8.1.3: Addition of a section regarding adverse events of special interest (ischemic 
vascular and cardiovascular events)

Section 8.4: Expanded statements about pregnancy

Section 8.6: Changes to data monitoring committee constitution and possible DMC 
recommendations

Section 10.1: Update of the “Analysis sets” section

Section 10.5.1: Update of key secondary objectives

Section 10.5.2: Addition of secondary objectives for optional Stem cells ENESTpath 
substudy

Section 10.5.3: Update of safety objectives

Section 10.7: Addition of sample size calculation for optional Stem cells ENESTpath 
substudy

Section 11.3: Addition of specific informed consent for optional Stem cells ENESTpath 
substudy

Section 11.5: Adaptation of authorship rules to comply with SSMC charter

Addition of references to support rationale for optional Stem cells ENESTpath substudy

Addition of Appendix containing the lists of CYP3A4 inducers and inhibitors and the 
Edinburgh Claudication Questionnaire

Changes to protocol summary to match main protocol

Minor changes and corrections for clarity
IRB/IEC
A copy of this amended protocol will be sent to the Institutional Review Board
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities.


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Protocol summary
Protocol number
AMN107AIC05
Title
A prospective, randomized, open-label, two-arm Phase III study to evaluate treatment-
free remission (TFR) rate in patients with Philadelphia chromosome-positive CML after
two different durations of consolidation treatment with nilotinib 300 mg BID
Brief title
A randomized phase III study to assess the effect of a longer duration of consolidation 
treatment with nilotinib on TFR in patients with CML in the chronic phase (CML-CP)
Sponsor and
Clinical Phase
Novartis
Phase III
Investigation type
Drug
Study type
Interventional
Purpose and 
rationale
Purpose:
This study aims to assess the optimal duration of nilotinib 300 mg twice daily (BID, bis in 
die) consolidation treatment, in order that patients remain in TFR (≥molecular response 
[MR]4.0) 12 months after starting the TFR phase of the study.
Rationale:
The natural history of chronic myeloid leukemia (CML) was changed dramatically by the 
introduction of TKIs (tyrosine kinase inhibitors), which have increased patient survival 
and consequently have prolonged the duration and increased the prevalence of the 
disease. It is estimated that the number of CML cases will continue to increase over the 
next half century, with the number of patients expected to exceed 250,000 in the USA 
alone. In this context, TFR studies may serve to both provide a new treatment paradigm 
for patients (in respect to the minimization of drug-drug interactions, elimination of 
chronic side effects, and benefit of pregnancy without exposure to TKIs), and also 
potentially have a positive impact on health economics, considering the expected 
increase in the numbers of patients with the disease.
CML-CP patients who have received 24 or more months of first-line imatinib treatment, 
and who have failed to achieve the molecular response threshold for treatment cessation 
(equal to or more than MR4.0, ≥MR4.0) have a 50% greater chance of achieving this level 
of molecular response by switching to nilotinib; however, the optimal duration of 
consolidation treatment with nilotinib to ensure the highest rate of patients remaining in 
≥MR4.0 after suspending treatment is not yet known. This protocol therefore aims to 
assess the potential impact of two durations of consolidation treatment with nilotinib, i.e. 
12 months versus 24 months, on molecular relapse rate in the first 12 months of the TFR
phase.
Rationale for optional Stem cells ENESTPath substudy - “Leukemic stem cells 
quantification in patients with chronic myeloid leukemia included in the ENESTPath trial”: 
The focus of this optional Stem cells ENESTPath substudy is to evaluate the importance 
of leukemic stem cells (LSC) in the long-term maintenance of the disease and their role 
in the relapse of patients during the TFR phase. This optional Stem cells ENESTPath 
substudy evaluates:
●
The presence and number of LSC and their progenitors in the bone marrow of all 
patients participating in this substudy before and after completing induction and the first 
year of the consolidation phase (at Visit 8).
●
Whether prolonging the treatment period of consolidation with nilotinib (patients in 
Arm 2) induces a reduction in the percentage of patients presenting LSC and progenitor 
cells in bone marrow at the end of the second year of the consolidation phase.
Rationale of ‘CML patient’s voice’ Italian substudy - The inner psycho-emotional 
experiences of CML patients during consolidation and TFR phases are unknown.The 
‘CML patient’s voice’ Italian substudy aims to examine patients’ psycho-emotional 
characteristics, quality of life and experiences of being involved in the ENESTPath study
and its discontinuation using a mixed method design qualitative-quantitative. This
substudy will be conducted in Italy only. For further details, please refer to the [Post-text 
Supplement 1]


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Primary objective
To assess the optimal duration of consolidation treatment with nilotinib 300 mg BID in 
order that patients remain in treatment-free remission (≥MR4 0) without molecular relapse 
12 months after entering the TFR phase
Secondary 
objectives
●
To evaluate the proportion of patients who are eligible to suspend nilotinib therapy by 
achieving and maintaining sustained ≥MR4 0 for at least 12 months during consolidation 
treatment with 300 mg BID nilotinib
●
To assess the achievement of MMR, MR4 0, and MR4 5 during induction/consolidation 
treatment with nilotinib 300 mg BID at the different time points in patients without that 
response at study entry
●
To assess the molecular response in patients during induction/consolidation 
treatment with nilotinib 300 mg BID at the different time points
●
To assess the proportion of patients in TFR at 3, 6, 12, 18, and 24 months after 
nilotinib cessation in the two treatment arms
●
To assess the molecular response in patients after randomization in the two 
treatment arms
●
To assess the kinetics of BCR-ABL transcript during induction/consolidation 
treatment with 300 mg BID nilotinib, during the TFR phase and during the nilotinib re-
treatment phase.
●
To assess the progression-free survival (PFS) rate after randomization in both 
treatment arms
●
To assess the treatment-free survival (TFS) rate after the start of TFR phase in the 
two treatment arms
●
To assess the overall survival (OS) rate after randomization in the two treatment 
arms
●
To assess the safety profile of nilotinib during the induction/consolidation phase, the 
TFR phase, and the re-treatment phase
For those patients consenting to participate in the optional Stem cells ENESTPath 
substudy, the following objectives will be also evaluated:
●
To evaluate the presence and number of LSC and their progenitors in the bone 
marrow before and after completing induction and the first year of the consolidation 
phase (at Visit 8);
●
To evaluate whether prolonging the treatment period of consolidation with nilotinib 
(patients in Arm 2 versus patients in Arm 1) induces a reduction in the percentage of 
patients presenting LSC and progenitor cells in bone marrow at the end of the second 
year of the consolidation phase (Visit 204 for Arm 2 versus Visit 8 for Arm 1).
●
To perform an exploratory analysis in order to evaluate whether relapse in patients 
during the TFR phase in either arm correlates with the presence of LSC and progenitor 
cells in bone marrow at the end of consolidation phase and at the time of relapse during 
TFR
For those patients consenting to participate to the ‘CML patient’s voice’ Italian substudy, 
please refer to the [Post-text Supplement 1].


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Study design
This is a prospective, randomized, open-label, multicenter, two-arm Phase III study that 
includes a 12-month induction phase, followed by a 12 or 24-months consolidation phase 
(dependent on randomization) and a 36 or 24-months TFR phase, respectively, totaling a 
5-year study duration for the individual patient.
Eligible patients are adults with a confirmed diagnosis of CP Philadelphia chromosome-
positive (Ph+) and/or BCR-ABL+ CML who have been treated with first-line imatinib for 
24 months or more, and are in complete cytogenetic response (CCyR). Patients must not 
have achieved ≥MR4.0 at study entry, as assessed by a EUTOS laboratory.
Approximately 565 patients will be enrolled into the study and will be treated with nilotinib 
300 mg BID for 24 months. Following 24 months of treatment, patients in sustained 
molecular response for at least the last 12 months will be randomized on a 1:1 basis to 
either:
●
Suspend nilotinib treatment immediately and enter the TFR phase (Arm 1; the 
nilotinib 24-month treatment arm), or
●
Continue nilotinib treatment for a further 12 months then suspend treatment and 
enter the TFR phase (Arm 2; the nilotinib 36-month treatment arm).
Patients not achieving a sustained molecular response at 24 months (and subsequently 
at 36 months if previously randomized to the treatment arm with 1 year additional 
consolidation) will exit the study and will be treated at the discretion of the investigator 
according to standard practice. Information on survival, stem cell transplant, and the 
status of the patient’s disease (i.e. disease progression to AP (accelerated phase)/BC 
(blast crisis) according to protocol definition, TKI treatment) will be collected until death, 
or until 5 years from study entry, whichever comes first.
Patients relapsing during the TFR phase will enter the nilotinib re-treatment phase of the 
study, and will be re-treated with the same dose of nilotinib as they were on before the 
TFR phase (i.e. the re-treatment dose will be nilotinib 300 mg BID or a lower dose of 
nilotinib if the dose was reduced in the consolidation phase before entering the TFR
phase).
These patients will remain on study until the completion of the 5-year study period
Optional Stem cells ENESTPath substudy:
The Stem cells ENESTPath substudy adds the determination of Ph+ stem cells in bone 
marrow in those patients consenting to participate in this substudy, at the following time 
points:
a)
At the screening visit, before starting nilotinib treatment
b)
After 2 years of nilotinib treatment at Visit 8
c)
After 3 years of nilotinib treatment, only in patients with 2 years’ consolidation 
treatment (Arm 2) at Visit 204
d)
If the patient relapses during the TFR phase, before re-starting the treatment 
with nilotinib
A 10 mL bone marrow sample will be collected and sent to 
 
 for immunophenotype analysis, FACS 
(fluorescence activated cell sorting) cell purification, in situ hybridization, and RT-PCR. 
Measurement and quantification will be performed by flow cytometry in a bone marrow 
purified population of stem cells in order to detect the presence of leukemic Ph+ cells or 
BCR-ABL transcript levels (evaluated by fluorescent in situ hybridization [FISH] or RT-
PCR).
‘CML patients’ voice’ Italian substudy:
Please refer to the [Post-text Supplement 1]


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Key inclusion 
criteria
●
Male or female patients, aged ≥ 18 years
●
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
●
Confirmed diagnosis of Ph+ and/or BCR-ABL+ CML-CP
●
Previous first-line treatment with imatinib for a minimum of 24 months (even not 
continuously) in total and in imatinib treatment at time of enrollment
●
Patient in CCyR
For those patients consenting to participate in the optional Stem cells ENESTPath 
substudy, the same inclusion criteria as for the main ENESTPath study will be 
applicable, plus the following:
●
A separate specific written informed consent for the Stem cells ENESTPath substudy 
must be obtained prior to extraction of additional bone marrow samples.
For those patients consenting to participate in the ‘CML patient’s voice’ Italian substudy , 
the same inclusion inclusion criteria as for the main ENESTPath study will be applicable.
This substudy will be conducted in Italy only.
Key exclusion 
criteria
●
Achievement of ≥MR4 0 at study entry as assessed by a EUTOS standardized 
laboratory
●
Previous treatment with BCR-ABL inhibitors other than imatinib
●
Patients with detectable atypical BCR-ABL transcripts, defined as absence of typical 
BCR-ABL transcripts for CML of the types b2(e13)-a2 or b3(e14)-a2 or both of them 
simultaneously documented at CML diagnosis or at any time before the screening 
procedure
●
Previous anticancer agents for CML except:
●
imatinib, and/or
●
cytoreduction after CML diagnosis, and/or
●
interferon for less than 1 year
●
Known second chronic phase of CML after previous progression to AP/BC;
●
Known impaired cardiac function, including any of the following:
●
Inability to determine the QT interval on ECG
●
Complete left bundle branch block
●
Right bundle branch block plus left anterior or posterior hemiblock
●
Use of a ventricular-paced pacemaker
●
Congenital long QT syndrome or a known family history of long QT syndrome
●
History of or presence of clinically significant ventricular or atrial
tachyarrhythmias
●
Clinically significant resting bradycardia (< 50 beats per minute)
●
QTc > 450 msec on the average of three serial baseline ECG (using the QTcF 
formula). If QTcF > 450 msec and electrolytes are not within normal ranges, 
electrolytes should be corrected and the patient re-tested for the QTc 
●
History of clinically documented severe PAOD or severe ischemic 
cardiovascular disease (e.g. myocardial infarction, ischemic cerebral vascular 
disease) whenever in the opinion of the investigator other treatments could have a 
more favorable benefit/risk profile.
●
Other clinically significant heart disease (e.g. congestive heart failure or 
uncontrolled hypertension)
●
Severe and/or uncontrolled concurrent medical disease that in the opinion of the 
investigator could cause unacceptable safety risks or compromise compliance with the 
protocol (e.g. uncontrolled diabetes, active or uncontrolled infection, uncontrolled severe 
hypertension, uncontrolled severe dyslipidemia). If appropriate measures (e.g. diet, 
exercise, appropriate therapy) are taken to control blood glucose or cholesterol LDL 
levels, or hypertension, the patient can be re-screened for the study.
●
History of acute pancreatitis within 12 months of study entry, or a medical history of 
chronic pancreatitis


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●
Known presence of significant congenital or acquired bleeding disorder unrelated to 
cancer
●
History of other active malignancies within 5 years prior to study entry, with the 
exception of previous or concomitant basal cell skin cancer, or previous cervical 
carcinoma in situ treated curatively 
●
Patients who have not recovered from prior surgery
●
Treatment with other investigational agents within 30 days of Day 1
●
Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers or 
medications that have the potential to prolong the QT interval that cannot be either 
discontinued or switched to a different medication prior to starting study drug
●
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter 
the absorption of study drug
●
Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential 
without a negative pregnancy test prior to baseline, or (d) of childbearing potential 
unwilling to use highly effective contraceptive precautions (as detailed below) throughout 
the trial (post-menopausal women must be amenorrheic for at least 12 months to be 
considered of non-childbearing potential)
●
Women of child-bearing potential (WOCBP), defined as all women physiologically 
capable of becoming pregnant, unless they are using highly effective methods of 
contraception during dosing and for 14 days after the final dose of nilotinib or imatinib. 
Patients using an oral hormonal contraception method should complete their monthly 
treatment course. Highly effective contraception methods include:
I.
Total abstinence (when this is in line with the preferred and usual lifestyle of the 
subject). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception
II.
Female sterilization (surgical bilateral oophorectomy with or without 
hysterectomy) or tubal ligation at least 6 weeks before taking study treatment. In 
case of oophorectomy alone, only when the reproductive status of the woman has 
been confirmed by follow-up hormone level assessment
III.
Male sterilization (at least 6 months prior to screening). For female subjects on 
the study, the vasectomized male partner should be the subject’s sole partner
IV.
Combination of any two of the following (a+b or a+c or b+c) listed below:
a)
Use of oral, injected, or implanted hormonal methods of contraception 
or other forms of hormonal contraception that have comparable efficacy (failure 
rate < 1%), e.g. hormone vaginal ring or transdermal hormone contraception
b)
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
c)
Barrier methods of contraception: condom or occlusive cap 
(diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal 
suppository 
In case of use of oral contraception, women should have been stable on the same pill for 
a minimum of 3 months before taking study treatment
●
Patients not able to understand and comply with study instructions and requirements
For those patients consenting to participate in the optional Stem cells ENESTPath
substudy, the same exclusion criteria as for the main ENESTPath study will apply
For those patients consenting to participate in the ‘CML patient’s voice’ Italian substudy, 
the same exclusion criteria as for the main ENESTPath study will apply. This substudy 
will be conducted in Italy only.
Investigational 
therapy
Nilotinib 300 mg BID
Efficacy 
assessments
●
Molecular Response (RQ-PCR, optional mutational analysis)
●
Bone marrow assessments and cytogenetics, including evaluation of LSC and 
progenitor cells in the optional Stem cells ENESTPath substudy


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Safety assessments
●
Physical examination
●
Vital signs
●
ECOG performance status
●
Laboratory evaluations (clinical chemistry, hematology, urine analysis);
●
Serology (Hep B)
●
ECG
●
Echocardiography
●
Edinburgh Claudication Questionnaire
●
Adverse events
●
Concomitant medication
●
Serum and urine pregnancy test (for WOCBP)
Other assessments
Optional Stem cells ENESTPath substudy:
●
Presence of Ph+ LSC in bone marrow (CD34+/CD38+ progenitor cells, 
CD34+/CD38−stem cells, and CD34+/CD56+ aberrant stem cells [the last ones only if 
detectable])
●
Percentage of total CD34+ cells
●
Percentage of Ph+ cells evaluated by FISH
●
BCR-ABL transcript levels on sorted cells by RT-PCR
●
Percentage of subpopulations (CD34+/CD38+, CD34+/CD38−, and CD34+/CD56+ [if 
detectable]) 
Data analysis
Based on new data from the ENESTcmr study, it is expected that 40% of the patients 
switched from imatinib to nilotinib will achieve MR4.0 or better at the end of the 12-month 
induction phase, and will maintain this level of molecular response by the end of the 12-
month consolidation phase prior to randomization. Furthermore, if the patients treated 
with nilotinib for 24 months before entering the TFR phase (Arm 1) have a similar relapse 
rate as the patients in the STIM trial (Mahon et al 2011), it is expected that 40% of 
patients randomized to Arm 1 will not have relapsed after the 12 months TFR phase. 
Based on new information from a number of recently published studies (Hughes TP et al 
2014 Blood;124:729-36; Mahon FX et al 2014 Blood;124(21):151; Rea D et al 2014
Blood.;124(21) [abstract 811]), it is reasonable to assume that a 12-month longer 
consolidation period with nilotinib (Arm 2) may reduce the molecular relapse rate in the 
first 12 months TFR phase by approximately 20% (from 60% to 40%, absolute difference 
of 20%).
Therefore it is assumed that the percentage of patients without relapse will be 40% in 
Arm 1, and 60% in the Arm 2. Considering this, a sample size of 107 patients per group 
(a total of 214) is needed to detect such a difference. These calculations are based on a 
two-sided chi-square test at 0.05 alpha level with a power of 80%. Assuming that 5% of 
patients will be unevaluable after randomization, a total of 226 patients will need to be 
randomized in order to adequately power the study. Finally, as explained above, 
assuming that 40% of the patients switched from imatinib to nilotinib will achieve ≥MR4.0
at the end of the 12-month induction phase, and will maintain this level of molecular 
response by the end of the 12-month consolidation phase prior to randomization, a total 
of 565 patients are required for this study.
Primary analysis: The proportion of patients who are in TFR (≥MR4.0) without molecular 
relapse at the end of 12 months in the TFR phase will be calculated by dividing the 
number of patients who remain in ≥MR4.0 at the end of 12 months in the TFR phase 
(without re-starting nilotinib therapy) by the number of patients who entered the TFR 
phase. A chi-square test will be applied to compare the two treatment arms. A two sided 
test with alpha = 0.05 will be used. The rate of successful TFR will be presented together 
with an exact 95% Clopper Pearson confidence interval. 
No formal interim analyses are planned.
Key words
Phase III, two-arm, open-label, nilotinib, treatment-free remission, sustained MR4.0, stem 
cells, confirmed loss of M R4.0, loss of MMR, Ph+ CML-CP.


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1
Background
1.1
Overview of disease pathogenesis, epidemiology and current 
treatments
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder of transformed, 
primitive hematopoietic progenitor cells. The hallmark of CML is the Philadelphia (Ph) 
chromosome, which is found in up to 95% of patients. It results from a reciprocal 
translocation t(9;22)(q34;q11), which adds a 3' segment of the ABL gene on chromosome 9 to 
the 5' part of the breakpoint cluster region (BCR) gene on chromosome 22. The resulting 
fusion gene encodes for a constitutively active tyrosine kinase, the BCR-Abelson (ABL)
tyrosine kinase (Faderl et al 1999), which has activity that imparts growth advantage to 
leukemic cells, increases proliferation and cytokine-independent growth, inhibits apoptosis, 
and inhibits alternate adhesion pathways (Sawyers 1999; Deininger 2000; van Etten 2004).
Clinically, CML progresses through three distinct phases of increasing refractoriness to 
therapy: chronic phase (CP; median duration 3 to 4 years; median survival up to 10 years with 
allogeneic bone marrow transplant, and 5 to 6 years with interferon), accelerated phase (AP; 
median duration 3 to 9 months; median survival 8 to 18 months), and blast crisis (BC; median 
survival 3 to 6 months) (Enright and McGlave 2000). Most patients, however, present in the 
CP, characterized by splenomegaly and leukocytosis with generally few symptoms.
The objectives of CML-CP treatment are the normalization of hematopoiesis (complete 
hematologic response), the elimination of the Ph+ cells from the bone marrow (complete 
cytogenetic response [CCyR]), and the reduction of the BCR-ABL transcript levels from 
samples of peripheral or bone marrow blood by a factor of 3.0 logs compared to the 
standardized baseline (major molecular response [MMR] international scale [IS]: 0.1%).
Several studies have shown that a further reduction of residual leukemic cells of 4.0 logs or 
more (i.e. achieving a complete molecular response [MR4.0 or better, i.e. ≥MR4.0] compared to 
an MMR) is associated with the most favorable outcome for patients in CML-CP. In a study 
of 90 patients with a CCyR, only one out of 28 patients with a ≥MR4.0 subsequently lost their 
CCyR, whereas 11 out of 48 with an MMR subsequently lost their CCyR (Press 2007). In a 
study by Kantarjian (2008) of 276 patients treated with imatinib, 100 patients achieved a 
≥MR4.0, with no treatment failures (classified as sustained ≥MR4.0 for 6 months or more). A 
third study published by Branford (2008) demonstrated in a series of 144 patients treated with 
imatinib who achieved an MMR, that the lowest frequency of recurrence occurred in the 
55 patients with a ≥MR4.0 (1.8%) compared with 89 patients with an MMR but not a ≥MR4.0
(7.9%). These studies support the goal of therapy for newly diagnosed CML-CP as being 
attainment of ≥MR4.0, as this is associated with the most favorable outcome.
The gold standard for the treatment of CML was the tyrosine kinase inhibitor (TKI) Glivec®
(imatinib). Nilotinib (Tasigna®, AMN107) is a second-generation TKI with improved target 
specificity over imatinib. Its efficacy and safety in the treatment of patients who are 
resistant/intolerant to imatinib (Kantarjian 2006; Kantarjian 2007; le Coutre 2008) led to its 
registration for the second-line treatment of CML-CP and CML-AP. More recently, nilotinib 
has been approved for the first-line treatment of newly diagnosed CML-CP patients. The 


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5-year follow-up from the pivotal nilotinib study [CAMN107A2303] in this indication 
(Larson 2014) confirmed the superiority of nilotinib 300 mg twice daily (BID) or 400 mg BID 
over imatinib 400 mg once daily (QD) in terms of the MMR rates (77%, 77%, and 60%, 
respectively) and in achieving MR4.5 (54%, 52%, and 31%) by 5 years. In particular, the 
estimated rate of progression to AP/BC was also significantly lower in both nilotinib 
treatment arms (0.7%, 1.1%) than in the imatinib treatment arm (4.2%).
The National Comprehensive Cancer Network guidelines on CML (version 2, 2012) and the 
European Leukemia Net guidelines (Baccarani et al 2013) recommend continuing TKI 
treatment (i.e. imatinib or nilotinib) indefinitely in all responding patients. There are currently 
no recommendations or provisions for temporary or permanent treatment-free remission (TFR) 
phases with any TKI.
1.2
Introduction to investigational treatment(s) and other study 
treatment(s)
1.2.1
Overview of nilotinib
Nilotinib (Tasigna®, AMN107) is a rationally designed second-generation TKI with improved 
target specificity over imatinib. Tasigna® is approved for the treatment of adult patients with 
Ph+ CML-CP or -AP resistant to or intolerant to at least one prior therapy, including imatinib, 
and also for the treatment of adult patients with newly diagnosed Ph+ CML-CP. Efficacy data 
in patients with CML-BC are not available.
Nilotinib is an adenosine triphosphate-competitive inhibitor of the tyrosine kinase activity of 
the native ABL as well as the chimeric fusion protein BCR-ABL and thereby prevents the 
activation 
of 
BCR-ABL-dependent 
mitogenic 
and 
anti-apoptotic 
pathways 
(e.g. 
phosphatidylinositol-3kinase [PI-3K] and signal transducer and activator of transcription 
[STAT5]), leading to the death of the BCR-ABL phenotype in CML (Manley 2010). As well 
as being a highly potent and selective inhibitor of BCR-ABL, nilotinib also maintains activity 
against many imatinib-resistant mutant forms of BCR-ABL (Weisberg 2005). In murine 
models of CML, sole treatment with oral nilotinib reduces tumor burden and prolongs 
survival. In primary Ph+ leukemia cell lines from CML patients, nilotinib selectively inhibits 
proliferation and induces apoptosis. Nilotinib has little or no effect against the majority of 
other protein kinases examined, including Src, except for the platelet-derived growth factor, 
Kit, and ephrin receptor kinases, which it inhibits at concentrations within the range achieved 
following oral administration at therapeutic doses recommended for the treatment of CML.
1.2.1.1
Non-clinical experience
Data from preclinical studies demonstrate that nilotinib achieves higher intracellular 
concentrations than imatinib, and that nilotinib inhibits BCR-ABL tyrosine kinase activity and 
induces apoptosis at lower concentrations than imatinib (le Coutre et al 2004; White et al 
2006). Therefore, based on the preclinical data, and observed efficacy of nilotinib in imatinib-
resistant and -intolerant patients, nilotinib was predicted to have significant efficacy in newly 
diagnosed CML-CP patients.


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In a mouse study, skin growth or skin cancer were detected at doses representing
approximately 30 to 40 times the human exposure at the maximum approved dose. At doses
that were approximately 10 to 20 times the human exposure at the maximum approved dose,
no observed overgrowth of the skin was detected. In this study the major non-cancer lesions
were in the skin, the growing teeth (degeneration/atrophy of the enamel and inflammation of
the gingiva) and the thymus (low lymphocytes). There are currently no clinical data
suggesting an increased risk of skin cancer in patients treated with Tasigna.
For more details on non-clinical experience, please refer to the latest [AMN107 Investigator 
Brochure].
1.2.1.2
Clinical experience
1.2.1.2.1 Clinical safety and tolerability
Overall, nilotinib has been found to be well tolerated in patients with Ph+ CML-CP, and -AP 
who were resistant to or intolerant of imatinib, as well as in patients with newly diagnosed 
Ph+ CML-CP.
While adverse events (AEs) are common in patients with CML treated with nilotinib, they are 
generally mild to moderate, reversible, and manageable with dose interruption and/or dose 
reduction. The most common grade 3 or 4 toxicities are hematologic, which are not 
unexpected in the CML population and are generally manageable. Hematotoxicity is more 
frequent in patients with imatinib-resistant or -intolerant CML and in particular in patients 
with CML-AP and CML-BC. The most commonly reported non-hematologic adverse 
reactions in patients with newly diagnosed Ph+ CML-CP, resistant or intolerant Ph+ CML-CP, 
or resistant or intolerant Ph+ CML-AP are rash, pruritus, headache, nausea, fatigue, myalgia, 
nasopharyngitis, constipation, diarrhea, abdominal pain, vomiting, arthralgia, pyrexia, upper 
urinary tract infection, back pain, cough, and asthenia. Hematologic adverse drug reactions 
include myelosuppression: thrombocytopenia, neutropenia, and anemia. In comparison to 
first-line patients, grade 3/4 AEs were more frequently observed in CML patients resistant to 
or intolerant of prior therapy, including imatinib. Other significant drug effects reported with 
nilotinib include modest QTc prolongation, elevations of blood glucose, bilirubin, lipase, and 
transaminases, which are manageable with dose interruptions and reductions.
No major differences in safety or efficacy have been observed in patients ≥65 years of age. 
Clinical studies have not been performed in patients with impaired renal function.
For detailed information regarding nilotinib clinical safety and tolerability, please refer to the 
latest [AMN107 Investigator Brochure].
Ischemic Vascular and Ischemic Cardiovascular Events Reported for 
CAMN107A2303 (ENESTnd Study)
Newly diagnosed or worsened ischemic vascular and ischemic cardiovascular events, such as 
ischemic heart disease (IHD), ischemic cerebrovascular events (ICVE) or peripheral artery 
occlusive disease (PAOD) have occurred in a relatively small number of CML-CP patients 
while on study medication. However, such events have been reported with higher frequency 
in the nilotinib treatment arms compared with the imatinib treatment arm. Up to the data cut-


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off for the 60-month analysis (30-Sep-2013), the number of patients reported with events is as 
follows:

Nilotinib 300 mg BID: IHD, 11 (3.9%); ICVE, 4 (1.4%); PAOD, 7 (2.5%)

Nilotinib 400 mg BID: IHD, 24 (8.7%); ICVE, 9 (3.2%); PAOD, 7 (2.5%)

Imatinib 400 mg QD: IHD, 5 (1.8%); ICVE, 1 (0.4%); PAOD, 0 (0.0%)
The majority of reported ischemic vascular and ischemic cardiovascular events were in 
patients with associated risks (e.g. advanced age, hypertension, hyperlipidemia, 
hypercholesterolemia, smoking, diabetes mellitus, pre-existing peripheral vascular disease).
The background incidence of these events has not been established for the CML patient 
population.
1.2.1.2.2 Pharmacokinetics/pharmacodynamics of nilotinib
Approximately 30% of a nilotinib dose is absorbed after oral administration, with peak 
concentrations reached at 3 hours after dosing. Plasma protein binding is high (approximately 
98%) and independent of dose.
Nilotinib is metabolized in the liver via oxidation and hydroxylation pathways, mediated 
primarily by CYP3A4. Nilotinib was identified as the main circulating component in the 
serum, while none of the metabolites was found to contribute significantly to the 
pharmacological activity of nilotinib. In humans, excretion of nilotinib occurred exclusively 
through the fecal route, with no renal elimination of the drug or its metabolites observed. The 
average elimination half-life (t1/2) of nilotinib is 17 hours.
With multiple oral doses of nilotinib, steady-state conditions were achieved by Day 8 after 
starting treatment. There were 2-fold and 3.8-fold accumulations with QD and BID dosing, 
respectively. Inter-patient variability (coefficient of variation [CV%]) in nilotinib 
pharmacokinetics (PK) was moderate to high, with CV% being 32% to 64% in area under the 
serum concentration-time curve (AUC) and 34% to 72% in maximum plasma concentration 
(Cmax), respectively.
The bioavailability of nilotinib is increased by food: healthy volunteer studies showed 
increases in Cmax and AUC of up to 112% and 82%, respectively (30 hours after high-fat meal, 
versus fasting conditions). Concurrent intake of grapefruit juice increased the nilotinib Cmax
and AUC0-∞, but the median time to reach peak concentration and the mean t1/2 were not 
altered.
With QD dosing of nilotinib from 50 to 1200 mg at steady state, Cmax and AUC increased 
with increasing dose from 50 to 400 mg in a generally dose-proportional manner, but 
appeared to plateau at dose levels above 400 mg. Dividing the daily dose into a BID schedule 
partially overcame the dose-limiting absorption; exposure to nilotinib with 400 mg BID was 
approximately 35% greater than with 800 mg QD.
Systemic exposure (AUC) of nilotinib at steady state at a dose level of 400 mg BID was 
approximately 13.4% higher than at a dose level of 300 mg BID. The average nilotinib Cmax
and minimum plasma concentration (Cmin) over 12 months were approximately 15.7% and 
14.8% higher, respectively, following 400 mg BID dosing compared to 300 mg BID, 
suggesting a less than proportional dose-exposure relationship between nilotinib 300 mg BID 


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and 400 mg BID. Bioavailability and systemic exposure may be lower in male patients;
studies have shown 10% to 20% lower systemic exposure in males versus females.
Hepatic impairment has a modest effect on nilotinib PK, increasing AUC0-∞by 35%, 35%, 
and 19% in patients with mild, moderate, and severe hepatic impairment, respectively, versus 
patients with normal hepatic function. Impaired renal function is not expected to influence 
nilotinib PK. Nilotinib absorption (relative bioavailability) may be reduced by approximately 
48% and 22% in patients with total gastrectomy and partial gastrectomy, respectively.
The administration of nilotinib with agents that are strong cytochrome P450 (CYP)3A4 
inhibitors (including, but not limited to ketoconazole, itraconazole, voriconazole, 
clarithromycin, telithromycin, and ritonavir) should be avoided. Concomitant use of nilotinib 
with medicinal products that are potent inducers of CYP3A4 (e.g. phenytoin, rifampicin, 
carbamazepine, phenobarbital, and St. John’s wort) is likely to reduce exposure to nilotinib to 
a clinically relevant extent. For further information, see the [AMN107 Investigator Brochure].
1.2.1.2.3 Efficacy of nilotinib
Overall, approximately 11,764 patients have been exposed to nilotinib in clinical trials as of 
31 January 2015.
Nilotinib is approved by US Food and Drug Administration (FDA) and European 
Commission to treat newly diagnosed adult patients with Ph+ CML-CP, and to treat Ph+ 
CML-CP and CML-AP in adult patients resistant to or intolerant of prior therapy, including 
imatinib. The recommended adult dosage of nilotinib is 300 mg orally BID for newly 
diagnosed Ph+ CML-CP patients and 400 mg orally BID for patients with resistant or 
intolerant Ph+ CML-CP or CML-AP.
The results of study ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–
Newly Diagnosed Patients) demonstrated superiority of nilotinib versus imatinib in the CML-
CP first-line setting (Saglio et al 2010; Larson et al 2012). More patients treated with nilotinib 
achieved deeper molecular responses, and the differences were significantly superior at each 
of the analyzed time points to date. The rate of MMR at 12 months was 44% in the nilotinib 
300 mg BID treatment arm and 22% in the imatinib treatment arm p<0.001 (primary 
endpoint). The cumulative incidence of MR4.5 log reduction from standardized baseline was 
11%, 25%, and 32% by 12, 24, and 36 months in the nilotinib 300 mg BID arm. In the 
imatinib arm, the rates were 1%, 9%, and 15% at the same time points. The differences 
between the rates of MR4.5 in the nilotinib and imatinib arms increased over time.
For additional details human studies in CML, see the [AMN107 Investigator Brochure].


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2
Rationale
2.1
Study rationale and purpose
The natural history of CML was changed dramatically by the introduction of TKIs, which 
have increased patient survival and consequently have prolonged the duration and increased 
the prevalence of the disease. It is estimated that the number of CML cases will continue to 
increase over the next half century, with the number of patients expected to exceed 250,000 in 
the USA alone.
The TKI imatinib has been the gold standard in the treatment of Ph+, BCR-ABL+ CML for 
more than 10 years, with approximate cumulative responses of 70% of patients achieving a 
CCyR and 50% achieving a 3-log reduction in BCR-ABL IS or an MMR following treatment 
(Clark et al 2012). Studies have demonstrated that the survival of imatinib-treated patients is 
similar to that of non-CML patients; however, the proportion of patients who achieve a stable 
molecular response of below 4-log or more (i.e. MR4.0, MR4.5, and MR5.0) is much smaller, 
and ranges between 26% for MR4.0 and 15% for MR4.5 after 3 years of follow-up (Clark et al 
2012).
Several results from independent study groups have proven that discontinuation of patients 
from imatinib treatment is possible, with the risk of relapse being between 40% and 60% and 
occurring most frequently within the first year of discontinuation (Mahon et al 2010). As a 
prerequisite for any discontinuation attempt however, patients must have achieved a sustained 
deep molecular response for an extended duration of time. The depth of molecular remission 
is not consistent among the trials conducted; however, it is felt that a sustained molecular 
remission of ≥MR4.0 will provide adequate protection from relapse after cessation of treatment 
for at least a notable proportion of the population. (Cross et al 2012)
Studies have demonstrated that patients who achieve a low level of BCR-ABL can 
subsequently show fluctuations of their molecular responses due to individual patient biology. 
Indeed, data from the ENESTnd study ([CAMN107A2303]), a pivotal phase III study of 
nilotinib versus imatinib in first-line treatment; Novartis, Larson, R, et al. Blood. 2014 
[abstract 4541] suggest that approximately 30% of patients will have fluctuations in 
BCR-ABL above the given threshold of a 4.5-log reduction in BCR-ABL. Therefore a 
sustained molecular remission of ≥MR4.0 serves to reduce the number of patients eligible for 
treatment cessation further.
From the considerations above, it is recognized that only a small proportion of 
imatinib-treated patients are eligible for an attempt at treatment cessation; and data have 
shown that almost 50% of patients undergo a molecular relapse upon treatment interruption. 
For patients not achieving a deep molecular response on imatinib treatment after 2 years, the 
chances of doing so at a later date is very small, and therefore the chances of participating in a 
cessation attempt is further reduced.
Nilotinib is an imatinib derivative that has a greater activity on the kinase activity of 
BCR-ABL, either wild type or with most mutations associated with imatinib resistance
(Weisberg et al 2005), that has been proven to induce a CCyR in about 50% of the patients 
who were resistant to imatinib treatment (Kantarjian et al 2006). Subsequently, it was 


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demonstrated that nilotinib induced CCyR and MMR to a greater extent than imatinib in 
first-line treatment (Saglio et al 2010). Nilotinib is registered for the second-line treatment of 
CML at a dose of 400 mg BID and for the first-line treatment of CML at a dose of 300 mg 
BID. The data from the ENESTnd study showed that the molecular response to nilotinib is not 
only higher and faster, but also deeper, with an MR4.0 rate of approximately 30% by 2 years 
and 50% by 3 years (Clark et al 2012).
In addition, data from the ongoing Evaluating Nilotinib Efficacy and Safety in Clinical Trials-
Complete Molecular Response (ENESTcmr) study shows that patients with a lack of deep 
molecular response on imatinib can benefit from treatment with nilotinib by reaching deeper 
levels of molecular response compared to continuation of treatment with imatinib (Cervantes 
et al 2012). In this study the primary endpoint, defined as undetectable BCR-ABL in two 
consecutive samples was not reached; however, twice as many patients who switched to 
nilotinib achieved MR4.5 versus patients who continued on imatinib. Overall, 9% of patients 
who were switched to nilotinib discontinued the study prematurely due to AEs, in comparison 
to 1% of patients who continued on imatinib.
In the context of the increasing prevalence of CML, TFR studies may serve to both provide a 
new treatment paradigm for patients (with respect to the minimization of drug-drug 
interactions, elimination of chronic side effects, and benefit of pregnancy without exposure to 
TKIs), but may also have a positive impact on health economics considering the expected 
increase in the numbers of patients with the disease.
CML-CP patients who have received 24 or more months of imatinib treatment and have failed 
to achieve the MR threshold for treatment cessation have a 50% greater chance of achieving
this level of MR by switching to nilotinib; however, the optimal duration of consolidation 
treatment with nilotinib to ensure the highest rate of patients remaining in ≥MR4.0 after 
suspending treatment is not yet known. Several attempts were made to assess the impact of 
the duration of sustained molecular remission (e.g. Mahon et al 2010, Ross et al 2010) with
inconclusive results. Therefore within the current protocol, it is planned to assess this duration 
as an integral part of the study design, randomizing the patients to either a 12-month or a 24-
month consolidation phase before treatment cessation and assessing the potential impact of a 
longer duration of consolidation treatment with nilotinib on molecular relapse rate in the first 
12 months of the TFR phase.
2.2
Rationale for the study design
This is an open-label, multicenter, randomized, two-arm study aiming to identify the duration 
of nilotinib treatment that enables a highest percentage of patients to remain in TFR (≥MR4.0) 
12 months after starting the TFR phase of the study.
In a previous study (ENESTcmr), MR4.5 was achieved after 24 months of treatment with 
nilotinib in 43% of CML-CP patients lacking a deep MR after having been on imatinib for at 
least 2 years. For this reason, it is expected that 24 and 36 months of treatment with nilotinib 
300 mg BID may induce greater percentages of patients to achieve sustained ≥MR4.0.
The primary efficacy parameter of the number of patients remaining in TFR (≥MR4.0) will be 
determined 12 months after starting the TFR phase in both randomized treatment arms. An 
additional analysis at 24 months will also be performed. Updated results from the STIM study 


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were reported (Mahon et al 2011), which demonstrated that 39 out of 100 off-treatment 
patients remained without detectable BCR-ABL transcript levels after a median 34 months of 
follow-up. Of the 61 patients who had molecular relapses, 58 (95%) relapsed in the first 
7 months of the study, and three molecular recurrences occurred at later time points (months 
19, 20, and 22). This observation is in line with the molecular recurrence patterns described 
by both Mahon et al (2010) and Branford et al (2012). It is therefore anticipated that even if 
patients have a 1- to 2-log lower residual leukemic disease burden at the time of starting the 
TFR phase (as opposed to patients treated with imatinib in previous studies), those who 
experience molecular recurrence during this phase will do so within the same time frame as 
observed in previous discontinuation studies. Assessments of relapse rate at 12 and 24 months 
in the TFR follow-up period are therefore deemed to be sufficient to detect any clinically 
significant difference between the two randomized arms.
Patients who are eligible to enter the TFR phase will be monitored every 4 weeks during the
first 6 months of the phase, with assessments occurring less frequently in the following 18 
months. Studies have shown that in case of molecular recurrence, the increase is on average 1
log per month (Brandford et al 2012; Mahon et al 2010). The monthly monitoring during the
first 6 months of the TRF phase (when most recurrences are anticipated) will therefore ensure 
that impending recurrence is identified early enough to avoid loss of CCyR by timely 
re-initiation of nilotinib treatment.
It is also hypothesized, primarily from the STIM study, that virtually all patients with 
molecular recurrence after the TFR phase will regain MMR, as well as ≥MR4.0, within 
approximately 3 months of re-initiating treatment. Therefore, patients with molecular 
recurrence during the TFR phase will be re-treated immediately with nilotinib 300 mg BID 
and will remain on study until they complete the 5-year study period.
No formal interim analyses are planned during the study; however, as this study will be 
overseen by a Data Monitoring Committee (DMC), DMC reports will be provided on a 
regular basis (see Section 8.6).
2.3
Rationale for dose and regimen selection
In the first 12 months following the switch from imatinib to nilotinib 400 mg BID treatment in 
the ENESTcmr study, 9% of patients discontinued due to AEs. It is therefore suggested that 
administration of the currently marketed nilotinib 300 mg BID dose will result in similar 
efficacy and fewer discontinuations in the current trial due to AEs. Additionally, 
administration of nilotinib 300 mg BID appears justified, as CML-CP patients on imatinib 
who have achieved CCyR but less than MR4.0 are not considered to be treatment failure 
patients according to current treatment recommendations. The selection of the 300 mg BID 
dose is therefore considered appropriate in order to minimize the occurrence of AEs when 
moving from imatinib to nilotinib, and to provide the best long-term efficacy.
2.4
Rationale for choice of combination drugs
Not applicable.


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2.5
Rationale for choice of comparators drug
Not applicable.
2.6
Rationale for optional Stem cells ENESTPath substudy
“Leukemic stem cells quantification in patients with chronic myelogenous leukemia included 
in the ENESTPath trial”:
In two randomized studies ([CAMN107A2303] and [CAMN107A2405]), nilotinib has been 
shown to be significantly more effective than imatinib in inducing deep MR in CML-CP
patients. In ENESTnd [CAMN107A2303], nilotinib allowed a higher number of newly
diagnosed patients to achieve deeper MR (MR4.0 or MR4.5) compared to imatinib. In 
ENESTcmr [CAMN107A2405] in CML-CP patients after prolonged treatment with imatinib, 
twice as many patients in the nilotinib arm than in the imatinib arm achieved MR4.5 after 
12 months of treatment. It is then possible that a deeper MR is a marker for a decreased 
number or eradication of leukemic stem cells (LSC), and that subsequent relapse after 
treatment discontinuation may be correlated with the presence and/or the number of persisting 
LSC.
Taking this hypothesis into account, the focus of this substudy is to evaluate the importance of 
LSC (CD34+/CD38+ progenitor cells, CD34+/CD38−stem cells and CD34+/CD56+ aberrant 
stem cells [the last ones only if detectable]) in the long-term maintenance of the disease and 
their role in the relapse of patients in the TFR phase. This substudy is based on the possibility 
of detection and quantification of LSC and their progenitors by flow cytometry, and also the 
possible differential effect of nilotinib compared to imatinib in these cell populations (Defina 
et al 2012, Janssen et al 2012, Corbin et al 2011).
The hypothesis will be tested by:
1. Evaluating the presence and number of LSC and their progenitors in the bone marrow of 
all patients participating in this substudy before and after completing induction and the 
first year of the consolidation phase (at Visit 8).
2. Evaluating, by descriptive statistics, whether prolonging the treatment period of 
consolidation with nilotinib (patients in Arm 2) causes a reduction in the percentage of 
patients presenting LSC and progenitor cells in bone marrow at the end of the second year 
of the consolidation phase.
3. Performing an exploratory analysis in order to evaluate whether relapse in patients during 
the TFR phase in either arm correlates with the presence of LSC and progenitor cells in 
bone marrow at the end of the consolidation phase and at the time of relapse during TFR.
2.7
Rationale for ‘CML patient’s voice’ Italian Substudy
The ‘CML patient’s voice’ Italian substudy aims to examine patients’ psycho-emotional 
characteristics, quality of life and experiences of being involved in CAMN107AIC05l trial 
and its discontinuation using the following mixed method design (qualitative-quantitative). 
This sub-study will be conducted in Italy only. [Post-text Supplement 1].


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3
Objectives and endpoints
Objectives and related endpoints are described in Table 3-1 below.


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Table 3-1
Objectives and related endpoints
Objective
Endpoint
Analysis
Primary
Refer to Section 10.4.
To assess the optimal duration of consolidation 
treatment with nilotinib 300 mg BID in order that 
patients remain in TFR (≥MR4 0) without molecular 
relapse 12 months after entering the TFR phase.
The number of patients who remain in TFR (≥MR4.0) 
without molecular relapse at the end of 12 months in 
the TFR phase of the study, in the nilotinib 12-month 
consolidation treatment arm versus the nilotinib 24-
month consolidation treatment arm. Molecular relapse 
during TFR is defined as the loss of MMR, or the 
confirmed loss of MR4.0 (defined by 3 consecutive 
tests less than MR4.0 assessed at 3 consecutive visits 
according to the visit schedule of the TFR phase) (see 
Section 4.1).
The proportion of patients who are in TFR (≥MR4 0) 
without molecular relapse at the end of 12 months in 
the TFR phase will be calculated by dividing the 
number of patients who remain in ≥MR4.0 at the end of 
12 months in the TFR phase (without re-starting 
nilotinib therapy) by the number of patients who 
entered the TFR phase. A chi-square test will be 
applied to compare the two treatment arms.
Secondary
Refer to Section 10.5.
To evaluate the proportion of patients who are eligible 
to suspend nilotinib therapy by achieving and 
maintaining a sustained ≥MR4.0 for at least 12 months 
during consolidation treatment with nilotinib 300 mg 
BID.
The proportion of patients who achieve a sustained 
≥MR4.0 (defined as having 4 out of 5 quarterly 
assessments of ≥MR4.0 by a (EUTOS) standardized 
laboratory over the last 12 months and the last 
assessment before randomization is at least MR4 0) 
during the consolidation phase of the study.
The proportion of patients who are in sustained ≥MR4 0
at 24 months after completing the 
induction/consolidation phase will be calculated by 
dividing the number of patients who have achieved 
sustained ≥MR4 0 over at least the last 12 months of 
the consolidation phase by the number of patients 
enrolled.


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Objective
Endpoint
Analysis
To assess the achievement of MMR, MR4 0, and MR4 5 
during induction/consolidation treatment with nilotinib 
300 mg BID at the different time points in patients 
without that response at study entry.
To assess the molecular response in patients during 
induction/consolidation treatment with nilotinib 300 mg 
BID at the different time points.
The proportion of patients who achieve MMR, MR4 0,
or MR4.5 on the study at selected time points (every 3 
months until Month 24 or Month 36 depending on the 
randomized arm) during the induction/consolidation 
phase of the study.
The proportion of patients who are in MMR, MR4.0, or 
MR4.5 on the study at selected timepoints (every 3 
months until Month 24 or Month 36 depending of the 
randomized arm) during the induction/consolidation 
phase of the study.
The proportion of patients who achieve MMR, MR4 0 or 
MR4 5 at selected timepoints during the 
induction/consolidation phase (every 3 months until 
Month 24 or Month 36 depending on the randomized 
arm) will be calculated by dividing the number of 
patients who are in MMR, MR4.0 or MR4 5 by the 
number of patients without that response at baseline.
The proportion of patients who are in MMR, MR4.0, or 
MR4 5 at selected timepoints during the TFR phase 
(every 3 months until Month 24 or Month 36 
depending on the randomized arm) will be calculated 
by dividing the number of patients who are in MMR, 
MR4 0, or MR4 5 by the number of enrolled patients.
To assess the proportion of patients in TFR at 3, 6, 12, 
18 and 24 months after nilotinib cessation in the two 
treatment arms
The proportion of patients in TFR, i.e. with no 
confirmed loss of MR4.0, no loss of MMR and no 
restarting of nilotinib therapy within the first 3, 6, 12, 
18, and 24 months following nilotinib cessation. 
The proportion of patients in TFR will be calculated by 
dividing the number of patients with no confirmed loss 
of MR4 0, no loss of MMR, and no re-starting of nilotinib 
therapy in the first 3, 6, 12, 18, and 24 months 
following nilotinib cessation by the number of patients 
who entered the TFR phase
To assess the molecular response in patients after 
randomization in the two treatment arms.
The proportion of patients who are in MMR, MR4.0, or 
MR4.5 at selected time points (at Month 3, 6, 12, and
every 3 months thereafter until Month 24 or Month 36 
depending on the randomized arm) during the TFR 
phase in each one of the two treatment arms.
The proportion of patients who are in MMR, MR4.0, or 
MR4 5 at selected time points (at Month 3, 6, 12, and 
every 3 months thereafter until Month 24 or Month 36 
depending on the randomized arm) will be calculated 
by dividing the number of patients who are in MMR, 
MR4 0 or MR4.5 by the number of patients in the TFR 
phase in each one of the two treatment arms.
To assess the kinetics of BCR-ABL transcript during 
induction/consolidation treatment with nilotinib 300 mg 
BID
BCR-ABL transcript levels (IS) during the 
induction/consolidation phase
Descriptive statistics of BCR-ABL transcript levels (IS) 
over time during the induction/consolidation phase
To assess the kinetics of BCR-ABL transcript during 
the TFR phase in the two treatment arms
BCR-ABL transcript levels (IS) during the TFR phase
Descriptive statistics of BCR-ABL transcript levels (IS) 
over time during the TFR phase


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Objective
Endpoint
Analysis
To assess the kinetics of BCR-ABL transcript during 
the nilotinib re-treatment phase
BCR-ABL transcript levels (IS) during the nilotinib re-
treatment phase
Descriptive statistics of BCR-ABL transcript levels (IS) 
over time during the nilotinib re-treatment phase
To assess the progression-free survival (PFS) rate 
after randomization in the two treatment arms.
PFS is defined as progression to AP/BC or death from 
any cause, where the “failure” event is the earliest 
occurrence of either of these events.
Kaplan-Meier (KM) estimation of PFS. PFS is 
measured from the date of randomization to the date 
of the earliest failure event. Patients not known to 
have progressed or died on or before the cut-off date 
for the KM analysis will have their PFS censored at the 
earlier of the date of their last assessment 
(cytogenetic, hematology, or extramedullary) for 
patients who are still on study and at the date of last 
contact for patients who are in follow-up.
To assess treatment-free survival (TFS) after start of 
the TFR phase in the two treatment arms.
TFS is defined as lack of any of the following events: 
loss of MMR, confirmed loss of MR4.0, re-start of 
nilotinib treatment for any reason, progression to 
AP/BC, or death from any cause.
KM estimation of TFS, which is measured from the 
start of the TFR phase to the date of the earliest of the 
following: loss of MMR, confirmed loss of MR4.0, (see 
Section 4.1) re-start of nilotinib treatment, progression 
to AP/BC, or death from any cause. Patients not 
known to have had any of the events on or before the 
cut-off date for the KM analysis will have their TFS 
censored at the earlier of the date of their last 
assessment (PCR, cytogenetic, hematology, or 
extramedullary) for patients who are still on study and 
the date of last contact for patients who are in 
follow-up.
To assess the overall survival (OS) rate after 
randomization in the two treatment arms.
Overall survival is defined as the time from 
randomization to the time of death due to any cause.
KM estimation of OS, which is measured from the date 
of randomization to the date of death due to any 
cause. For patients not known to have died on or 
before the cut-off date, survival time will be censored 
at the date of last contact.


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Objective
Endpoint
Analysis
To assess the safety profile of nilotinib during the 
induction/consolidation phase, the TFR phase, and 
during the re-treatment phase.
Safety will be monitored through assessment of 
Adverse Events, laboratory data, ECG, vital signs.
Descriptive statistics on AEs, laboratory abnormalities,
and clinically notable ECG and other safety 
parameters during the nilotinib induction/consolidation 
phase, during the TFR phase, and during re-initiation 
of treatment with nilotinib.
For those patients consenting to participate in the 
optional Stem cells ENESTPath substudy, the 
following objectives will be also applicable:
To evaluate the presence and number of LSC and 
their progenitors in the bone marrow of all patients 
participating in this substudy before and after 
completing induction and first year of consolidation 
phase (at Visit 8 ).
To evaluate whether prolonging the treatment period 
of consolidation with nilotinib (patients in Arm 2 versus 
patients in Arm 1) induces a reduction in the 
percentage of patients presenting LSC and progenitor 
cells in bone marrow at the end of the second year of 
the consolidation phase (Visit 204 for Arm 2 versus 
Visit 8 for Arm 1);
To perform an exploratory analysis in order to evaluate 
whether relapse in patients during the TFR phase in 
either arm correlates with the presence of LSC and 
progenitor cells in bone marrow at the end of the 
consolidation phase and at the time of relapse during 
TFR.
The following endpoints are applicable to all the 
objectives detailed for the optional Stem cells 
ENESTPath substudy: 
Proportion of patients with presence of Ph+ LSC in 
bone marrow (CD34+/CD38+ progenitor cells, 
CD34+/CD38−stem cells, and CD34+/CD56+ 
aberrant stem cells [the last ones only if detectable]) at 
screening and at Visit 8.
Proportion of patients with presence of Ph+ LSC in 
bone marrow (CD34+/CD38+ progenitor cells, 
CD34+/CD38−stem cells, and CD34+/CD56+ 
aberrant stem cells [the last ones only if detectable]) at 
the end of consolidation arm (Visit 8 for Arm 1 and 
Visit 204 for Arm 2).
Proportion of patients with or without molecular 
relapse in the first year of TFR in either arm by 
presence of LSC in bone marrow (CD34+/CD38+ 
progenitor cells, CD34+/CD38−stem cells, and 
CD34+/CD56+ aberrant stem cells [the last ones only 
if detectable]) at Visit 8 and at the time of relapse 
during TFR.
The percentage of patients presenting Ph+ LSC in 
bone marrow will be calculated at each time point and 
descriptively analyzed. 
Descriptive statistics.
Descriptive statistics.
For the ‘CML patient’s voice’ Italian substudy please refer to [Post-text Supplement 1]


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4
Study design
4.1
Description of study design
This is a prospective, randomized, open-label, multicenter, two-arm Phase III study aiming to 
assess the optimal duration of nilotinib 300 mg BID consolidation treatment, in order that 
patients remain in TFR (MR4.0 or better [≥MR4.0]) 12 months after entering the TFR phase of 
the study.
The study design includes a 12-month induction phase, followed by a 12- or 24-month 
consolidation phase, and a 24- or 36-month TFR phase depending on randomization
(Figure 4-1).
Figure 4-1
ENESTPath study design
Eligible patients are adults with a confirmed diagnosis of chronic phase Ph+ and/or 
BCR-ABL+ CML who have been treated with first-line imatinib for 24 months or more, and 
are at least in CCyR. Patients must not have achieved ≥MR4.0 at study entry, as assessed by a 
EUTOS standardized laboratory.


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Approximately 565 patients will be enrolled into the study and will be treated with nilotinib 
300 mg BID for 24 months. Following 24 months of treatment, patients in sustained 
molecular response for at least the last 12 months will be randomized on a 1:1 basis to either:

Suspend nilotinib treatment immediately and enter the TFR phase (the nilotinib 24-month 
treatment arm; Arm 1), or

Continue nilotinib treatment for a further 12 months, then suspend treatment and enter the 
TFR phase (the nilotinib 36-month treatment arm; Arm 2).
Patients will be deemed to be in sustained molecular response if:

Four out of the preceding five quarterly real-time quantitative polymerase chain reaction 
(RQ-PCR) assessments were ≥MR4.0, and

The last assessment was ≥MR4.0.
Patients not achieving a sustained molecular response at 24 months from treatment start (and 
subsequently at 36 months from treatment start depending on the randomization arm) will exit 
the study and will be treated at the discretion of the investigator according to standard practice. 
Information on survival, stem cell transplantation, status of the patient’s disease (i.e. disease 
progression to AP/BC according to protocol definition, TKI treatment) will be collected until 
death or until 5 years from study entry, whichever comes first.
Patients relapsing during the TFR phase will enter the nilotinib re-treatment phase of the study 
and will be re-treated with the same dose of nilotinib as they were on before the TFR phase 
(i.e. the re-treatment dose will be nilotinib 300 mg BID or a lower dose of nilotinib if the dose
was reduced in the consolidation phase before entering the TFR phase). The patient will
subsequently remain on study until the completion of the 5-year study period.
Relapse is defined as the loss of MMR, or the confirmed loss of MR4.0 (defined by three
consecutive tests less than MR4.0 assessed at three consecutive visits according to the visit 
schedule of the TFR phase). If during the three consecutive tests, one of the tests shows loss 
of MMR, this patient will be declared as relapsing and will start the nilotinib re-treatment 
phase immediately even if the definition of confirmed loss of MR4.0 is not yet fulfilled.
Loss of MMR is considered a more clinically relevant criterion for re-initiating nilotinib 
treatment than loss of MR4.0 due to the anticipated fluctuations in BCR-ABL transcript levels 
at low levels without systematic rise in patients with minimal residual disease.
4.1.1
Description of optional Stem cells ENESTPath substudy
The Stem cells ENESTPath substudy adds the determination of Ph+ stem cells in bone 
marrow at the following time points, in patients providing separate specific consent to 
participate in the substudy (Figure 4-2):
a) During the screening, before starting nilotinib 300 mg BID treatment
b) After 2 years of nilotinib treatment at Visit 8
c) After 3 years of nilotinib treatment, only in patients with 2 years of consolidation treatment 
(Arm 2) at Visit 204
d) If the patient relapses during the TFR phase, before re-starting the treatment with nilotinib


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A 10-mL bone marrow sample will be obtained and sent to 
 
 for immunophenotype analysis, FACS cell purification, 
fluorescent in situ hybridization (FISH) and RT-PCR. Measurement will be performed by 
flow cytometry in a bone marrow purified population of stem cells in order to detect the 
presence of leukemic Ph+ cells (evaluated by FISH) or BCR-ABL transcripts (evaluated by 
RT-PCR).
Figure 4-2
Optional Stem cells ENESTPath substudy design
4.1.2
Description of ‘CML patient’s voice’ Italian substudy
Italian CAMN107AIC05 patients in consolidation phase consenting to participate will be 
included in the ‘CML patient’s voice’ Italian substudy. See [Post-Text Supplement 1]
4.2
Timing of interim analyses and design adaptations
No formal interim analyses are planned. There will be no publication of results until
enrollment has been completed.
If Novartis decides to publish interim data after enrollment is completed, details will be 
specified in the analysis plan.


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As this study will be overseen by a Data Monitoring Committee (DMC), DMC reports will be 
provided on a regular basis.
Should a predetermined number of patients fulfill the criteria of molecular relapse within the 
TFR phase, the further conduct of the study will be evaluated by the DMC. Any events of 
progression to AP/BC, loss of CCyR, or failure to regain MMR in case of re-initiation of 
treatment for molecular recurrence will be closely monitored by the Novartis Clinical Trial 
Team and the DMC during the entire TFR phase. General stopping rules during the first 
12 months of the TFR phase have been predetermined and are presented in Section 4.4.
4.3
Definition of end of the study
The study will continue until the last patient who was eligible for randomization has 
completed 5 years from study entry, or has been withdrawn from the study. The total maximal 
study duration is therefore 5 years for every patient.
4.4
Early study termination
Predefined stopping rules during the first 12 months of the TFR phase will trigger an 
immediate DMC teleconference. It is the DMC’s responsibility to take the final decision on 
the conduct of this trial.
The stopping rules are based on the frequency of specific events occurring in the ENESTnd 
study [CAMN107A2303]. It is considered crucial that patients treated on this study have 
outcomes during the TFR phase that are comparable or better than those of patients who were 
treated with continuous nilotinib therapy (300 mg BID or 400 mg BID) in the ENESTnd study 
[CAMN107A2303].
Therefore, the following stopping rules for this study will apply to the first 12 months of the 
TFR phase:
1. More than 2 cases of progression to AP/BC, or
2. More than 2 cases of loss of CCyR without re-achievement of CCyR within 6 months of 
nilotinib re-treatment, or
3. More than 9 cases of loss of MMR without re-achievement of MMR within 3 months of 
nilotinib re-treatment
and despite full compliance with BCR-ABL monitoring during the TFR phase for all three 
groups described above and despite full compliance with nilotinib treatment during the 
nilotinib re-treatment phase for groups 2 and 3 (patients with loss of CCyR and patients with 
loss of MMR) according to protocol.
Novartis can terminate the study at any time for appropriate reasons. Should this be necessary, 
the patient should be seen as soon as possible, and the same assessments should be performed 
as described in Section 7.1.8 for a prematurely withdrawn patient. The investigator may be 
informed of additional procedures to be followed in order to ensure that adequate 
consideration is given to the protection of the patient’s interests. The investigator will be 
responsible for informing IRBs and/or IECs of the early termination of the trial.


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5
Population
5.1
Patient population
The study population will consist of adult patients (male or female, aged ≥18 years) with a 
confirmed diagnosis of chronic phase Ph+ and/or BCR-ABL+ CML who have been treated 
first-line with imatinib for 24 months or more, and are at least in CCyR. Patients who have 
previously discontinued imatinib could be enrolled in the trial provided that they have been 
treated with imatinib for 24 months (even not continuously) in total and are in imatinib 
treatment at the time of enrollment. Patients must not have achieved ≥MR4.0 at study entry, as 
confirmed by a EUTOS standardized laboratory with validated PCR technology.
The investigator or designee must ensure that only patients who meet all of the following 
inclusion and none of the exclusion criteria are offered enrollment into the study. Written 
informed consent must be obtained prior to any screening procedures. All data for the 
inclusion/exclusion criteria must be verifiable in the patient’s source documents.
Patients enrolled into this study are not permitted to participate in additional parallel 
investigational drug or device studies.
Optional Stem cells ENESTPath substudy
The study population in the Stem cells ENESTPath substudy will consist of those patients 
participating in the ENESTPath trial who consent to participate in this substudy and who sign 
separate specific informed consent for the stem cells substudy.
There is no cap on patient accrual in each single center; accrual is competitive and will 
continue until the target patient number based on statistical sample size calculation is 
achieved.
‘CML patient’s voice’ Italian substudy
Italian CAMN107AIC05 patients in consolidation phase consenting to participate will be 
included in this substudy. [Post-text Supplement 1]
5.2
Inclusion criteria
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Male or female patients, aged ≥ 18 years
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
3. Documented confirmed diagnosis of chronic phase Ph+ and/or BCR-ABL+ CML-CP. 
Documented chronic phase CML must meet all of the following criteria:

< 15% blasts in peripheral blood and bone marrow

< 30% blasts plus promyelocytes in peripheral blood and bone marrow

< 20% basophils in the peripheral blood

≥100 x 109/L (≥ 100,000/mm3) platelets

No evidence of extramedullary leukemic involvement, with the exception of hepato-
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4. Previous first-line treatment with imatinib for a minimum of 24 months (even not 
continuously) in total and in imatinib treatment at time of enrollment
5. Patient in CCyR (A patient with MMR is considered to be in CCyR. Therefore,
cytogenetic response [CgR] assessment has to be done if a patient has less than MMR in 
the local laboratory result and/or in the blood sample that was sent to the EUTOS 
standardized laboratory at the screening visit [patient will be considered screening failure 
if not in CCyR] see Section 7.1.2 for details);
6. Adequate end-organ function as defined by:

Total bilirubin < 1.5 x upper limit of normal (ULN). Does not apply to patients with 
isolated hyperbilirubinemia (e.g. Gilbert’s disease) grade < 3

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN

Serum lipase ≤2 x ULN

Alkaline phosphatase ≤2.5 x ULN

Serum creatinine < 1.5 x ULN
7. Patients must have the following electrolyte values within normal limits at screening
analysis, or corrected to within normal limits with supplements prior to the first dose of 
study medication:

Potassium

Magnesium

Total calcium
8. Patients must have normal marrow function as defined below:

Absolute Neutrophil Count (ANC) ≥1.5 x 109/L

With the exception of people of North African descent for whom the threshold 
for ANC will be ≥1.0 x 109/L due to an increase in the marginal pool of 
neutrophils

Hemoglobin ≥9.0 g/dL

Platelets ≥100 x 109/L
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests,
and other study procedures;
10. Written informed consent must be obtained prior to any screening procedures.
For those patients consenting to participate in the optional Stem cells ENESTPath substudy or 
in the ‘CML patient’s voice’ Italian substudy, the same inclusion criteria for the ENESTPath 
study will be applicable, plus the following:

Separate specific written informed consent for the Stem cells ENESTPath substudy or 
for the ‘CML patient’s voice’ Italian substudy must be obtained before starting any 
sub-study related assessment like but not limited to extraction of additional bone 
marrow samples for stem cells sub-study.


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5.3
Exclusion criteria
Patients eligible for this study must not meet any of the following criteria:
1.
Achievement of ≥MR4.0 at study entry as assessed by a EUTOS standardized laboratory
2.
Previous treatment with BCR-ABL inhibitors other than imatinib
3.
Patients with detectable atypical BCR-ABL transcripts, defined as absence of typical
BCR-ABL transcripts for CML of the types b2(e13)-a2 or b3(e14)-a2 or both 
simultaneously documented at CML diagnosis or at any time before the screening 
procedure
4.
Previous anticancer agents for CML except for:

Imatinib, and/or

Cytoreduction after CML diagnosis, and/or

Interferon for less than 1 year
5.
Known second chronic phase of CML after previous progression to AP/BC
6.
Known impaired cardiac function, including any of the following:

Inability to determine the QT interval on ECG

Complete left bundle branch block

Right bundle branch block plus left anterior or posterior hemiblock

Use of a ventricular-paced pacemaker

Congenital long QT syndrome or a known family history of long QT syndrome

History of or presence of clinically significant ventricular or atrial tachyarrhythmias

Clinically significant resting bradycardia (< 50 beats per minute)

QTc > 450 msec confirmed on the average of three serial baseline ECGs (using the 
QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, 
electrolytes should be corrected and the patient re-tested for the QTc

History of clinically documented severe peripheral occlusive disease or severe 
ischemic cardiovascular disease (e.g. myocardial infarction, ischemic cerebral 
vascular disease) whenever in the opinion of the investigator other treatments could 
have a more favorable benefit/risk profile.

Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled 
hypertension)
7.
Severe and/or uncontrolled concurrent medical disease that in the opinion of the 
investigator could cause unacceptable safety risks or compromise compliance with the 
protocol (e.g. uncontrolled diabetes, active or uncontrolled infection, uncontrolled severe 
hypertension, or uncontrolled severe dyslipidemia). If appropriate measures (e.g. diet, 
exercise, appropriate therapy) are taken to control blood glucose or cholesterol (LDL)
levels or hypertension, the patient can be re-screened for the study
8.
History of acute pancreatitis within 12 months of study entry, or a past medical history of 
chronic pancreatitis
9.
Known presence of significant congenital or acquired bleeding disorder unrelated to 
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10. History of other active malignancy within 5 years prior to study entry with the exception 
of previous or concomitant basal cell skin cancer, or previous cervical carcinoma in situ 
treated curatively;
11. Patients who have not recovered from prior surgery
12. Treatment with other investigational agents within 30 days of Day 1
13. Patients actively receiving therapy with strong CYP3A4 inhibitors (see link for complete 
list of these medications: medicine.iupui.edu/flockhart/table.htm or Appendix 14.1) 
and/or inducers or medications that have the potential to prolong the QT interval (see
http://crediblemeds.org/everyone/composite-list-all-qtdrugs/?rf=All) that cannot be either 
discontinued or switched to a different medication prior to starting study drug
14. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the 
absorption of study drug
15. Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a 
negative pregnancy test prior to baseline and (d) female of childbearing potential 
unwilling to use contraceptive precautions throughout the trial (post-menopausal women 
must be amenorrheic for at least 12 months to be considered of non-childbearing potential)
16. Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using highly effective methods of contraception 
during dosing and for 14 days after the final dose of nilotinib or imatinib. Patients using 
an oral hormonal contraception method should complete their monthly treatment course. 
Highly effective contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the 
subject). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception

Female sterilization (surgical bilateral oophorectomy with or without hysterectomy) 
or tubal ligation at least 6 weeks before taking study treatment. In case of 
oophorectomy alone, only when the reproductive status of the woman has been 
confirmed by follow-up hormone level assessment

Male sterilization (at least 6 months prior to screening). For female subjects on the 
study, the vasectomized male partner should be the sole partner for that subject

Combination of any two of the following (a+b or a+c, or b+c):
a. Use of oral, injected, or implanted hormonal methods of contraception or other 
forms of hormonal contraception that have comparable efficacy (failure rate <
1%), e.g. hormone vaginal ring or transdermal hormone contraception;
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS);
c. Barrier methods of contraception: condom or occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
In case of use of oral contraception, women should have been stable on the same pill 
for a minimum of 3 months before taking study treatment
17. Patients not able to understand and comply with study instructions and requirements
For those patients consenting to participate in the optional Stem cells ENESTPath substudy or 
in the ‘CML patient’s voice’ Italian substudy, the same exclusion criteria as for the 
ENESTPath study will apply.


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6
Treatment
6.1
Investigational treatment, other study treatment, supportive 
treatment
Study treatment: nilotinib (AMN107, Tasigna®)
Nilotinib will be supplied as 150 mg hard gelatin capsule. Nilotinib will not be dosed by 
weight or body surface area.
For detailed safety information, refer to the latest [AMN107 Investigator Brochure] and the 
approved product labeling.
6.1.1
Dosing regimen
This is an open-label study; therefore, all patients will receive a daily oral nilotinib dose of 
300 mg BID, given as two 150 mg capsules BID.
Patients eligible for randomization will either enter the TFR phase immediately or continue 
nilotinib for an additional 12 months (on a 1:1 basis).
Patients relapsing during the TFR phase will enter the nilotinib re-treatment phase of the study, 
and will be re-treated with the same dose of nilotinib as they were on before the TFR (i.e., the 
re-treatment dose will be nilotinib 300 mg BID or a lower dose of nilotinib if the dose was 
reduced in the consolidation phase before entering the TFR phase). The patient will 
subsequently remain on study until the patient completes the 5-year study period.
Nilotinib doses should be taken approximately 12 hours apart and must not be taken with food. 
The capsules should be swallowed whole with water. No food should be consumed for 
2 hours before the dose is taken and for at least 1 hour after.
For patients who are unable to swallow capsules, the content of each capsule may be 
dispersed in one teaspoon of apple sauce (puréed apple) and should be taken immediately. No 
more than one teaspoon of applesauce and no other food substance must be used.
The dose regimen can be decreased to 450 mg QD in the case of study drug-related 
non-hematologic and hematologic toxicities. Refer to Section 6.3.2 and Section 6.3.3 for 
further details.
Table 6-1
Dose and treatment schedule
Study treatments
Pharmaceutical form and 
route of administration
Dose
Frequency and/or 
regimen
Nilotinib
Capsule for oral use
300 mg BID
Daily
6.1.2
Ancillary treatments
Not applicable.
6.1.3
Rescue medication
Not applicable.


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6.1.4
Guidelines for continuation of treatment
In the 12-month induction phase and the subsequent 12- or 24-month consolidation phase of 
the study, patients may continue treatment until they progress, withdraw consent, experience 
unacceptable toxicity or start new therapy, or it is believed by the investigator to be in the best 
interest of the patient to exit the study.
Patients not achieving a sustained molecular response at 24 months from treatment start (and 
subsequently at 36 months from treatment start dependent of the randomization arm) will exit 
the study and will be treated at the discretion of the investigator according to standard practice. 
Survival information, stem cell transplantation, and information on the status of the patient’s 
disease (i.e., disease progression to AP/BP according to protocol definition, TKI treatment) 
will be collected until death, progression, or until 5 years from study entry, whichever comes 
first.
Patients relapsing during the TFR phase will enter the nilotinib re-treatment phase of the study, 
and will be re-treated with the same dose of nilotinib as they were on before the TFR phase 
(i.e. the re-treatment dose will be nilotinib 300 mg BID or a lower dose of nilotinib if this was 
reduced in the consolidation phase before entering the TFR phase). The patient will 
subsequently remain on study until the completion of the 5-year study period.
If a patient does not tolerate the nilotinib dose, dose modification guidelines specified in 
Table 6-2 and Table 6-3 should be followed.
6.1.5
Treatment duration
All patients will initially receive 24 months of nilotinib treatment unless they experience 
unacceptable toxicity, disease progression or withdrawal of consent, and/or treatment is 
discontinued at the discretion of the investigator.
Following these 24 months of treatment, patients in sustained ≥MR4.0 (as defined in Table 3-1)
for at least the last 12 months will be randomized to either suspend treatment immediately or 
receive a further 12 months of nilotinib therapy.
Patients not achieving a sustained molecular response at 24 months from treatment start (and 
subsequently at 36 months from treatment start depending on the randomization arm) will exit 
the study and will be treated at the discretion of the investigator according to standard practice. 
Survival information, stem cell transplantation, and information on the status of the patient’s 
disease (i.e., disease progression to AP/BC according to protocol definition, TKI treatment) 
will be collected until death, progression, or 5 years from study entry, whichever comes first.
Patients relapsing during the TFR phase will enter the nilotinib re-treatment phase of the study, 
and will be re-treated with the same dose of nilotinib as they were on before the TFR phase 
(i.e., the re-treatment dose will be nilotinib 300 mg BID or a lower dose of nilotinib if the 
dose was reduced in the consolidation phase before entering the TFR phase). The patient will 
subsequently remain on study until the patient completes the 5-year study period.
6.2
Dose escalation guidelines
Not applicable.


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6.3
Dose modifications
6.3.1
Dose modification and dose delay
For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments are 
permitted in order to allow the patient to continue the study treatment. Please refer to the dose 
modification guideline in Table 6-2 and Table 6-3 for details.
For the purpose of these dose-reduction guidelines, toxicity is defined as any AE that is, with 
reasonable likelihood according to investigator’s judgment, caused by the study drug.
According to International Conference on Harmonization (ICH) E6, the investigator is 
responsible for all trial-related medical decisions.
During and following a patient’s participation in a trial, the investigator should ensure that 
adequate medical care is provided to a patient for any AEs, including clinically significant 
laboratory values, related to the study drug. Any dose change must be recorded on the Dosage 
Administration Record Electronic Case Report Form (eCRF).
Dose escalation above the study dose of 300 mg BID (total 600 mg) nilotinib is not allowed. 
Dose adjustment should take place as soon as possible, as clinically indicated. Patients do not 
need to wait for a scheduled visit once clinical need has been determined.
If a dose reduction to 450 mg daily is required, the dose should be taken as 300 mg in the 
evening and 150 mg in the morning. If a dose reduction to 300 mg daily is required, the dose 
should be taken as 300 mg in the evening.
If multiple toxicities that require dose reduction are present, the greatest dose reduction 
schedule should be applied.
6.3.2
Dose-reduction guidelines for study drug-related non-hematologic 
toxicity
A summary of dose-reduction guidelines for study drug-related clinically significant 
non-hematologic toxicity is presented in Table 6-2.
These guidelines provide general principles and recommendations intended to support the 
investigator’s judgment and decisions about appropriate management of toxicity in the 
individual patient.
However, for those toxicities detailed in Table 6-2, the following rules (as detailed in the 
bullet points below) must be strictly followed:

Any non-hematological toxicity Grade 3 or 4 must be resolved within 28 days to ≤ Grade 
2 in order to resume study drug at the reduced dose. If a non-hematological toxicity Grade
3 or 4 does not resolve after 28 days, the patient must be discontinued from the study

If Grade 4 toxicity of the same type recurs despite dose reduction to 450 mg QD, the 
patient must be discontinued from the study

In case of Grade 3 pancreatitis, study drug treatment must be held and Novartis must be 
consulted immediately

In case of Grade 4 pancreatitis, study drug treatment must be permanently stopped and the 
patient must be discontinued from study


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
In case of Grade 4 liver toxicity, study drug treatment must be held and Novartis must be 
consulted immediately

In case of Grade 4 cardiac toxicity, study drug treatment must be permanently stopped and 
the patient must be discontinued from study.

In case of recurrent QTcF prolongation to > 480 msec despite dose reduction, the patient 
must be discontinued from the study unless the reason for QTcF prolongation can be 
corrected (such as discontinuing or replacing QT-prolonging concomitant drugs)
Patients who experience Grade 2/3/4 ischemic vascular or cardiovascular events should be 
referred for a cardiac or cardiovascular consult and management decisions (e.g. continue 
current treatment, dose reduction, or study discontinuation). Patients should be assessed for 
potential risk factors for the event, including causality secondary to CML therapy.
The Scientific Study Management Committee (SSMC) and DMC will be informed on a 
regular basis about the Grade 2/3/4 ischemic vascular or cardiovascular events occurring in
patients enrolled in the CAMN107AIC05 trial.


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Table 6-2
Summary of dose reduction guidelines for study drug-related 
clinically significant non-hematologic toxicity
Study drug and dose
Nilotinib 600 mg daily (as 300 mg BID)
General non-hematologic toxicity
Grade 2
(persisting > 7 days with 
optimal supportive care)
The dose of nilotinib may be reduced to 450 mg daily at the discretion of the 
investigator if clinically appropriate and in the best overall interest of the patient
≥ Grade 3
Hold therapy and resume nilotinib at next lower dose level after recovery to ≤ grade 2 
is seen
l→ 450 mg daily.
If recovery to ≤ grade 2 takes longer than 28 days, the patient must be discontinued 
from the study.
If grade 4 toxicity recurs despite dose reduction to 450 mg daily
l→ discontinue from the study.
Serum hypophosphatemia
Grade 2/3
Continue nilotinib at 300 mg BID and start phosphate supplementation.
Grade 4
Hold therapy and consult Novartis.
Serum creatinine
Grade 2
> 1.5-3.0 x ULN
The dose of nilotinib may be reduced to 450 mg daily at the discretion of the 
investigator if clinically appropriate and in the best overall interest of the patient.
≥ Grade 3
≥ 3.0 x ULN
Hold study drug and resume nilotinib at next lower dose level after recovery to ≤ 
grade 2 is seen
l→ 450 mg daily.
If recovery to ≤ grade 2 takes longer than 28 days, the patient must be 
discontinued from the study.
If grade 4 toxicity recurs despite dose reduction to 450 mg daily
l→ discontinue from the study.
Hepatobiliary [bilirubin, SGPT(AST), SGOT (ALT)]
Note: If hyperbilirubinemia is primarily due to the indirect bilirubin (with indirect bilirubin > direct bilirubin and direct 
bilirubin ≤ 1.5 x ULN and ALT ≤ grade 1, AST ≤ grade 1, alkaline phosphatase ALP ≤ grade 1, and hemolysis has 
been ruled out per institutional guidelines (e.g. by determination of haptoglobin), nilotinib may be continued at the 
same dose, at the discretion of the investigator.
Grade 2
The dose of nilotinib may be reduced to 450 mg daily at the discretion of the 
investigator if clinically appropriate and in the best overall interest of the patient.
≥ Grade 3
Hold study drug and resume nilotinib at next lower dose level after recovery to ≤ 
grade 2 is seen
l→ 450 mg daily.
If recovery to ≤ grade 2 takes longer than 28 days, the patient must be discontinued 
from the study
If grade 4 toxicity recurs despite dose reduction to 450 mg daily
l→ discontinue from the study.


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Study drug and dose
Nilotinib 600 mg daily (as 300 mg BID)
Pancreatitis (with abdominal symptoms plus lipase elevation)
Grade 2
Hold study drug and perform abdominal CT with contrast to exclude pancreatic 
pathology.
If CT is positive, continue to hold therapy and repeat CT at investigator’s discretion.
If CT is negative, re-start nilotinib at 450 mg daily after recovery to ≤ grade 1 is seen.
If recovery to ≤ grade 1 take longer than 28 days, the patient must be discontinued 
from the study.
If toxicity recurs
l→ discontinue from the study.
Grade 3
Hold therapy and consult Novartis.
Grade 4
Stop study drug. The patient must be discontinued from study.
Elevated lipase without symptoms
≥ Grade 3
Hold study drug.
Re-start nilotinib at 450 mg daily after recovery to ≤ grade 2 is seen.
If recovery to ≤ grade 2 takes longer than 28 days, the patient must be discontinued 
from the study.
If toxicity recurs without symptoms, consider appropriate diagnostic procedures, such 
as abdominal CT or ultrasound to exclude pancreatitis. After recovery to ≤ grade 2,
l→ continue dosing at 450 mg daily based on investigator’s discretion.
Diarrhea
Note: Antidiarrheal medication is recommended at the first sign of loose stools or overt diarrhea. If diarrhea 
cannot be controlled with optimal antidiarrheal treatments, take the following actions:
≥ Grade 3
Hold study drug and resume nilotinib at next lower dose level after recovery to ≤ 
grade 2 is seen
l→ 450 mg daily.
If recovery to ≤ grade 2 takes longer than 28 days, the patient must be discontinued 
from the study.
Vomiting
Note: Antiemetic medication should be withheld until the patient experiences ≥ grade 1 vomiting, then institute 
symptomatic therapy as appropriate. Antiemetics with the potential to prolong QT interval, such as domperidone,
must be avoided. If nausea and vomiting cannot be controlled with optimal antiemetic treatment, take the following 
actions: 
≥ Grade 3
Hold study drug and resume nilotinib at next lower dose level after recovery to ≤ 
grade 2 is seen
l→ 450 mg daily.
If recovery to ≤ grade 2 takes longer than 28 days, the patient must be discontinued 
from the study.


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Study drug and dose
Nilotinib 600 mg daily (as 300 mg BID)
Skin rash
Note: Institute symptomatic therapy as appropriate. If skin rash does not resolve with optimal treatments, take the 
following actions:
Grade 2
The dose of nilotinib may be reduced to 450 mg daily at the discretion of the 
investigator if clinically appropriate and in the best overall interest of the patient.
≥ Grade 3
Hold study drug and resume nilotinib at next lower dose level after recovery to ≤ 
grade 2 is seen
l→ 450 mg daily.
If recovery to ≤ grade 2 takes longer than 28 days, the patient must be discontinued 
from the study.
If grade 4 toxicity recurs despite dose reduction to 450mg daily
l→ discontinue.
Cardiac QTc prolongation
QTcF > 480 msec
Hold study drug when an ECG shows a QTcF > 480 msec.
In addition to the procedures below, the investigator should follow their local 
standards of practice and treatment guidelines for treating prolonged QT intervals.
●
Perform an analysis of serum potassium and magnesium, and if below lower limit 
of normal, correct with supplements to within normal limits.
●
Concomitant medication usage must be reviewed for their potential to inhibit 
CYP3A4 and/or to prolong the QT interval.
●
Perform a repeat ECG within 1 hour of the first QTcF of > 480 msec
●
If QTcF remains > 480 msec, repeat ECG as clinically indicated, but at least once 
a day until the QTcF returns to < 480 msec.
Study drug may be re-started, at same dose, if reason for elevation of QTcF is 
identified and corrected so that QTcF returns to < 450 msec and to within 20 msec of 
baseline within 2 weeks.
ECGs must be repeated 7 days after dose re-start for all patients who had therapy 
held due to QTcF > 480 msec.
If the QTcF is repeated and is more than 20 msec greater than baseline or between 
450 msec and 480 msec, the dose of study drug should be reduced to 450 mg 
daily
If QTcF of > 480 msec recurs or QTcF > 500 msec or prolongation of 60 msec to 
baseline value occurs, the patient is to be discontinued.
The investigator should contact Novartis regarding any questions that arise if a 
patient with QTcF prolongation should be maintained on study.
Note: QTcB can be used in centers that do not have the ability to automatically 
measure QTcF for QTc prolongation. 
In patients with a heart rate lower than 60 beats per minute, decisions are always 
based on QTcF because QTcB underestimates QT interval prolongation at heart 
rates below 60 beats per minute.


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Study drug and dose
Nilotinib 600 mg daily (as 300 mg BID)
Ischemic vascular or cardiovascular events
Grade 2*
Hold study drug and refer patient for assessment by a vascular or cardiovascular 
specialist.
Resume nilotinib next lower dose level after recovery to ≤ grade 1 is seen
l→ 450 mg daily.
If another recurrence
l→ discontinue.
If recovery to ≤ grade 1 takes longer than 28 days, the patient must be discontinued 
from the study.
Grade 3* or 4*
Hold study drug and refer patient for assessment by a vascular or cardiovascular 
specialist. Patients have to be discontinued whenever in the opinion of the 
investigator the AE is related to the study drug and other treatments could have a 
more favorable benefit/risk profile
* Patient should be assessed for potential risk factors for the event, including causality secondary to CML therapy
Cardiac “other”
Grade 2 or grade 3
Hold study drug and resume nilotinib at next lower dose level after recovery to ≤ 
grade 1 is seen
l→ 450 mg daily.
If recovery to ≤ grade 1 takes longer than 28 days, the patient must be discontinued 
from the study.
If grade 3 toxicity recurs despite dose reduction to 450mg daily
l→ discontinue.
Grade 4
Stop therapy. The patient must be discontinued from study.
6.3.3
Dose-reduction guidelines for study drug-related hematologic toxicity
A summary of dose-reduction guidelines for ≥grade 3 study drug-related hematologic toxicity 
as determined by the investigator is presented in Table 6-3.
No dose adjustments should be made for grade 1 or 2 hematologic toxicities. Any 
hematologic toxicity must be resolved to < grade 3 within 28 days in order to resume study 
drug. These guidelines provide some general principles as well as recommendations that are 
intended to support the investigator’s judgment and decision about the appropriate 
management of toxicity in the individual patient. However, if a hematologic toxicity does not 
resolve to ≤grade 2 within 28 days, the investigator should consult with the SSMC. Grade 1
or 2 hematologic AEs should not automatically be reported as serious AEs (SAEs) unless the 
event meets the criteria of a SAE as per the protocol.
In the case of any SAEs with a suspected causal relationship to study treatment, it should be 
reported as a SAE, nilotinib treatment may be discontinued, and the SSMC should be 
contacted for advice on patient management.


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Table 6-3
Summary of dose reduction guidelines for study drug-related 
hematologic toxicity
Toxicity
Grade 1
Grade 2
Grade 3
Grade 4
ANC or platelets
●
No dose 
reduction
●
No dose 
reduction
●
Grade 3/4 first and second time: Stop nilotinib, 
check at least weekly, resume 600 mg daily dose 
when < grade 3 (ANC > 1.0 x 109/L; platelets > 50 x
109/L)
●
Grade 3/4 third time: Stop nilotinib, check at least 
weekly, resume nilotinib at 450 mg daily dose when < 
grade 3 and at 600 mg daily dose after 1 week
●
Grade 3/4 fourth time: Stop nilotinib, check at 
least weekly, resume nilotinib at 300 mg daily dose 
when < grade 3 and at 600 mg daily dose after 1 
month
●
Grade 3/4 fifth or subsequent time: Stop nilotinib 
until < grade 3, then contact Novartis. It will be 
discussed with the SSMC whether nilotinib can be 
resumed or should be discontinued permanently
6.3.4
Suggested management of selected adverse events
The dose-reduction guidelines listed in Table 6-2 and Table 6-3 should be followed. 
Additional guidelines for management of patients are listed below.
Management of skin rash/pruritus
In most cases, rash is mild, self-limiting, and manageable with antihistamines or topical 
steroids. A short course of oral systemic corticosteroids may be initiated for the management 
of more severe cases, and may be continued until rash has resolved.
Management of edema
Patients should be monitored closely for peripheral edema and rapid weight gain. The use of 
diuretics may be initiated for the management of edema. Patients who develop ≥grade 3 
edema associated with cardiorespiratory symptoms should receive medical evaluations for the 
development of concomitant cardiac or respiratory diagnoses as indicated, such as an ECG
and a chest X-ray. Other medical tests may also be necessary to best manage the medical 
condition.
Management of liver toxicity
Routine liver function tests should be performed throughout the study as indicated in the visit 
schedule. Dose reduction may be warranted, and the decision to continue nilotinib needs to be 
made in light of the clinical situation (see dose-reduction Table 6-2).


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Dose modification for patients on anticoagulants
For patients on treatment with anticoagulants, the following guidelines will apply for 
thrombocytopenia:

If platelets ≤50 x 109/L, withhold treatment with study drug until recovery to at least 
> 75 x 109/L and resume treatment at same dose

If recurrence of platelets ≤50 x 109/L, then withhold treatment until recovery to at least 
> 75 x 109/L and resume treatment to a minimum of 300 mg/day

If the platelet count remains below 75 x 109/L, then nilotinib should be discontinued or 
management with anticoagulation therapy re-evaluated at the discretion of the investigator.
Every time TKI treatment has to be changed, international normalized ratio (INR) should be
checked at least twice weekly until stable INR values are established.
Management of cholesterol increases
Blood lipid panel tests should be performed at baseline and throughout the study as indicated 
in the visit schedule. If test results warrant intervention, investigators should follow their local 
standards of practice or treatment guidelines, which may recommend treatment even for grade 
1 cholesterol elevation. Before prescribing a lipid-lowering medication, the possibility of 
drug-drug interactions should be considered as some HMG-CoA reductase inhibitors are also 
metabolized via the CYP3A4 pathway.
Management of glucose increases
Blood glucose tests should be performed at baseline and throughout the study as indicated in 
the visit schedule. If blood glucose results warrant intervention, investigators should follow 
their local standards of practice and treatment guidelines in order to normalize blood glucose 
levels.
Management of other cardiac risk factors
Patients should be assessed or monitored for any other cardiac risk factors, such as family 
history, cardiovascular events in the past medical history, smoking, hypertension, and obesity. 
If the assessment for presence of any other cardiovascular risk factors warrants intervention, 
investigators should follow their local standards of practice or treatment guidelines.
Management of ischemic vascular or cardiovascular events
Newly diagnosed or worsened ischemic vascular or cardiovascular events have occurred in a 
relatively small number of CML-CP patients while on study medication. If a patient 
experiences such an AE, the investigator should ensure that the patient is assessed by a 
vascular or cardiovascular specialist. Further recommendations for the management of 
ischemic vascular or cardiovascular-related events are outlined in Table 6-2.


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Hepatitis B reactivation
Hepatitis B virus testing should be performed during the study as indicated in Section 7.1 to 
identify patients who may be at risk for Hepatitis B reactivation. Experts in liver disease and 
in the treatment of hepatitis B should be consulted for patients who test positive for hepatitis 
B virus during nilotinib treatment or for TFR patients who test positive for hepatitis B virus 
before treatment is re-initiated. Carriers of hepatitis B virus who require treatment with 
nilotinib should be closely monitored for signs and symptoms of active hepatitis B infection 
throughout therapy and for several months following termination of therapy.
Follow-up for toxicities
Patients whose treatment is permanently discontinued due to a study drug-related AE or 
abnormal laboratory value must be followed at least once a week for 4 weeks until resolution 
or stabilization of the event, whichever comes first.
All patients will be followed for serious adverse events (SAEs) for 30 days following 
premature discontinuation from any phases of the study or following end of participation as 
per protocol.
6.3.5
Guidelines for dose-re-escalation
Re-escalation of the dose of nilotinib to the 300 mg BID is permitted at the discretion of the
investigator. This applies to either dose reductions due to hematological or non-hematological
toxicities if the following criterion is met at least 28 days on treatment on the reduced dose.

All ≥ Grade 3 toxicities have resolved to ≤ Grade 2
6.4
Concomitant medications
6.4.1
Permitted concomitant therapy
In general, concomitant medications and therapies deemed necessary for the supportive care 
and safety of the patient are allowed, provided their use is documented in the patient records 
and on the appropriate case report form, including the medication’s duration (start and end 
dates or if continuing at final visit). These include blood and platelet transfusions for patients 
with anemia and with thrombocytopenia. The patient must be told to notify the investigational 
site about any new medications he/she takes after the start of the study drug. All medications 
(other than study drug) and significant non-drug therapies (including physical therapy and 
blood transfusions) administered during the study must be listed on the Prior and Concomitant 
Medications/Significant Non-Drug Therapies eCRF section.
The routine use of systemic corticosteroid therapy, except dexamethasone (as it is a strong 
CYP3A4 inducer), is permitted.
The use of prophylactic medication for vomiting is not recommended; however, antiemetic 
medication can be used as clinically indicated or when in the patient’s best interest.
The use of loperamide may be initiated for patients experiencing ≥grade 2 diarrhea, before 
dose interruption (e.g. Imodium®, with suggested dosing to start as 4 mg PO x 1, then 2 mg 
PO after each loose stool, up to a maximum of 16 mg/day).


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The use of hormonal contraception is permitted.
6.4.2
Permitted concomitant therapy requiring caution and/or action
The use of therapeutic coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon) 
is permitted; however, these should be given with caution. Low molecular weight heparin and 
heparin may be substituted for coumarin, and other medications for anticoagulation should be 
considered.
Patients on anticonvulsants should have regular monitoring of plasma concentration of these 
agents.
Cytochrome P450 3A4 substrates
Nilotinib is a moderate CYP3A4 inhibitor in vivo. Because of the thepotential risk for drug-
drug interactions, the systemic exposure of other drugs known to be sensitive substrates of 
CYP3A4 and also to have a narrow therapeutic index should be used with caution. A list of 
these drugs is listed in Appendix 14.1.1.
Antacid drugs:
Nilotinib has a pH-dependent solubility; therefore, in order not to impact nilotinib 
pharmacokinetics, administration of the following antacid drugs (if necessary) should be as 
follows:

H2 blocker (famotidine) may be administered approximately 10 hours before or 
approximately 2 hours after the dose of nilotinib,

Antacid (hydroxide/magnesium hydroxide/simethicone) may be administered 
approximately 2 hours before or approximately 2 hours after the dose of nilotinib.
6.4.3
Prohibited concomitant therapy
The concomitant administration of investigational drugs other than nilotinib is not allowed. 
The administration of any other anticancer agents, including chemotherapy and biologic 
agents, is not permitted except for anticancer treatments of newly diagnosed solid cancers (e.g. 
prostate cancer) that would not impact the level of minimal residual disease of patients. These 
patients may remain in study after consultation with Novartis.
The administration of other TKIs indicated for treatment of Ph+ CML is not allowed.
Every effort should be made NOT to administer strong CYP3A4 inhibitors. CYP3A4 
inhibitors may decrease the metabolism of nilotinib and thereby increase serum 
concentrations and increase exposure. If administration of a strong CYP3A4 inhibitor cannot 
be avoided during the study and the medication cannot be switched to an alternative therapy, 
study treatment must be STOPPED. Furthermore, increased awareness should be exercised 
when administering moderate inhibitors and/or multiple weak inhibitors. A list of these 
medications and inhibitor classifications can be found in Appendix 14.1.1; however, this list 
may not be comprehensive.


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Every effort should be made NOT to administer a QT interval-prolonging agent during 
the study. If when a patient is on nilotinib treatment, concomitant administration of an 
agent known to prolong the QT interval is required and cannot be switched to an 
alternative 
therapy, 
nilotinib 
must 
be 
STOPPED.
Please 
see 
http://crediblemeds.org/everyone/composite-list-all-qtdrugs/?rf=All for a list of agents that 
prolong the QT interval (this list may not be comprehensive).
Cardiac monitoring is required upon re-initiation of nilotinib therapy at any point.
Triplicate ECGs must be obtained before treatment re-initiation and 4 weeks after re-initiation 
of nilotinib therapy.
All patients must avoid grapefruit, star fruit, pomegranate, and Seville oranges during the 
study. The juices and products containing these fruits must also be avoided.
6.5
Patient numbering, treatment assignment and randomization
6.5.1
Patient numbering
Each patient is identified in the study by a patient number (Patient No.) that is assigned when 
the patient is first enrolled for screening and is retained as the primary identifier for the patient 
throughout his/her entire participation in the trial. The Patient No. consists of the Center 
Number (Center No.) (as assigned by Novartis to the investigative site) with a sequential 
patient number suffixed to it, so that each subject is numbered uniquely across the entire 
database. Upon signing the informed consent form (ICF), the patient is assigned to the next 
sequential Patient No. available to the investigator through the Oracle Clinical RDC interface. 
Once assigned, the Patient No. must not be reused for any other subject, and the Patient No. 
for that individual must not be changed, even if the patient is re-screened.
If the patient fails to be randomized for any reason, the reason will be entered into the End of 
Consolidation Phase page.
6.5.2
Treatment assignment and randomization
All patients will initially receive 24 months of open-label nilotinib treatment. Following this, 
eligible patients (i.e., those deemed to have achieved sustained ≥MR4.0) will be randomized to 
one of the two study arms (see Section 4.1 and Section 6.1) in a ratio of 1:1 on a continued 
open-label basis.
A randomization list will be produced by or under the responsibility of Novartis using a 
validated system that automates the random assignment of treatment groups to randomization 
numbers in the specified ratio.
6.5.3
Treatment blinding
This is an open-label trial and blinding is not applicable.


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6.6
Study drug supply
6.6.1
Study drug preparation and dispensation
No specific preparation instructions are applicable to nilotinib. The investigational agent will 
be dispensed by site study personnel on an outpatient basis (see Table 6-4 for details). Patients 
will be instructed on how to take study medication, and will be provided with an adequate 
supply of study drug for self-administration at home until at least their next scheduled study 
visit. Records of drug formulation, batch number, and number of capsules dispensed, received, 
and returned must be recorded.
The study medication is to be stored at room temperature (< 30oC) in a secure, locked area 
while under the responsibility of the investigator. Receipt and dispensing of study medication 
must be recorded by an authorized person at the investigator’s site. The storage temperature 
should be checked weekly, and recorded on a Temperature Log.
Medication labels will be in the local language and will comply with the legal requirements of 
each country.
Table 6-4
Preparation and dispensing
Study treatment
Dispensing
Preparation
Nilotinib
Capsules and instructions for administration are dispensed by study 
personnel on an outpatient basis.
Patients will be provided with an adequate supply of nilotinib for 
self-administration at home until at least their next scheduled study visit.
Not applicable
6.6.2
Study drug packaging and labeling
Nilotinib will be supplied by Novartis as 150 mg hard gelatin capsules. Medication labels will 
be in the local language and will comply with the legal requirements of each country.
6.6.3
Drug supply and storage
Study medication must be received by a designated person at the study site and be kept in a 
secured location to which only the investigator and designated assistants have access.
Table 6-5
Packaging and labeling
Study treatments
Packaging
Labeling (and dosing frequency)
AMN107 (nilotinib)
Capsules in bottles
Labeled as “AMN107”
AMN107 (nilotinib)
Capsules in blister
Labeled as Tasigna® “nilotinib”
6.6.4
Study drug compliance and accountability
6.6.4.1
Study drug compliance
All dosages prescribed to the patient and all dose changes during the study must be recorded 
on the Dosage Administration Record eCRF.


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6.6.4.2
Study drug accountability
The Investigator or designee must maintain an accurate record of the prescribing of study 
treatment in a drug accountability ledger. Patients will be asked to return all unused study 
drug at each visit in order to allow the investigator and/or study personnel to complete a drug 
accountability check.
At study close-out and as appropriate during the course of the study, the investigator will 
return all used and unused study treatment, packaging, drug labels, and a copy of the 
completed drug accountability ledger to the Novartis monitor or to the Novartis address 
provided in the investigator folder at each site.
6.6.5
Disposal and destruction
The drug supply can be destroyed at the local Novartis facility, Drug Supply group, or third 
party, as appropriate, and according to local regulations and Novartis procedure.
7
Visit schedule and assessments
7.1
Study flow and visit schedule
Table 7-1, Table 7-2, Table 7-3, and Table 7-4 list all of the assessments applicable to each 
phase of the study and indicate with an “X”, when visits are to be performed.
All data obtained from these assessments must be supported in the patient’s source 
documentation. The table indicates which assessments produce data to be entered into the 
database (D) or remain in source documents only (S) (“Category” column).
All assessments should be performed within ± 7 days of the time points specified.
For patients consenting to participate to the ‘CML patient’s voice’ Italian substudy please 
refer to [Post Text Supplement 1].
Hepatitis B testing will be performed once and only once, at the next possible visit when 
patient is on treatment or before treatment is re-initiated (see Section 7.2.2.4.5 for details).


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Table 7-1
Visit evaluation schedule 1: screening and induction/consolidation phase
Category
Screening
Re-Screening
Nilotinib Induction/Consolidation Phase
End of Phase 
(EOP) Visit a,b,c
Safety 
Follow-up 
/Study 
Evaluation 
Completion
Follow-up 
I,j
Visit number
Screening
Re-
Screening
Baseline
VD15
VM1
V1
V2
V3
V4-V8
V9-
Randomi
zation
V201-V204
(Only 
applicable to 
Arm 2)
a: End of Phase
(EOP = V400)
EOS
V501-V520
(if 
applicable)
Day/week/
month of 
study
D −28 to 0
D1
D15
m,g
M1
m,g
M3g
M6g
M9g
M12, 
then 
every 3
months 
until 
M24b,g
Within 
15 
working 
days 
from 
M24 visit
M27, then 
every 
3 months until 
M36b,d,g
If patient 
withdraws 
during
induction/conso
lidation phase 
(at any visits 
from baseline to 
V8 for Arm 1 or 
to V204 for Arm 
2).
30 days 
following the 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
Obtain 
informed 
consent
D
x
X
Inclusion/excl
usion criteria
D
x
X
Demographic
s
D
x
X
Relevant 
medical 
history/current 
medical 
conditionso
D
x
X


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Screening
Re-Screening
Nilotinib Induction/Consolidation Phase
End of Phase 
(EOP) Visit a,b,c
Safety 
Follow-up 
/Study 
Evaluation 
Completion
Follow-up 
I,j
Visit number
Screening
Re-
Screening
Baseline
VD15
VM1
V1
V2
V3
V4-V8
V9-
Randomi
zation
V201-V204
(Only 
applicable to 
Arm 2)
a: End of Phase
(EOP = V400)
EOS
V501-V520
(if 
applicable)
Day/week/
month of 
study
D −28 to 0
D1
D15
m,g
M1
m,g
M3g
M6g
M9g
M12, 
then 
every 3
months 
until 
M24b,g
Within 
15 
working 
days 
from 
M24 visit
M27, then 
every 
3 months until 
M36b,d,g
If patient 
withdraws 
during
induction/conso
lidation phase 
(at any visits 
from baseline to 
V8 for Arm 1 or 
to V204 for Arm 
2).
30 days 
following the 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
Disease 
history 
(diagnosis of 
CML)p
D
x
Prior/current 
antineoplastic 
therapy
D
x
X
Echocardiogr
am
D
x
X
ECG
D
x
X
xm
xm
x
x
Edinburgh 
Claudication 
Questionnaire
D
x
X
x
xn
xn


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Screening
Re-Screening
Nilotinib Induction/Consolidation Phase
End of Phase 
(EOP) Visit a,b,c
Safety 
Follow-up 
/Study 
Evaluation 
Completion
Follow-up 
I,j
Visit number
Screening
Re-
Screening
Baseline
VD15
VM1
V1
V2
V3
V4-V8
V9-
Randomi
zation
V201-V204
(Only 
applicable to 
Arm 2)
a: End of Phase
(EOP = V400)
EOS
V501-V520
(if 
applicable)
Day/week/
month of 
study
D −28 to 0
D1
D15
m,g
M1
m,g
M3g
M6g
M9g
M12, 
then 
every 3
months 
until 
M24b,g
Within 
15 
working 
days 
from 
M24 visit
M27, then 
every 
3 months until 
M36b,d,g
If patient 
withdraws 
during
induction/conso
lidation phase 
(at any visits 
from baseline to 
V8 for Arm 1 or 
to V204 for Arm 
2).
30 days 
following the 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
Physical 
examination
D
x
X
x*
x
x
x
x
x
x
x
Vital signs
D
x
X
x*
x
x
x
x
x
x
x
ECOG 
performance 
status
D
x
X
x*
x
x
x
x
x
x
Hematology
D
x
X
x*
xm
xm
x
x
x
x
x
x
X
Clinical 
chemistry
D
x
X
x*
xm
xm
x
x
x
x
x
x
X
Serum 
pregnancy 
test (if 
applicable)
D
x
X
x*
x
X


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Screening
Re-Screening
Nilotinib Induction/Consolidation Phase
End of Phase 
(EOP) Visit a,b,c
Safety 
Follow-up 
/Study 
Evaluation 
Completion
Follow-up 
I,j
Visit number
Screening
Re-
Screening
Baseline
VD15
VM1
V1
V2
V3
V4-V8
V9-
Randomi
zation
V201-V204
(Only 
applicable to 
Arm 2)
a: End of Phase
(EOP = V400)
EOS
V501-V520
(if 
applicable)
Day/week/
month of 
study
D −28 to 0
D1
D15
m,g
M1
m,g
M3g
M6g
M9g
M12, 
then 
every 3
months 
until 
M24b,g
Within 
15 
working 
days 
from 
M24 visit
M27, then 
every 
3 months until 
M36b,d,g
If patient 
withdraws 
during
induction/conso
lidation phase 
(at any visits 
from baseline to 
V8 for Arm 1 or 
to V204 for Arm 
2).
30 days 
following the 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
Serology 
(Hepatitis B 
testing)
D
X ONLY once after patient is consented to amendment 04
Urine 
pregnancy 
testk (if 
applicable)
D
xk
xk
xk
xk
xk
xk
Urine 
analysisq
D
x
X
x*
Peripheral 
blood BCR-
ABL RQ-PCR 
result from 
local 
laboratory
D
xe


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Screening
Re-Screening
Nilotinib Induction/Consolidation Phase
End of Phase 
(EOP) Visit a,b,c
Safety 
Follow-up 
/Study 
Evaluation 
Completion
Follow-up 
I,j
Visit number
Screening
Re-
Screening
Baseline
VD15
VM1
V1
V2
V3
V4-V8
V9-
Randomi
zation
V201-V204
(Only 
applicable to 
Arm 2)
a: End of Phase
(EOP = V400)
EOS
V501-V520
(if 
applicable)
Day/week/
month of 
study
D −28 to 0
D1
D15
m,g
M1
m,g
M3g
M6g
M9g
M12, 
then 
every 3
months 
until 
M24b,g
Within 
15 
working 
days 
from 
M24 visit
M27, then 
every 
3 months until 
M36b,d,g
If patient 
withdraws 
during
induction/conso
lidation phase 
(at any visits 
from baseline to 
V8 for Arm 1 or 
to V204 for Arm 
2).
30 days 
following the 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
Peripheral 
blood BCR-
ABL RQ-PCR 
(performed in 
a EUTOS 
standardized 
laboratory)
D
xh
X
xh
xh
xh
xh
xh
xc,h
Bone marrow 
assessments/ 
cytogenetics
D
xf
xf
In case of loss of MMR or in case patient has not achieved MMR and it is 
deemed clinically indicated by the investigator
Mutational 
analysis
D
In case of loss of MMR or in case patient has not achieved MMR and it is 
deemed clinically indicated by the investigator


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Screening
Re-Screening
Nilotinib Induction/Consolidation Phase
End of Phase 
(EOP) Visit a,b,c
Safety 
Follow-up 
/Study 
Evaluation 
Completion
Follow-up 
I,j
Visit number
Screening
Re-
Screening
Baseline
VD15
VM1
V1
V2
V3
V4-V8
V9-
Randomi
zation
V201-V204
(Only 
applicable to 
Arm 2)
a: End of Phase
(EOP = V400)
EOS
V501-V520
(if 
applicable)
Day/week/
month of 
study
D −28 to 0
D1
D15
m,g
M1
m,g
M3g
M6g
M9g
M12, 
then 
every 3
months 
until 
M24b,g
Within 
15 
working 
days 
from 
M24 visit
M27, then 
every 
3 months until 
M36b,d,g
If patient 
withdraws 
during
induction/conso
lidation phase 
(at any visits 
from baseline to 
V8 for Arm 1 or 
to V204 for Arm 
2).
30 days 
following the 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
Determination 
of Ph+ stem 
cells in bone 
marrowl 
D
x
X
At V8
At V204
Adverse 
events
D
Continuous
x
x (SAE)


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Screening
Re-Screening
Nilotinib Induction/Consolidation Phase
End of Phase 
(EOP) Visit a,b,c
Safety 
Follow-up 
/Study 
Evaluation 
Completion
Follow-up 
I,j
Visit number
Screening
Re-
Screening
Baseline
VD15
VM1
V1
V2
V3
V4-V8
V9-
Randomi
zation
V201-V204
(Only 
applicable to 
Arm 2)
a: End of Phase
(EOP = V400)
EOS
V501-V520
(if 
applicable)
Day/week/
month of 
study
D −28 to 0
D1
D15
m,g
M1
m,g
M3g
M6g
M9g
M12, 
then 
every 3
months 
until 
M24b,g
Within 
15 
working 
days 
from 
M24 visit
M27, then 
every 
3 months until 
M36b,d,g
If patient 
withdraws 
during
induction/conso
lidation phase 
(at any visits 
from baseline to 
V8 for Arm 1 or 
to V204 for Arm 
2).
30 days 
following the 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
Concomitant 
medications
D
Continuous
x
x (SAE)
Study Drug 
administration
D
Continuous
TKI treatment
D
x
Progression 
to AP/BC
D
x
Stem cell 
transplant 
information
D
x
Survival 
follow-up
D
x


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Screening
Re-Screening
Nilotinib Induction/Consolidation Phase
End of Phase 
(EOP) Visit a,b,c
Safety 
Follow-up 
/Study 
Evaluation 
Completion
Follow-up 
I,j
Visit number
Screening
Re-
Screening
Baseline
VD15
VM1
V1
V2
V3
V4-V8
V9-
Randomi
zation
V201-V204
(Only 
applicable to 
Arm 2)
a: End of Phase
(EOP = V400)
EOS
V501-V520
(if 
applicable)
Day/week/
month of 
study
D −28 to 0
D1
D15
m,g
M1
m,g
M3g
M6g
M9g
M12, 
then 
every 3
months 
until 
M24b,g
Within 
15 
working 
days 
from 
M24 visit
M27, then 
every 
3 months until 
M36b,d,g
If patient 
withdraws 
during
induction/conso
lidation phase 
(at any visits 
from baseline to 
V8 for Arm 1 or 
to V204 for Arm 
2).
30 days 
following the 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
* These assessments should be performed only if the Day 1 visit occurred > 8 days after the screening visit.
a For patients withdrawing from the induction/consolidation phase, this visit should be performed within 15 working days of stopping study treatment.
b If a patient has already had two results with less than MR4.0 by Month 24/36, the patient is not eligible for randomization, and in this case the 24 or the 36 months visit 
should be performed as the EOP visit, including all the assessments of EOP.
c For all other patients, this visit should be performed within 15 working days of the M24 visit to check and confirm their eligibility for randomization, or within 15 working 
days of the M36 visit for patients randomized to study Arm 2 to check and confirm their eligibility to enter the TFR phase-for these eligibility checks at Visits 9/205, no RQ-
PCR evaluation will be done.
d Assessment schedule for patients randomized to receive 24 months of nilotinib consolidation treatment.
e An RQ-PCR result obtained from local laboratory within 14 weeks of signing the ICF is acceptable.
f To be performed only if the patient to deemed to be in less than MMR, as determined by the local laboratory or EUTOS BCR-ABL RQ-PCR assessment: no need to 
re-perform the bone marrow assessment at screening visit if the cytogenetic assessment result shows CCyR and this bone marrow assessment was obtained within 
14 weeks of signing the ICF.
g A “visit window” of ± 7 days is allowed.
h If patients consent, the remaining blood samples after analysis will be stored for biomarker assessment
i For patients withdrawing from the induction/consolidation phase, this follow-up should be done until patient completes 5 years from study entry (starting 3 months after 
the EOP visit).


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Screening
Re-Screening
Nilotinib Induction/Consolidation Phase
End of Phase 
(EOP) Visit a,b,c
Safety 
Follow-up 
/Study 
Evaluation 
Completion
Follow-up 
I,j
Visit number
Screening
Re-
Screening
Baseline
VD15
VM1
V1
V2
V3
V4-V8
V9-
Randomi
zation
V201-V204
(Only 
applicable to 
Arm 2)
a: End of Phase
(EOP = V400)
EOS
V501-V520
(if 
applicable)
Day/week/
month of 
study
D −28 to 0
D1
D15
m,g
M1
m,g
M3g
M6g
M9g
M12, 
then 
every 3
months 
until 
M24b,g
Within 
15 
working 
days 
from 
M24 visit
M27, then 
every 
3 months until 
M36b,d,g
If patient 
withdraws 
during
induction/conso
lidation phase 
(at any visits 
from baseline to 
V8 for Arm 1 or 
to V204 for Arm 
2).
30 days 
following the 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
j For patients who are not eligible for randomization (have already had two results with less than MR4.0 by Month 24/36), this follow-up period should be done until patient 
completes 5 years from study entry (starting 3 months after the EOP visit).
k Urine pregnancy test will be performed on a monthly basis from Month 1 onwards, and test results will be documented in a diary by the patient.
l This assessment is only applicable to those patients consenting to participate in the optional Stem cells ENESTPath substudy. It will be performed at the screening visit, 
at Visit 8 , and (for patients included in Arm 2) at Visit 204.
m Optional visits at Day 15 and Month 1 based on local requirements or as clinically indicated.
n Edinburgh Claudication Questionnaire to be performed every 6 months during the induction/consolidation phase (at Screening and Months 6, 12, 18, 24, 30, and 36 as 
applicable depending on randomization).
o Includes smoking history and family history of cardiovascular events.
p Including if a previous stopping attempt under imatinib was performed and for how long the patient was in TFR.
q: only in patients with known diabetes mellitus (see Section 7.2.2.4.4)


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Table 7-2
Visit evaluation schedule 2: Nilotinib TFR phase (Arm 1)
Category
Nilotinib TFR phase
End of 
Phase 
(EOP)a
visit
Safety 
Follow-up/ 
Study 
Evaluation 
Completion
Follow-upe
Visit Number
V101-V106
V107-V109
V110-V117
EOP = 
401
EOS
V501-V520
(if applicable)
Day/week/month of study in TFR 
phase
M1, then every 
month until M6c
M8, then every 
2 months until 
M12c
M15, then every 
3 months until
M36c,d
If patient 
withdraw 
during
TFR (at 
any visits 
from 
V101 to 
V117)
30 days 
following 
EOP visit
Every 3 months 
± 21 days until 
5 years from 
study entry
Physical examination
D
Every 6 months
x
Vital signs
D
Every 6 months
x
ECOG performance status
D
Every 6 months
x
ECG
D
As needed
x
Edinburgh Claudication Questionnaire
D
Every 6 months
Hematology
D
X
x
x
x
Clinical chemistry
D
Every 6 months
x
Serum pregnancy test (if applicable)
D
x
Urine pregnancy testf (if applicable)
D
xf
xf
xf
Peripheral blood BCR-ABL RQ-PCRb
D
xb
xb
xb
xb
Bone marrow assessments/cytogenetics
D
In case of loss of MMR
Mutational analysis
D
In case of loss of MMR
Adverse events
D
Continuous
x
x
Determination of Ph+ stem cells in bone 
marrowg
D
If patient relapses, before re-starting treatment with nilotinib


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Nilotinib TFR phase
End of 
Phase 
(EOP)a
visit
Safety 
Follow-up/ 
Study 
Evaluation 
Completion
Follow-upe
Visit Number
V101-V106
V107-V109
V110-V117
EOP = 
401
EOS
V501-V520
(if applicable)
Day/week/month of study in TFR 
phase
M1, then every 
month until M6c
M8, then every 
2 months until 
M12c
M15, then every 
3 months until
M36c,d
If patient 
withdraw 
during
TFR (at 
any visits 
from 
V101 to 
V117)
30 days 
following 
EOP visit
Every 3 months 
± 21 days until 
5 years from 
study entry
Concomitant medications
D
Continuous
x
x
TKI treatment
D
x
Progression to AP/BC
D
x
Stem cell transplant information
D
x
Survival follow-up
D
x
a Applicable to all patients withdrawing from the TFR phase and not starting the nilotinib re-treatment phase as per protocol.
b Performed in a EUTOS standardized laboratory. 
c A “visit window” of ± 7 days is allowed.
d For patients completing the TFR phase per protocol, the last scheduled visit of the TFR phase will be the EOP visit (V117 [M36] of the TFR phase).
e For patients withdrawing from the TFR phase and not starting the nilotinib re-treatment phase as per protocol, this follow-up should be done until patient completes 5 
years from study entry (starting 3 months after EOP phase visit).
f Urine pregnancy test will be performed monthly, and test results will be documented in a diary by the patient.
g This assessment is only applicable to those patients consenting to participate in the optional Stem cells ENESTPath substudy. 


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Table 7-3
Visit evaluation schedule 3: Nilotinib TFR phase (Arm 2)
Category
Nilotinib TFR phase
End of 
Phase 
(EOP)a
visit
Safety 
Follow-up/ 
Study 
Evaluation 
Completion
Follow-upe
Visit Number
V205
V206-V211
V212-V214
V215-V218
EOP = 
401
EOS
V501-V520
(if 
applicable)
Day/week/month of study 
in TFR phase
Eligibility
M1, then every month until M6c
M8, then 
every 
2 months 
until M12c
M15, then 
every 
3 months 
until
M24c,d
If patient 
withdraw 
during
TFR (at 
any 
visits 
from 
V101 to 
V117) 
30 days 
following 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
Physical examination
D
x
Every 6 months
x
Vital signs
D
x
Every 6 months
x
ECOG performance status
D
Every 6 months
x
ECG
D
As needed
x
Edinburgh Claudication 
Questionnaire
D
Every 6 months
Hematology
D
x
X
x
x
x
Clinical chemistry
D
x
Every 6 months
x
Serum pregnancy test
(if applicable)
D
x
x
Urine pregnancy testf
(if applicable)
D
xf
xf
xf
Peripheral blood BCR-ABL 
RQ-PCRb
D
xb
xb
xb
xb


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Nilotinib TFR phase
End of 
Phase 
(EOP)a
visit
Safety 
Follow-up/ 
Study 
Evaluation 
Completion
Follow-upe
Visit Number
V205
V206-V211
V212-V214
V215-V218
EOP = 
401
EOS
V501-V520
(if 
applicable)
Day/week/month of study 
in TFR phase
Eligibility
M1, then every month until M6c
M8, then 
every 
2 months 
until M12c
M15, then 
every 
3 months 
until
M24c,d
If patient 
withdraw 
during
TFR (at 
any 
visits 
from 
V101 to 
V117) 
30 days 
following 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
Bone marrow 
assessments/ cytogenetics
D
In case of loss of MMR
Mutational analysis
D
In case of loss of MMR
Adverse events
D
Continuous
x
x
Determination of Ph+ stem 
cells in bone marrowg
D
If patient relapses, before re-starting treatment with nilotinib
Concomitant medications
D
Continuous
x
x
TKI treatment
D
x
Progression to AP/BC
D
x
Stem cell transplant 
information
D
x
Survival follow-up
D
x


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Amended Protocol Version 04 (Clean)
Protocol No. CAMN107AIC05
Category
Nilotinib TFR phase
End of 
Phase 
(EOP)a
visit
Safety 
Follow-up/ 
Study 
Evaluation 
Completion
Follow-upe
Visit Number
V205
V206-V211
V212-V214
V215-V218
EOP = 
401
EOS
V501-V520
(if 
applicable)
Day/week/month of study 
in TFR phase
Eligibility
M1, then every month until M6c
M8, then 
every 
2 months 
until M12c
M15, then 
every 
3 months 
until
M24c,d
If patient 
withdraw 
during
TFR (at 
any 
visits 
from 
V101 to 
V117) 
30 days 
following 
EOP visit
Every 3 
months ± 
21 days 
until 
5 years 
from study 
entry
a Applicable to patients withdrawing from the TFR phase and not starting the nilotinib re-treatment phase as per protocol.
b Performed in a EUTOS standardized laboratory
.
c A “visit window” of ± 7 days is allowed.
d For patients completing the TFR phase per protocol the last scheduled visit of the TFR phase will be the EOP visit (V117 [M36] of the TFR phase).
e For patients withdrawing from the TFR phase and not starting the nilotinib re-treatment phase as per protocol, this follow-up should be done until patient completes 5 
years from study entry (starting 3 months after EOP phase visit).
f Urine pregnancy test will be performed monthly, and test results will be documented in a diary by the patient.
g This assessment is only applicable to those patients consenting to participate in the optional Stem cells ENESTPath substudy.


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Table 7-4
Visit evaluation schedule 4: Nilotinib re-treatment phase (if applicable)
Category
Nilotinib Re-treatment
End of Phase 
(EOP) visita,e
Safety 
Followup/Study 
Evaluation 
Completion
Follow-upf
Visit number
V301
V302
V303
V304-314 
(as 
applicable)
a: EOP = V402
EOS
V501-V520 
(as 
applicable)
Day/week/month of study in 
re-treatment phase
Day 1
W6d
M3d
M6, then 
every 
3 months 
until 5 years 
from study 
entryd,e
Within 15 
working days 
of last dose
30 days 
following the 
EOP visit
Every 3 
months ± 21 
days until 5 
years from 
study entry
Physical examination
S
x c
x
x
x
Vital signs
D
x c
x
x
x
ECOG performance status
D
x c
x
x
x
Peripheral blood BCR-ABL RQ-PCRb
D
xb
xb
xb
xb
ECG
D
x c
x
x
Edinburgh Claudication Questionnaire
S
x c,h
xh
Hematology
D
x c
x
x
x
Clinical chemistry
D
x c
x
x
x
Mutational analysis
D
In case of 
loss of MMR
As needed
Serum pregnancy test (if applicable)
D
x c
x
Serology (Hepatitis B testing)
D
X ONLY once after patient is consented to amendment 04
Urine pregnancy testg (if applicable)
D
xg
xg
Adverse events/SAE
D
Continuous
x
x (SAE)
Concomitant medications
D
Continuous
x
x (SAE)


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Category
Nilotinib Re-treatment
End of Phase 
(EOP) visita,e
Safety 
Followup/Study 
Evaluation 
Completion
Follow-upf
Visit number
V301
V302
V303
V304-314 
(as 
applicable)
a: EOP = V402
EOS
V501-V520 
(as 
applicable)
Day/week/month of study in 
re-treatment phase
Day 1
W6d
M3d
M6, then 
every 
3 months 
until 5 years 
from study 
entryd,e
Within 15 
working days 
of last dose
30 days 
following the 
EOP visit
Every 3 
months ± 21 
days until 5 
years from 
study entry
TKI treatment information
D
x
Progression to AP/BC
D
x
Stem cell transplant information
D
x
Survival follow-up
D
x
a Applicable to patients withdrawing from the nilotinib re treatment phase before completing the 5-year study period.
b Performed in a EUTOS standardized laboratory. 
.
c The assessment schedule for Day 1 should be completed for those tests that were not performed on the day of confirmed loss of MR4 0, or loss of MMR.
d A “visit window” of ± 7 days is allowed.
e For patients completing the nilotinib re-treatment phase per protocol, the last scheduled visit of the nilotinib re-treatment phase in order to complete the 5 years from 
study entry will be the EOP visit (V314).
f For patients withdrawing from the nilotinib re-treatment phase before completing the 5-year study period, this follow-up should be done until patient completes 5 years 
from study entry (starting 3 months after EOP phase visit).
g Urine pregnancy test will be performed monthly and test results will be documented in a diary by the patient.
h Edinburgh Claudication Questionnaire to be performed every 6 months during the nilotinib re-treatment phase (Day 1 until patient completes 5 years from study entry as 
applicable).


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7.1.1
Pre-screening assessment
Not applicable.
7.1.2
Screening
Written informed consent must be obtained before any study specific medical procedures are 
performed. A screening visit should occur between study days -28 and 0.
During the screening visit, inclusion and exclusion criteria will be assessed. For details of
assessments required during screening, please refer to Table 7-1.
A recent RQ-PCR result must be available to demonstrate a BCR-ABL level of <MR4.0.
If a RQ-PCR was performed by a local laboratory within 14 weeks of signing the informed
consent (ICF), a RQ-PCR peripheral blood sample should be sent to a EUTOS standardized 
laboratory for confirmation of the baseline BCR-ABL levels.
If a RQ-PCR result from a local laboratory is not available within 14 weeks of signing the 
informed consent (ICF), RQ-PCR peripheral blood samples (two separate vials) for the local 
and the EUTOS standardized laboratory assessment should be collected at the same time.
The decision tree for protocol entry based on the molecular response assessment is as follows:

Patients with <MR4.0 as measured in the local laboratory and confirmed in the EUTOS 
standardized laboratory are eligible

Patients with <MR4.0 as measured in the local laboratory, but with ≥MR4.0 as assessed by a 
EUTOS standardized laboratory, are not eligible, and will be considered as screening 
failures

Patients with ≥MR4.0 as measured in the local laboratory, but with <MR4.0 as assessed by a
EUTOS standardized laboratory, are eligible

Patients with ≥MR4.0 as measured in the local laboratory and confirmed by a EUTOS 
standardized laboratory, are not eligible, and will be considered as screening failures.
If BCR-ABL transcript level at screening is <MMR (less than MR3.0) as assessed at a local 
and/or EUTOS standardized laboratory, a bone marrow biopsy/aspirate needs to be performed 
to assess the patient’s cytogenetic response, unless a bone marrow assessment confirming 
CCyR was obtained within 14 weeks of signing the ICF.
Only patients who are shown to be in CCyR are eligible for ENESTPath. Patients without 
CCyR are considered screening failures.
Every effort should be made to collect data on the risk assessment factors at the time of CML 
diagnosis for each patient enrolled in this study (eosinophils, basophils, spleen size, platelets, 
age).
Re-screening of a patient will be allowed for this study. As long as a patient meets all 
inclusion criteria and none of the exclusion criteria, he/she will be enrolled in this study after 
re-screening.


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7.1.2.1
Eligibility screening
Patients must meet all inclusion and none of the exclusion criteria in order to be eligible for 
the study. Patient eligibility will be confirmed by the investigative staff and captured within 
the source documents maintained at the site. This information will be made available during 
planned interim monitoring visits and compared against the clinical database for accuracy.
7.1.2.2
Information to be collected on screening failures
A patient who signs an informed consent form (ICF) but fails to commence treatment for any 
reason will be considered a screening failure. The reason for not being started on treatment 
will be entered on the Screening Log eCRF page. Demographic information, informed 
consent date, and inclusion/exclusion pages must also be completed for screening failure 
patients. No other data will be entered into the clinical database for patients who are screening 
failures, unless the patient experienced a SAE during the screening phase (see Section 8 for 
SAE reporting details).
7.1.2.3
Patient demographics and other screening characteristics
After the patient has signed the ICF, the following assessments will be performed at the 
screening visit:

Demographics (age, gender, race)

Relevant medical history, including current medical conditions, smoking history, and 
family history of cardiovascular events;

Disease history (diagnosis of CML), and whether a previous stopping attempt under 
imatinib was performed and for how long the patient was in TFR

Prior/current antineoplastic therapy

Prior/concomitant medications

Physical examination (see Section 7.2.2.1 for details)

Vital signs (see Section 7.2.2.2 for details)

ECOG performance status

BCR-ABL RQ-PCR result from local laboratory, performed within 14 weeks of signing 
the ICF

Peripheral blood for RQ-PCR to establish a baseline BCR-ABL value will be collected 
and sent to a EUTOS standardized laboratory. If the patient consents, any blood remaining 
after analysis will be stored at a EUTOS standardized laboratory;

Laboratory evaluations:

Hematology (see Section 7.2.2.4.1 for details)

Clinical chemistry (see Section 7.2.2.4.2 for details)

Urine analysis (see Section 7.2.2.4.4 for details)

Serum pregnancy test and discussion of contraception measures to be taken (if 
applicable) (see Section 7.2.2.4.3 for details)


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Potassium, calcium, magnesium, and/or sodium supplements may be given to correct values 
that are < lower limit of normal (LLN). Post-correction values must not be deemed to be a 
clinically significant abnormality prior to patients being dosed.

Cardiac assessments (see Section 7.2.2.6 for details)

Edinburgh Claudication Questionnaire (see Section 7.2.2.7 for details)
All medications and significant non-drug therapies taken within 14 days prior to first dose 
must be recorded on the Concomitant Medication eCRF page and updated on a continuous 
basis if there are any new changes to the medications. Medications include physician 
prescribed and over-the-counter medications, as well as vitamins, herbal, and alternative 
therapies. Information to be collected on concomitant medications/significant non-drug 
therapies will include the following:

Medication/non-drug therapy trade name

Reason for medication

Start date and end date or continuing at time of examination

Dosage regimen
For those patients consenting to participate in the optional Stem cells ENESTPath substudy, a 
determination of Ph+ stem cells in bone marrow will be performed during the screening visit, 
before starting nilotinib 300 mg BID treatment.
7.1.3
Run-in-period
Not applicable.
7.1.4
Induction/consolidation phase
Patients in the induction/consolidation phase will undergo the following assessments on the 
first day of starting study treatment (Day 1 = study entry) and at every subsequent 3-month 
visit until the end of the consolidation phase (either 24 or 36 months, depending on eligibility 
and randomization arm):

Physical examination (see Section 7.2.2.1 for details)

Vital signs (see Section 7.2.2.2 for details)

ECOG performance status (see Section 7.2.2.3 for details)

Hematology (see Section 7.2.2.4.1 for details)

Clinical chemistry (see Section 7.2.2.4.2 for details)

Serum pregnancy test only at Day 1 (see Section 7.2.2.4.3)

Urine analysis only at Day 1 (see Section 7.2.2.4.4)

Serology (Hep B) if not done at an earlier visit (see Section 7.2.2.4.5 for details)
The patient may be required to attend optional visits at Day 15 and Month 1 based on local 
requirements or as clinically indicated.
In the event that Day 1 is performed within 8 days from the screening visit, the following 
evaluations should not be repeated on Day 1:

Physical examination (see Section 7.2.2.1 for details);


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
Vital signs (see Section 7.2.2.2 for details);

ECOG performance status (see Section 7.2.2.3 for details)

Hematology (see Section 7.2.2.4.1 for details)

Clinical chemistry (see Section 7.2.2.4.2 for details)

Serum pregnancy test (see Section 7.2.2.4.3 for details)

Urine analysis (see Section 7.2.2.4.4 for details)
Urine pregnancy tests will be performed monthly from Month 1 (see Section 7.2.2.4.3 for 
details).
Peripheral blood will be taken for BCR-ABL RQ-PCR assessment (performed in a EUTOS 
standardized laboratory) from Month 3 and at each subsequent 3-month visit until the end of 
the consolidation phase in order to assess the effectiveness of the study medication (see 
Section 7.2.1.1 for details).
An ECG will also be performed at Month 3 and at the End of Phase (EOP) visit (and at the 
optional visits of Day 15 and Month 1, if required) (see Section 7.2.2.6.1 for details).
Patients will complete an Edinburgh Claudication Questionnaire at 6-monthly intervals for the 
duration of the study (see Section 7.2.2.7 for details).
Bone marrow assessments/cytogenetics and mutational analysis will be performed if a patient 
demonstrates a loss of MMR or has not achieved MMR and it is deemed clinically indicated 
by the investigator. If the result is positive for a mutation, further analysis will be performed 
as needed at the discretion of the investigator (see Section 7.2.1.3 for details).
The recording of study drug dosing, concomitant medications, and assessment of AEs will be 
performed on a continuous basis throughout the initiation/consolidation phase.
A “visit window” of ± 7 days is allowed during the induction/consolidation phase.
For those patients consenting to participate in the optional Stem cells ENESTPath substudy, a 
determination of Ph+ stem cells in bone marrow will be performed after 24 months of 
nilotinib treatment (at Visit 8).
For those patients consenting to participate to the ‘CML patients voice’ Italian substudy, 
quiestionnaires and expressive writing assessemnts will be conducted at Visit 6 - Month 18. 
[Post Text Supplement 1].
7.1.5
Randomization/Eligibility visit
After completion of the Month 24 visit, the patient will continue nilotinib treatment until Visit 
9-Randomization, which should occur within 15 working days from the last visit.
If the patient has been in sustained ≥MR4.0 for the previous 12 months as evaluated and 
confirmed on Visit 9, randomization to one of the two treatment arms will be done by using 
an interactive voice response system (IVRS). Detailed instruction on the use of the IVRS will 
be given in a manual.


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Patients will be deemed to be in sustained molecular response if:

Four out of the preceding five quarterly RQ-PCR assessments were ≥MR4.0 (equal or more 
than MR4.0), and

The last assessment was ≥MR4.0 (equal or more than MR4.0).
If the patient is randomized to Arm 1, the study treatment will be immediately interrupted and 
the patient will be instructed to follow the schedule of the Arm 1 TFR phase.
At Visit 9 - Randomization, patients will be asked to return their remaining supply of study 
drug to site.
If the patient is randomized to Arm 2, the study treatment will continue for an additional 12 
months with the same visit schedule as in the first 2 year of consolidation treatment and study 
drug will be dispensed.
After completion of the Month 36 visit, the patient will continue nilotinib treatment until Visit 
205-Eligibility, which should occur within 15 working days from the last visit. If the patient is 
still eligible to enter the TFR phase, the patient will be instructed by the investigator to follow 
the visit schedule of the Arm 2 TFR phase.
At Visit 205 - Eligibility, patients will be asked to return any remaining supply of study drug.
For those patients consenting to participate in the optional Stem cells ENEST substudy, and 
randomized to Arm 2, a determination of Ph+ stem cells in bone marrow will be performed 
after 36 months of nilotinib treatment (Visit 204).
For those patients consenting to participate to the ‘CML patient’s voice’ Italian substudy, 
quiestionnaires and expressive writing assessemnts will be conducted at Visit 9 -
Randomization. [Post Text Supplement 1]
Patients not having confirmed sustained molecular response at 24 months (or at 36 months 
depending on eligibility for randomization) will exit the study and will be treated at the 
discretion of the investigator according to standard practice. Information on survival, stem cell 
transplant and the status of the patient’s disease (i.e. disease progression to AP/BC according 
to protocol definition, TKI treatment) will be collected until death, progression, or 5 years 
from study entry, whichever comes first.
For those patients consenting to participate to the ‘CML patient’s voice’ Italian substudy, 
quality of life quiestionnaires and in-depth qualitative interviews will be conducted at Visit 9 -
Randomization. [Post Text Supplement 1]
The following assessments will be performed at the Randomization-Eligibility visits:

Physical examination (see Section 7.2.2.1 for details);

Vital signs (see Section 7.2.2.2 for details);

Hematology (see Section 7.2.2.4.1 for details);

Clinical chemistry (see Section 7.2.2.4.2 for details);

Serology (Hep B) if not done at an earlier visit (see Section 7.2.2.4.5 for details);

Serum pregnancy test (if patient withdrawn from the study).
At this visit, no peripheral blood BCR-ABL RQ-PCR will be done.


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If the Randomization/Eligibility visit is done within 15 days from Visit 8 or Visit 204 
(depending on randomization arm), the above assessments should not be repeated, except for 
the serum pregnancy test.
7.1.6
Treatment-free remission phase
Following the cessation of study therapy (at either 24 or 36 months, depending on 
randomization), patients will attend visits at the following time frames:

Every month for the first 6 months of the TFR phase (both Arms)

Every 2 months between Months 8 and 12 of the TFR phase (both Arms)

Every 3 months between Months 15 and 24 of the TFR phase (both Arms)

Every 3 months between Months 27 and 36 of the TFR phase for patients enrolled into 
Arm 1 of the study
At the TFR Month 1 visit, patients will be asked to return their remaining supply of study 
drug to site if not done at Visit 9 - Randomization or Visit 205 - Eligibility depending on the 
randomization arm.
At each of the visit times stated above, peripheral blood will be taken for BCR-ABL RQ-PCR 
assessment (performed in a EUTOS standardized laboratory) and hematologic assessments 
(see Section 7.2.2.4.1 for details).
In addition, the following assessments will be performed at 6-month intervals:

Physical examination (see Section 7.2.2.1 for details)

Vital signs (see Section 7.2.2.2 for details)

ECOG performance status; clinical chemistry (see Section 7.2.2.4.2 for details)

ECG if needed (see Section 7.2.2.6.1)

Edinburgh Claudication Questionnaire (see Section 7.2.2.7 for details)

Clinical chemistry (see Section 7.2.2.4.2 for details);
A urine pregnancy test will also be performed monthly, and test results will be documented in 
a diary by the patient (see Section 7.2.2.4.3);
Bone marrow assessments/cytogenetics and mutational analysis will be performed if a patient 
demonstrates a loss of MMR. If the result is positive for a mutation, further analysis will be 
performed as needed at the discretion of the investigator.
Patients who need to re-start the treatment with Nilotinib due to a relapse in the TFR phase 
need to be assessed for Hepatitis B if not done at an earlier visit to identify chronic carriers of 
the virus (see Section 7.2.2.4.5 for details).
For those patients consenting to participate to the ‘CML patient’s voice’ Italian substudy, 
quality of life quiestionnaires and in-depth qualitative interviews will be conducted in this 
phase. [Post Text Supplement 1]
The recording of concomitant medications and assessment of AEs will be performed on a 
continuous basis throughout the TFR phase.
A “visit window” of ± 7 days is allowed during the TFR phase.


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7.1.7
Nilotinib re-treatment phase (if applicable)
If according to the EUTOS standardized laboratory result, the definition of relapse (loss of 
MMR/confirmed loss of MR4.0) is met, the investigator should contact the patient for 
immediate start of the nilotinib re-treatment phase. Treatment with nilotinib should re-start at 
the same dose taken before the TFR phase (i.e., the re-treatment dose will be nilotinib 300 mg 
BID or a lower dose of nilotinib if the dose was reduced in the consolidation phase 
before entering the TFR phase).
The following assessments should be performed on Day 1 of the re-treatment phase if not 
already performed on the day of confirmed loss of MR4.0, or loss of MMR:

Physical examination (see Section 7.2.2.1 for details)

Vital signs (see Section 7.2.2.2 for details)

ECOG performance status (see Section 7.2.2.4.2 for details)

ECG (see Section 7.2.2.6.1 for details)

Hematology (see Section 7.2.2.4.1 for details)

Clinical chemistry (see Section 7.2.2.4.2 for details)

Serum pregnancy test (see Section 7.2.2.4.3 for details)

Serology (Hep B) if not done at an earlier visit (see Section 7.2.2.4.5 for details)

Edinburgh Claudication Questionnaire (see Section 7.2.2.7 for details)
Peripheral blood for BCR ABL RQ PCR (done in a EUTOS standardized laboratory) and 
mutational analysis should not be repeated On Day 1 of the re-treatment phase.
Subsequently, patients will attend study visits every 3 months until they complete 5 years 
from study entry, and will undergo the assessments as per Table 7-4:
Bone marrow assessments/cytogenetics and mutational analysis will be performed if a patient 
demonstrates a loss of MMR. If the result is positive for a mutation, further analysis will be 
performed as needed at the discretion of the investigator.
Patients will complete an Edinburgh Claudication Questionnaire at 6-month intervals for the 
duration of the study (see Section 7.2.2.7 for details).
A “visit window” of ± 7 days is allowed during the re-treatment phase.
The recording of study drug dosing, concomitant medications and assessment of AEs will be 
performed on a continuous basis throughout the re-treatment phase.
7.1.8
End of Phase visit, including premature withdrawal and study 
discontinuation visit
Patients will attend the following EOP visits depending on the time points they will interrupt 
the study:

Visit 400: end of induction/consolidation phase if the patient withdraws at any time from 
baseline to Visit 8 for Arm 1 or to Visit 204 for Arm 2 or if the patient does not achieve
stable ≥MR4.0 during the second year of the induction/consolidation phase


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
Visit 401: end of the TFR phase if the patient withdraws during the TFR phase at any time
from Visit 101 to Visit 117 for Arm 1 or from Visit 206 to Visit 218 for Arm 2 and patient 
doesn’t start re-treatment phase

Visit 402: end of re-treatment phase for patients withdrawn from the nilotinib re-treatment 
phase at any time from Visit 301 to Visit 314
The following assessments will be performed at the above-mentioned EOP visits:

Physical examination (see Section 7.2.2.1 for details)

Vital signs (see Section 7.2.2.2 for details)

ECOG performance status (see Section 7.2.2.4.2 for details)

ECG (see Section 7.2.2.6.1 for details)

Hematology (see Section 7.2.2.4.1 for details)

Clinical chemistry (see Section 7.2.2.4.2 for details)

Serology (Hep B) if not done at an earlier visit (see Section 7.2.2.4.5 for details)

Peripheral blood BCR-ABL RQ-PCR

Serum pregnancy test (if patient is withdrawn from the study)
The recording of concomitant medications and assessment of AEs will also be performed.
An EOP eCRF page should be completed, giving the date and reason for stopping the study 
period prematurely (if applicable).
If a patient refuses to return for the EOP visit or is unable to do so, every effort should be 
made to contact them or a knowledgeable informant by telephone to obtain information. The 
investigator should show “due diligence” by documenting in the source documents the steps 
taken to contact the patient, e.g. dates of telephone calls, registered letters, etc. An EOP eCRF 
page should be completed.
All patients who discontinue the study (whether due to successful completion of any of the 
study phases, or premature withdrawal) should be contacted for safety evaluations 30 days 
from the EOP visit in order to follow any safety issues and record/update concomitant 
medications. This information may be collected by a telephone call or a clinic visit, if 
conducted by a telephone call this may trigger a safety follow-up visit if a medical 
intervention is necessary.
For patients returning to the site for a safety follow-up visit a Hepatitis B testing will be 
performed once if not performed at an earlier visit to identify chronic carriers of the virus (see 
Section 7.2.2.4.5 for details). The patient should then be informed about the outcome of the 
serology test and the potential risk for Hepatitis B reactivation if the test result was positive.
For patients who discontinue earlier in any phase and don’t accept to be followed for survival, 
an EOS eCRF page should be completed.
For patients who accept to be followed for survival see Section 7.1.9.


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7.1.8.1
Criteria for premature patient withdrawal
Patients may voluntarily withdraw from the study or be dropped from it at the discretion of 
the investigator at any time. Patients may be withdrawn from the study if any of the following 
occur:

AEs

Abnormal laboratory value(s), if deemed necessary by the investigator

Abnormal test procedure result(s), if deemed necessary by the investigator

Pregnancy (patients must be withdrawn if pregnancy occurs during the nilotinib 
induction/consolidation phase or the nilotinib re-treatment phase. In case of a pregnancy 
during the TFR phase, the pregnant woman can stay in the TFR phase as long as no 
nilotinib treatment is needed, but she must be withdrawn from the study when/if she meets 
the definition of relapse [loss of MMR/confirmed loss of MR4.0])

Protocol violation

Subject withdrew consent

Lost to follow-up

Administrative issues

Death
In addition, patients should be withdrawn from the study in the event of disease progression, 
defined as:

Progression to CML-AP, i.e.:

≥ 15% blasts in peripheral blood or bone marrow aspirate, but < 30% blasts in both 
peripheral blood and bone marrow aspirate

≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow aspirate

≥ 20% basophils in peripheral blood

Thrombocytopenia (< 100 x 109/L) that is unrelated to therapy

Progression to BC, as defined by any of the following:

≥30% blasts in peripheral blood or bone marrow aspirate

Appearance of extramedullary involvement other than hepato- and/or splenomegaly 
proven by biopsy (i.e. chloroma)
7.1.9
Follow-up period
Patients who terminate the study early in any phase for any reason and accept to be followed
(see Section 7.1.8.1 for details) will be contacted every 3 months ± 21 days until 5 years from 
study entry. Information on survival, stem cell transplant, and the status of the patient’s 
disease (i.e. disease progression to AP/BC according to protocol definition, TKI treatment) 
will be collected. Patients lost to follow-up during this time should be recorded as such on the 
eCRF. For patients who are lost to follow-up, the investigator should show “due diligence” by 
documenting in the source documents the steps taken to contact the patient, e.g., dates of 
telephone calls, registered letters, etc.


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The EOS page should be completed when the patient completes/interrupts the follow-up
period.
7.2
Assessment types
7.2.1
Efficacy assessments
Efficacy assessments will be performed at the time points indicated Table 7-1, Table 7-2, and 
Table 7-3.
7.2.1.1
Molecular response
Molecular response will be assessed in all patients. Levels of BCR-ABL transcripts will be 
determined by RQ-PCR testing of peripheral blood and analyzed at a EUTOS standardized 
laboratory according to the methodology described in the EUTOS guidelines (version 
published in Feb 2015).
The percent ratio of BCR-ABL transcripts versus control gene transcripts converted to IS will 
be calculated for each sample.
If a suitable peripheral blood sample for RQ-PCR testing was not obtained during the normal 
visit schedule, then a subsequent sample must be collected at an unscheduled visit within 
4 weeks. Examples for deeming a sample unsuitable include:

A sample becoming lost during transit to the PCR laboratory in the consolidation/TFR and 
re-treatment phases

Insufficient sample quality (degraded/insufficient RNA)
Molecular response and related variables are defined as the following (see detailed definition 
in Glossary of terms):

MMR (MR3.0): BCR-ABL ≤ 0.1% (IS)

MR4.0: BCR-ABL ≤ 0.01% (IS)

MR4.5: BCR-ABL ≤0.0032% (IS)

MR 5 : BCR-ABL ≤0.001% (IS)
7.2.1.2
Mutational analysis
Mutational analysis will be performed at a EUTOS standardized laboratories.
During the study, in a patient with loss of MMR, mutational analyses will be performed on the 
cDNA available from the RQ-PCR at this time point. Continued mutational analyses may be 
performed as clinically indicated.
Sites will use standard materials for sample collection and shipment. Collection, storage, and 
shipment of samples for mutational analysis will follow the standard practice of the 
designated EUTOS standardized laboratory, as described in the Study Site Laboratory Manual. 
Samples will be refrigerated (2oC to 8oC) after preparation, and shipped to the designated 
EUTOS standardized laboratory at room temperature as described in the [Laboratory Manual].


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7.2.1.3
Bone marrow analysis and cytogenetics
If a patient is deemed to be in less than MMR, as assessed by a EUTOS standardized 
laboratory, CgR assessment must be performed as soon as possible. Cytogenetics must be 
performed by chromosome banding analysis (CBA) of marrow cell metaphases. If marrow 
cells cannot be obtained, CBA can be substituted with interphase FISH of blood cells, using 
dual color dual fusion probes that allow the detection of BCRABL+ nuclei. However, based 
on interphase FISH, one cannot assess the degree of CgR, (minimal, minor, partial) but can 
establish only if the CgR is complete (< 1% BCR-ABL+ nuclei out of at least 200 nuclei).
Bone marrow assessments/cytogenetics will be performed if a patient demonstrates a loss of 
MMR during the study.
Cytogenetic response will be assessed as the percentage of Ph+ metaphases in the bone 
marrow and is defined as the following (a review of a minimum of 20 metaphases is 
required):

Complete (CCyR): 0% Ph+ metaphases

Partial (PCyR): > 0% to 35% Ph+ metaphases

Major (MCyR): 0% to 35% Ph+ metaphases

Minor (mCyR): > 35% to 65% Ph+ metaphases

Minimal: > 65% to 95% Ph+ metaphases

None: > 95% to 100% Ph+ metaphases
A minimum of 20 metaphases must be examined in each bone marrow sample. Quantification 
of the percentage of Ph+ chromosome metaphases, number of metaphases, number positive 
for the Ph chromosome, additional chromosomal abnormalities as well as data from cytologic 
evaluation (microscopic analysis) of percentage of blasts and promyelocytes will be recorded 
on the Bone Marrow eCRF. These examinations will be performed and analyzed locally.
7.2.2
Safety and tolerability assessments
Safety and tolerability assessments will be performed at the time points indicated in Table 7-1, 
Table 7-2, and Table 7-3.
Safety will be monitored by performing the assessments described below, in addition to 
collecting AE data at every visit. For details on AE collection and reporting, please refer to 
Section 8.
Significant findings that were present prior to the signing of informed consent must be 
included in the Relevant Medical History/Current Medical Conditions page on the patient’s 
eCRF. Significant new findings that begin or worsen after signing of informed consent must 
be recorded on the AE page of the patient’s eCRF.


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7.2.2.1
Physical examination
Physical examination will include an assessment of height (measured in cm at screening only), 
body weight (to the nearest 0.1 kilogram [kg] in indoor clothing, but without shoes) and an 
examination of the general appearance of the patient, including skin, neck (including thyroid), 
eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular, and 
neurological.
Patients are encouraged to measure their body weight regularly and to report to the study 
investigator any body-weight change of more than 2 kg as compared to their pre-study body 
weight to detect early signs of fluid retention. Rapid weight gain of ≥ 2 kg should be carefully 
investigated and other measures considered as appropriate.
Information about the physical examination must be present in the source documentation at 
the study site.
Significant findings that were present prior to the signing of informed consent must be 
included in the Relevant Medical History/Current Medical Conditions page on the patient’s 
eCRF. Significant new findings that begin or worsen after signing of informed consent must 
be recorded on the AE page of the patient’s eCRF.
Presence of extramedullary leukemic involvement will be checked at each physical 
examination as outlined above. Findings on physical examination consistent with 
extramedullary leukemic involvement will be recorded (e.g. lymph nodes, liver, and spleen 
size). With regards to lymph nodes, palpable lymph nodes should be considered to be CML 
related only if leukemic blast infiltration has been confirmed via biopsy/histology or by
technically adequate (not contaminated with peripheral blood) aspiration cytology.
When extramedullary involvement other than of the spleen or liver is the only evidence of 
blast crisis, this finding must be confirmed by technically adequate (not contaminated with 
peripheral blood) aspiration cytology and /or biopsy (especially for isolated lymph nodes) and
data entered into the extramedullary involvement eCRF.
7.2.2.2
Vital signs
Vital signs (blood pressure, heart rate, and body temperature) will be assessed with the patient 
in the sitting position after 2 minutes of rest. Body temperature may be measured orally or via 
ear.
7.2.2.3
Performance status
The patient’s performance status will be assessed according to the ECOG performance status 
scale (see Table 7-5).


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Table 7-5
ECOG performance criteria
ECOG Grade
Status
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, e.g. light house work, office work
2
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about 
more than 50% of waking hours
3
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5
Dead
Source: Oken MM, Creech RH, Tormey DC, et al (1982). Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol; 5:649-55. 
7.2.2.4
Laboratory evaluations
The laboratory evaluations will be performed by a local laboratory. Novartis must be provided 
with a copy of the certification and tabulation of the normal ranges for all local laboratories 
used.
Abnormal laboratory values or test results constitute an AE only if they induce clinical signs 
or symptoms, and are considered clinically significant (i.e. requires dose modification and/or 
interruption of study drug, leads to clinical symptoms, causes study discontinuation, or itself 
constitutes a SAE) or require therapy. These events should be recorded on the AE eCRF, as 
well as the appropriate laboratory eCRF and/or comment eCRF page. If the administration of 
nilotinib is delayed/modified due to unacceptable toxicities (see Section 6.3), re-evaluation 
should be performed prior to the next study treatment at a minimum.
All available laboratory evaluations should be performed and results reviewed prior to 
administration of study drug. More frequent examinations may be performed at the 
investigator’s discretion if medically indicated; results should be recorded on the Unscheduled 
Visit eCRF.
7.2.2.4.1 Hematology
Hematology includes assessment of hemoglobin, platelet count, total (absolute) white blood 
cell (WBC) count and an automated and/or manual full differential count, including absolute 
values and percentages of neutrophils, lymphocytes, eosinophils, basophils, monocytes,
promyelocytes, myelocytes, meta myelocytes, and blast cells.
7.2.2.4.2 Clinical chemistry
Clinical chemistry tests will include AST (SGOT), ALT (SGPT), direct bilirubin, indirect 
bilirubin, total bilirubin, alkaline
phosphatase, lipase, amylase
(optional), lactate 
dehydrogenase (LDH), albumin, triglycerides, high-density lipoprotein (HDL), low density 
lipoprotein (LDL), total cholesterol, fasting glucose, serum creatinine, potassium, magnesium, 
calcium, inorganic phosphorus, and sodium. Potassium, calcium, magnesium, and/or sodium 
supplements may be given to correct values that are < LLN. Post-correction values must not 
be deemed to be a clinically significant abnormality prior to patients being dosed.


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HDL, LDL, total cholesterol, and triglycerides should be assessed under fasting conditions. 
Thus, those parameters in addition to the evaluation of fasting glucose may be conducted in 
the external laboratory within 7 days prior to scheduled visits. If HDL, LDL, total cholesterol,
and triglycerides assessments are not performed under fasting conditions, an unscheduled 
assessment should be performed within 15 days in order to collect these parameters under 
fasting conditions. If the assessment of fasting glucose was not performed at either the 
external laboratory or at site visit, the HbA1C assessment will replace the missing fasting 
glucose test, but every effort should be made to collect the fasting glucose result.
HbA1C will be included in the clinical chemistry assessment for every patient during the 
duration of the trial (screening, every 3 months while under nilotinib treatment, and every 
6 months during the TFR phase).
7.2.2.4.3 Pregnancy assessment
All women of childbearing potential (WOCBP) should undergo serum and urine pregnancy 
testing at the time points stated in Table 7-1, Table 7-2, Table 7-3, and Table 7-4.
Urine pregnancy testing will be performed by the patient on a monthly basis during the 
induction/consolidation phase, the TFR phase, and the re-treatment phase. The results of these 
tests should be recorded in the patient diary, which should be shown to the investigator at 
each visit to confirm that any WOCBP is not pregnant. If a test result indicates a pregnancy, 
the patient must contact the investigator immediately.
If a patient becomes pregnant or suspects being pregnant during the study or within 30 days
after last dose of nilotinib, the Study Doctor needs to be informed immediately, and study 
treatment with nilotinib must be stopped immediately.
Pregnancy testing is not required for patients who are determined to be post-menopausal.
Women are considered post-menopausal and not of childbearing potential if they have had 
12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age 
appropriate) or have had surgical bilateral oophorectomy with or without hysterectomy or 
tubal ligation at least 6 weeks prior to enrolling. In the case of oophorectomy alone, only 
when the reproductive status of the woman has been confirmed by follow-up hormone level 
assessment is she considered to be not of childbearing potential.
7.2.2.4.4 Urine analysis
At the screening and Baseline visits, a urine test will be performed to assess the presence of 
microalbuminuria in patients with known diabetes mellitus.
7.2.2.4.5 Serology (Hepatitis B testing)
Patients will be tested once for the following hepatitis B serologic markers: hepatitis B surface 
antigen (HBs Ag) and antibodies to hepatitis B core antigen (HBc Ab / anti HBc).
Patients currently on nilotinib in the induction and consolidation phases of the study should 
have testing performed at the next possible visit in order to identify chronic carriers.
Patients in the TFR phases of the study should be tested for hepatitis B virus before re-
initiating treatment with nilotinib.


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7.2.2.5
Radiological examinations
No radiological examinations will be performed for the assessment of safety.
7.2.2.6
Cardiac assessments
7.2.2.6.1 Electrocardiogram
A 12-lead ECG should be obtained at screening and at the time points indicated in Table 7-1, 
Table 7-2, Table 7-3, and Table 7-4.
Interpretation of the standard 12-lead ECG tracing must be made by a qualified physician and 
documented on the ECG eCRF page. QTc will be calculated according to Fridericia’s formula. 
Each ECG tracing should be labeled with the study number, patient initials (where regulations 
permit), patient number and date, and kept in the source documents at the study site. 
Clinically significant abnormalities present when the patient signed informed consent should 
be reported on the Medical History eCRF page. New or worsened clinically significant 
findings occurring after informed consent must be recorded on the Adverse Events eCRF page.
At Day 1 of nilotinib re-treatment, QTcF must be < 450 msec prior to re-starting nilotinib. For 
patients with QTcF prolongation above 450 msec, an analysis of serum potassium and 
magnesium should be performed, and if below normal, corrected with supplements to within 
normal limits. Concomitant medications must be reviewed for their potential to inhibit 
CYP3A4 and/or to prolong QT interval. A repeat ECG should be performed within 1 hour of 
the first QTcF of > 450 msec. If QTcF remains > 450 msec, then repeat ECG as clinically 
indicated, but at least once a day until the QTcF returns to < 450 msec.
In case of a grade 3 QT interval prolongation, a cardiologist’s opinion should be requested,
and an appropriate and closer cardiac monitoring of the patient must be put in place until the 
QTcF decreases to < 500 msec.
Additional ECGs can be performed at any time at the investigator’s discretion.
7.2.2.6.2 Echocardiogram
Echocardiography will be performed at screening to assess left ventricular ejection fraction
and may be repeated at the investigator’s discretion if there are signs or symptoms of 
cardiotoxicity.
7.2.2.7
Edinburgh Claudication Questionnaire
Patients will complete an Edinburgh Claudication Questionnaire at screening and at 6-month 
intervals thereafter for the duration of the study (provided in Appendix 14.2).
The questionnaire will be used to see whether it may predict a higher chance of developing 
PAOD/ICVE in patients treated with nilotinib. The rate of specific AEs of interest will be 
calculated in the two groups of patients with either positive or negative tests. The test however 
will not be used as a selection criterion to include or exclude patients.
In case the questionnaire results positive at any visits, please refer to a cardiovascular expert 
for further assessments.




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Adverse events that begin or worsen after informed consent should be recorded in the Adverse 
Events eCRF. Conditions that were already present at the time informed consent was signed 
should be recorded in the Medical History eCRF. Adverse event monitoring should be 
continued during TFR phase, and for at least 30 days following the last dose of study 
treatment or the last day of the TFR phase. Adverse events (including laboratory
abnormalities that constitute AEs) should be described using a diagnosis whenever possible, 
rather than individual underlying signs and symptoms. When a clear diagnosis cannot be 
identified, each sign or symptom should be reported as a separate AE.
Adverse events will be assessed according to the Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.03. If CTCAE grading does not exist for an AE, the severity of 
mild, moderate, severe, and life-threatening, corresponding to grades 1 to 4, will be used. 
CTCAE grade 5 (death) will not be used in this study; rather, information about deaths will be 
collected though a Death form.
The occurrence of AEs should be sought by non-directive questioning of the patient during 
the screening process after signing informed consent and at each visit during the study. 
Adverse events also may be detected when they are volunteered by the patient during the 
screening process or between visits, or through physical examination, laboratory test, or other 
assessments. As far as possible, each AE should be evaluated to determine:

The severity grade (CTCAE grade 1-4)

Its duration (start and end dates)

Its relationship to the study treatment (reasonable possibility that AE is related: No, Yes)

Action taken with respect to study or investigational treatment (none, dose adjusted, 
temporarily interrupted, permanently discontinued, unknown, not applicable)

Whether medication or therapy taken (no concomitant medication/non-drug therapy, 
concomitant medication/non-drug therapy)

Outcome (not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequalae, fatal, unknown)

Whether it is serious, where a SAE is defined as in Section 8.2.1
All AEs should be treated appropriately. If a concomitant medication or non-drug therapy is 
given, this action should be recorded on the Adverse Event eCRF.
Once an AE is detected, it should be followed until its resolution or until it is judged to be 
permanent, and assessment should be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to the study treatment, the interventions 
required to treat it, and the outcome.
Natural progression or deterioration of the malignancy under treatment (including loss of 
response, progression to AP/BC, and death due to disease progression) will be recorded as 
part of the efficacy evaluation and should not be reported as an AE/SAE.
AEs separate from the progression of malignancy (e.g. deep vein thrombosis at the time of 
progression or hemoptysis concurrent with finding of disease progression) will be reported as 
per usual guidelines used for such events with proper attribution regarding relatedness to the 
drug.


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8.1.2
Laboratory test abnormalities
8.1.2.1
Definitions and reporting
Laboratory abnormalities that constitute an AE in their own right (i.e. are considered 
clinically significant, induce clinical signs or symptoms, require concomitant therapy, or 
require changes in study treatment) should be recorded on the Adverse Events eCRF. 
Whenever possible, a diagnosis, rather than a symptom should be provided (e.g. anemia 
instead of low hemoglobin). Laboratory abnormalities that meet the criteria for an AE should 
be followed until they have returned to normal or an adequate explanation of the abnormality 
is found. When an abnormal laboratory or test result corresponds to a sign/symptom of an 
already reported AE, it is not necessary to separately record the laboratory/test result as an 
additional event.
Laboratory abnormalities that do not meet the definition of an AE should not be reported as 
AEs. A grade 3 or 4 event (severe) as per CTCAE does not automatically indicate a SAE 
unless it meets the definition of serious as defined below and/or as per investigator’s 
discretion. A dose hold or medication for the laboratory abnormality may be required by the 
protocol, in which case the laboratory abnormality should still be reported as an AE.
8.1.3
Adverse events of special interest
Ischemic vascular and ischemic cardiovascular events include (but are not limited to) the 
events listed below. Patients should be educated on the clinical symptoms of such events to 
ensure accurate reporting to the investigator.

Ischemic Heart Disease (IHD: angina pectoris, coronary artery disease, acute myocardial 
infarction, and coronary artery stenosis

Ischemic Cerebrovascular Events (ICVE: ischemic cerebrovascular accident and transient 
ischemic attack

Peripheral Artery Occlusive Disease (PAOD: intermittent claudication and arterial 
stenosis of a limb
If patients experience ischemic vascular or ischemic cardiovascular events (i.e. ischemic, 
cardiac, cerebrovascular, or peripheral artery-related), carefully consider protocol guidance 
for dose reduction or study drug discontinuation (Protocol Table 6-2).
The investigator should ensure that the patient is assessed by a vascular or cardiovascular 
specialist. It is recommended that the standard of care for concurrent ischemic vascular or 
cardiovascular events should be given to the patients while they are receiving nilotinib 
therapy. All patients should have their risk factors for such diseases appropriately managed 
and follow the current recommendations. Careful consideration should be given to the 
recommendations outlined in the study protocol (Table 6-2, Table 6-3). Additional laboratory
assessments of lipid profile and glucose should be performed where clinically indicated.
The SSMC and DMC will be informed on regular basis on the grade 2-4 ischemic vascular or 
cardiovascular events occurring to the patients enrolled in the AMN107AIC05 trial.


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8.2
Serious adverse events
8.2.1
Definitions
A SAE is defined as one of the following:

Is fatal or life-threatening

Results in persistent or significant disability/incapacity

Constitutes a congenital anomaly/birth defect

Is medically significant, i.e. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention to prevent one of the outcomes listed above

Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:

Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition (specify what this includes)

Elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent

Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission

Social reasons and respite care in the absence of any deterioration in the patient’s 
general condition
Protocol-exempt SAEs are SAEs specifically defined in the protocol where there has been a 
clear agreement with regulators not to collect these SAEs in the safety database, provided the 
information is collected elsewhere. For example, this may include SAEs that are also a 
primary outcome measure, such as mortality, survival rate, or number of flares of the 
condition being studied.
8.2.2
Reporting
To ensure patient safety, every SAE, regardless of suspected causality, occurring after the 
patient has provided informed consent and until at least 30 days after the patient has ended the
study (EOS) must be reported to Novartis within 24 hours of learning of its occurrence. Any 
SAEs experienced after this 30-day period (or five half-lives, whichever is longer) should 
only be reported to Novartis if the investigator suspects a causal relationship to the study 
treatment. Recurrent episodes, complications, or progression of the initial SAE must be 
reported as follow-up to the original episode within 24 hours of the investigator receiving the 
follow-up information. An SAE occurring at a different time interval or that is otherwise 
considered completely unrelated to a previously reported one should be reported separately as 
a new event.
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form. The investigator must assess and record the relationship of each SAE to each specific 
study treatment (if there is more than one study treatment), complete the SAE Report Form in 
English, and send the completed, signed form by fax within 24 hours to the oncology Novartis 
Drug Safety and Epidemiology (DS&E) department.


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The telephone and telefax number of the contact persons in the local department of DS&E, 
specific to the site, are listed in the investigator folder provided to each site. The original copy 
of the SAE Report Form and the fax confirmation sheet must be kept with the eCRF 
documentation at the study site.
Follow-up information is sent to the same contact(s) to whom the original SAE Report Form 
was sent, using a new SAE Report Form stating that this is a follow-up to the previously 
reported SAE and giving the date of the original report. Each reoccurrence, complication, or 
progression of the original event should be reported as a follow-up to that event regardless of 
when it occurs. The follow-up information should describe whether the event has resolved or 
continues, if and how it was treated, and whether the patient continued or withdrew from 
study participation.
8.3
Emergency unblinding of treatment assignment
Not applicable.
8.4
Pregnancies
To ensure patient safety, each pregnancy in a patient in the induction/consolidation phase, the 
TFR phase, or the re-treatment phase, or within 30 days of the last dose of nilotinib, must be 
reported to Novartis within 24 hours of learning about it. The pregnancy should be followed 
up to determine outcome, including spontaneous or voluntary termination, details of the birth, 
and the presence or absence of any birth defects, congenital abnormalities, or maternal and/or 
newborn complications. If a study patient becomes pregnant or suspects being pregnant 
during the study or within 30 days of the last dose of nilotinib, the Study Doctor needs to be 
informed immediately, and study treatment with nilotinib has to be stopped immediately.
Pregnancy should be recorded on a Clinical Study Pregnancy Form and reported by the 
investigator to the oncology Novartis DS&E department. Pregnancy follow-up should be 
recorded on the same form and should include an assessment of the possible relationship of 
any pregnancy outcome to the Novartis study treatment. Any SAE experienced during 
pregnancy must be reported on the SAE Report Form.
8.5
Warnings and precautions
No evidence available at the time of the approval of this study protocol indicated that special 
warnings or precautions were appropriate, other than those noted in the provided [Investigator 
Brochure]. Additional safety information collected between IB updates will be communicated 
in the form of Investigator Notifications. This information will be included in the patient ICF
and should be discussed with the patient during the study as needed.
8.6
Data Monitoring Committee (DMC)
A Data Monitoring Committee (DMC) will be established prior to the randomization of the 
first patient. The DMC will be responsible for reviewing the trial. It is expected that the DMC
will consist of four hematologists, one cardiologist, and one PAG member. There will be a 
DMC charter describing their roles and responsibilities and discussing potential data format
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DMC reports will be provided regularly and specifically:

When at least 200 patients enrolled in the trial have been treated with nilotinib 300 mg
BID for 6 months or discontinued earlier

When 300 patients have been treated for 1 year (expected in March 2015), with objectives 
to assess both efficacy and safety.

When 300 patients have been treated for 2 years (expected in March 2016) with the 
objectives to assess both efficacy and safety.

After 100 patients have had a minimum of 6 months’ follow-up in the TFR phase
DMC reports will include a first assessment of molecular response and early discontinuation 
rate after switching treatment to nilotinib. If the response rates or the attrition rate makes the 
achievement of the target number of patients randomized unlikely, the overall number of 
patients needing to be enrolled into the trial will be reassessed in coordination with the study 
statistician.
In addition to the planned DMC reports, additional safety analyses may also be performed at 
the discretion of the DMC.
The above timing for meetings will be discussed with the DMC and modified if requested 
during the course of the trial.
It is envisioned that the DMC may make four types of recommendations, namely:
1. No safety issues, ethical to continue the study as planned
2. Recommendation to continue the study but proposing an amendment to the protocol (e.g. 
incorporate additional safety assessments)
3. Serious safety concerns precluding further study conduct, regardless of efficacy
4. Other recommendations per DMC decision
8.7
Scientific Study Management Committee
An SSMC will be established comprising investigators participating in the trial who are 
clinical experts in CML.
The SSMC will ensure:

Transparent management of the study according to the protocol through recommending 
and approving modifications as circumstances require

Review of protocol amendments as appropriate
At a minimum, the SSMC will meet once a year. The details of the role of the SSMC are 
defined in the SSMC charter.
9
Data collection and management
9.1
Data confidentiality
Information about study patients will be kept confidential and managed under the applicable 
laws and regulations. Those regulations require a signed patient authorization informing the 
subject of the following:


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
What protected health information (PHI) will be collected from subjects in this study

Who will have access to that information and why

Who will use or disclose that information

The rights of a research subject to revoke their authorization for use of their PHI
In the event that a patient revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of patient 
authorization. For patients who have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (i.e. whether the patient is 
alive) at the end of their scheduled study period.
The data collection system for this study uses built-in security features to encrypt all data for 
transmission in both directions, preventing unauthorized access to confidential participant 
information. Access to the system will be controlled by a sequence of individually assigned 
user identification codes and passwords, made available only to authorized personnel who 
have completed prerequisite training.
Prior to entering key sensitive personally identifiable information (patient initials and exact 
date of birth), the system will prompt the site to verify that this data is allowed to be collected. 
If the site indicates that country rules or ethics committee standards do not permit collection 
of these items, the system will not solicit patient initials. Year of birth will be solicited (in the 
place of exact date of birth) to establish that the patient satisfies protocol age requirements 
and to enable appropriate age-related normal ranges to be used in assessing laboratory test 
results.
9.2
Site monitoring
Before study initiation, at a site initiation visit or at an investigator’s meeting, Novartis 
personnel (or designated Contract Research Organization [CRO]) will review the protocol and 
eCRFs with the investigators and their staff. During the study, the field monitor will visit the 
site regularly to check the completeness of patient records, the accuracy of entries on the 
eCRFs, the adherence to the protocol and to Good Clinical Practice (GCP), the progress of 
enrollment, and to ensure that study treatment is being stored, dispensed, and accounted for 
according to specifications. Key study personnel must be available to assist the field monitor 
during these visits.
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, ECGs, and the results of any other tests or assessments. All 
information recorded on eCRFs must be traceable to source documents in the patient’s file. 
The investigator must also keep the original signed ICF (a signed copy is given to the patient).
The investigator must give the field monitor access to all relevant source documents to 
confirm their consistency with the eCRF entries. Novartis monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
and documentation of SAEs. Additional checks of the consistency of the source data with the 
eCRFs are performed according to the study-specific monitoring plan.


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9.3
Data collection
This study will use Electronic Data Capture (EDC). The designated investigator staff will 
enter the data required by the protocol into the eCRF. The eCRFs have been built using fully 
validated secure web-enabled software that conforms to 21 CFR Part 11 requirements, 
investigator site staff will not be given access to the EDC system until they have been trained. 
Automatic validation programs check for data discrepancies in the eCRFs and allow 
modification or verification of the entered data by the investigator staff.
The Principal Investigator is responsible for assuring that the data entered into eCRF is 
complete and accurate, and that entry and updates are performed in a timely manner.
9.4
Database management and quality control
Novartis personnel (or designated CRO) will review the data entered by investigational staff 
for completeness and accuracy. Electronic data queries stating the nature of the problem and 
requesting clarification will be created for discrepancies and missing values and sent to the 
investigational site via the remote data capture (RDC) system. Designated investigator site 
staff are required to respond promptly to queries and to make any necessary changes to the 
data.
Concomitant treatments entered into the database will be coded using the World Health 
Organization Drug Reference List, which employs the Anatomical Therapeutic Chemical 
classification system. Medical history/current medical conditions and AEs will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA) terminology.
Randomization codes and data about which arm the patient has been assigned to will be 
tracked using IVRS. The data will be sent electronically to Novartis personnel (or designated 
CRO).
For RDC studies, after database lock, the investigator will receive a CD-ROM or paper copies 
of the patient data for archiving at the investigational site.
10
Statistical methods and data analysis
10.1
Analysis sets
10.1.1
Full Analysis Set
The Full Analysis Set (FAS) comprises all patients who complete the consolidation phase 
successfully (i.e. who maintain sustained MR4.0 or better (≥MR4.0) for the last 12 months on 
study) and are randomized.
10.1.2
Patients entering the TFR phase
This population includes all patients who are randomized and enter the TFR phase. For Arm 1,
this population matches the FAS. For Arm 2, it includes all patients entering the TFR phase 
after the additional 12-month treatment period.


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10.1.3
Safety Set
The Safety Set (SS) includes all patients who received at least one dose of study medication. 
Reporting of safety information for these patients will be split into subsets by study phases 
and corresponding time windows.
10.1.4
Per-Protocol Set
The PPS consists of a subset of the patients in the FAS who are compliant with requirements 
of the clinical study protocol.
Protocol deviations leading to exclusion from the PPS will be detailed in the report and 
analysis plan (RAP) and the validation and planning (VAP).
10.1.5
Other analysis sets
Secondary 
 efficacy analyses will be performed in the following analysis 
populations:

All patients enrolled who received at least one dose of study medication;

Patients entering the optional Stem cells substudy who received at least one dose of 
study medication.

Patients entering the ‘CML patient’s voice’ Italian substudy
10.2
Patient demographics/other screening characteristics
Demographic and other data will be summarized descriptively for both the SS and the FAS.
Categorical data will be presented as frequencies and percentages. For continuous data, 
summary statistics, such as mean, standard deviation, median, 25th and 75th percentiles, 
minimum, and maximum, will be presented.
10.3
Treatments (study treatment, concomitant therapies, compliance)
All study medication data will be summarized using the safety set (SS).
Time on treatment, duration of exposure, percentage of days on treatment, average dose 
intensity, and actual daily dose will be summarized.
Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be summarized.
10.4
Primary objective
The primary objective of this trial is to assess the optimal duration of consolidation treatment 
with nilotinib 300 mg BID in order that patients remain in TFR (≥MR4.0) without molecular 
relapse 12 months after entering the TFR phase.
10.4.1
Variable
The primary efficacy variable is the number of patients who remain in TFR (≥MR4.0), without 
molecular relapse and without re-starting nilotinib therapy, at the end of 12 months in the TFR 
phase of the study, in the nilotinib 12 months consolidation treatment arm (total trial time 24 


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months + 36 months) versus the nilotinib 24 months consolidation treatment arm (total trial 
time 36 months + 24 months).
10.4.2
Statistical hypothesis, model, and method of analysis
The optimal duration of a nilotinib 300 mg BID treatment will be evaluated using the null 
hypothesis that the rate of no documented confirmed loss of MR4.0, no loss of MMR in the 
first 12 months after nilotinib cessation is the same in both the arms, with an alternative 
hypothesis that this rate is 40% in Arm 1 versus 60% in Arm 2.

H0: p1 = p2, where p1 and p2 are the rates of no documented confirmed loss of MR4.0, no 
loss of MMR in the first 12 months after starting TFR phase in the two arms of the study

H1: p1 ≠ p2, where p1= 0.40 and p2 = 0.60
A two-sided test with = 0.05 will be used to test this hypothesis.
The rate of successful TFR will be presented together with an exact 95% Clopper-Pearson 
confidence interval.
The chi-square test will be carried out to compare the percentage of patients with no 
documented confirmed loss of MR4.0, no loss of MMR in the first 12 months after starting 
TFR phase in the two arms of the study.
A primary efficacy analysis will be performed on the patients entering the TFR phase.
10.4.3
Handling of missing values/censoring/discontinuations
For the primary analysis of the rate of successful TFR, patients dropping out early from the 
study during the TFR phase will be considered as unsuccessful TFR. In case of missing PCR 
assessment at 12 months after starting the TFR phase, the PCR assessments at 10 and 15
months will be taken into account, if available. Details will be provided in the RAP.
10.4.4
Supportive analyses
The primary analysis will be repeated on the FAS and PPS. Patients randomized to Arm 2 not 
entering the TFR phase will be considered as unsuccessful TFR. The same rule described in 
the previous section will be used to deal with any missing PCR assessment at Month 12.
The proportion of patients treatment free (≥MR4.0) after 2 years and after 3 years from 
randomization will also be computed based on the FAS and descriptively summarized by arm.
10.5
Secondary objectives
10.5.1
Key secondary objective(s)
The key secondary objectives for this trial are:

To evaluate the proportion of patients who are eligible to suspend nilotinib therapy by 
achieving and maintaining a sustained ≥MR4.0 for at least 12 months during consolidation 
treatment with nilotinib 300 mg BID:

Determined by the proportion of patients who have achieved a sustained ≥MR4.0
(defined as having four out of five quarterly assessments of ≥MR4.0 by a EUTOS 


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standardized laboratory over the last 12 months and the last assessment before 
randomization is ≥MR4.0) during the consolidation phase of the study

The proportion of patients who are in sustained ≥MR4.0 at 24 months after completing 
the induction/consolidation phase will be calculated by dividing the number of 
patients who have achieved sustained ≥MR4.0 over at least the last 12 months of the 
consolidation phase by the number of patients who entered the study protocol

To assess the achievement of MMR, MR4.0, and MR4.5 during induction/consolidation 
treatment with nilotinib 300 mg BID at the different time points in patients without that 
response at study entry:

Determined by the proportion of patients who achieve MMR, MR4.0, or MR4.5 on the 
study at selected timepoints (every 3 months until Month 24 or 36 depending on the 
randomized arm) during the induction/consolidation phase

The proportion of patients achieving MMR, MR4.0, or MR4.5 at selected timepoints 
will be computed based on the number of patients without that response at baseline

To assess the molecular response in patients during the induction/consolidation phase with 
nilotinib 300 mg BID at the different time points:

Determined by the proportion of patients in MMR, MR4.0, or MR4.5 at selected time 
points (every 3 months until Month 24 or 36 depending on the randomized arm) 
during the induction/consolidation phase of the study

The proportion of patients in MMR, MR4.0 or MR4.5 at selected time points will be 
descriptively analyzed on all patients enrolled

To assess the proportion of patients in TFR at 3, 6, 12, 18, and 24 months after nilotinib 
cessation in the two treatment arms:

Determined by the proportion of patients with no confirmed loss of MR4.0, no loss of 
MMR, and no re-starting of nilotinib therapy within the first 3, 6, 12, 18 and 24 
months following nilotinib cessation

The proportion of patients in TFR will be calculated by dividing the number of 
patients with no confirmed loss of MR4.0, no loss of MMR, and no re-starting of 
nilotinib therapy in the first 3, 6, 12, 18 and 24 months following nilotinib cessation
by the number of patients entering the TFR phase in the two treatment arms

To assess the molecular response in patients after randomization in the two treatment arms:

Determined by the proportion of patients who are in MMR, MR4.0 or MR4.5 at selected 
time points (i.e. Month 3, Month 6, Month 12 and every 3 months thereafter until 
Month 24 or 36 depending on the randomized arm) during the TFR phase in each of 
the two treatment arms

The proportion of patients in MMR, MR4.0 or MR4.5 at selected time points during the 
TFR phase will be descriptively analyzed on the number of patients in the TFR phase 
in each of the two treatment arms

To assess the kinetics of BCR-ABL transcript level during induction/consolidation 
treatment with 300 mg BID nilotinib, during the TFR phase and during the nilotinib re-
treatment phase:


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
Descriptive statistics of BCR-ABL transcript levels (IS) over time separately for the 
induction/consolidation phase, TFR phase, and nilotinib re-treatment phase will be 
provided

To assess the PFS rate after randomization in the two treatment arms:

Failure of PFS is defined as the earliest occurrence of: progression to AP/BC or death 
from any cause

KM estimation of PFS, which is measured from the randomization date to the date of 
the earliest failure event, will be used for this analysis. Patients not known to have 
progressed or died on or before the cut-off date for the KM analysis will have their 
PFS censored at the earlier of the date of their last assessment for patients who are 
still on study and the date of last contact for patients who are in follow-up.

To assess the TFS rate after start of the TFR phase in the two treatment arms:

Failure of TFS is defined as lack of any of the following events: loss of MMR, 
confirmed loss of MR4.0, re-start of nilotinib treatment, progression to AP/BC, or 
death from any cause

KM estimation of TFS, which is measured from the start of TFR phase to the date of 
the earliest failure event, will be used for this analysis. Patients not known to have had 
any of the events on or before the cut-off date for the KM analysis will have their TFS 
censored at the earlier of the date of their last assessment for patients who are still on 
study and the date of last contact for patients who are in follow-up.

To estimate the OS rate after randomization in the two treatment arms:

KM estimation of OS, which is measured from the date of randomization to the date 
of death due to any cause, will be used for this analysis. For patients not known to 
have died on or before the cut-off date, survival time will be censored at the date of 
last contact.

To assess the safety profile of nilotinib during the induction/consolidation phase, the TFR 
phase, and the re-treatment phase (see Section 10.5.3)
10.5.2
Other secondary efficacy objectives
For those patients consenting to participate in the optional Stem cells ENESTPath substudy, 
the following secondary objectives will also be evaluated:

To evaluate the presence and number of LSC and their progenitors in the bone marrow of 
all patients participating in this substudy before and after completing induction and first 
year of consolidation phase (at Visit 8):

The proportion of patients presenting LSC in the bone marrow will be calculated at 
each time point and descriptively analyzed.


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
To evaluate whether a longer treatment period of consolidation with nilotinib (patients in 
Arm 2 versus patients in Arm 1) induces a reduction in the percentage of patients 
presenting LSC and progenitor cells in bone marrow at the end of consolidation phase and 
to quantify this reduction:

The proportion of patients presenting LSC in the bone marrow at the end of the 
consolidation arm (Visit 8 for Arm 1 and Visit 204 for Arm 2) will be descriptively 
analyzed by treatment arm

To perform an exploratory analysis in order to evaluate whether relapse in patients during 
the TFR phase in either arm correlates with the presence of LSC and progenitor cells in 
bone marrow at the end of the consolidation phase and at the time of relapse during TFR.
Please refer to the [Post-Text Supplement 1] to see the objectives of the ‘CML patient’s 
voice’ Italian substudy.
10.5.3
Safety objectives
10.5.3.1
Analysis set and grouping for the analyses
Safety analyses will be based on the SS and presented by study phase. The safety summary 
tables will include only assessments collected no later than 30 days after study treatment 
discontinuation. All safety assessments will be listed, and those collected later than 30 days 
after treatment discontinuation will be flagged.
10.5.3.2 Adverse events
The incidence of treatment-emergent AEs (new or worsening from screening visit) will be 
summarized by MedDRA System Organ Class and Preferred Term, severity (based on 
CTCAE grades), type of AE, and relation to study treatment.
Deaths reportable as SAEs and non-fatal SAEs will be listed by patient and tabulated by type 
of AE and study phase.
Specific safety event categories will be considered. Such categories consist of one or more 
well-defined safety events that are similar in nature and for which there is a specific clinical 
interest in connection with the study treatment.
For each specified safety event category, the number and percentage of patients with at least 
one event that is in the category will be reported.
10.5.3.3 Laboratory abnormalities
For laboratory tests covered by the CTCAE version 4.03, the study’s biostatistician will grade 
laboratory data accordingly. Grade 0 will be assigned for all non-missing values not graded as 
1 or higher. Grade 5 will not be used.
For laboratory tests for which grades are not defined by CTCAE, results will be graded by the 
low/normal/high classifications based on laboratory normal ranges.
The following summaries, split by treatment and study phase, will be generated separately for 
hematology and clinical chemistry:




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Therefore, it is assumed that the percentage of patients without relapse will be 40% in Arm 1, 
and 60% in Arm 2. Considering this, a sample size of 107 patients per group (a total of 214) is 
needed to detect such difference. These calculations are based on a two-sided chi-square test 
at the 0.05 alpha level and with a power of 80%.
Assuming that 5% of patients will be unevaluable after randomization, a total of 226 patients 
will need to be randomized in order to adequately power the study.
Finally, as explained above, assuming that 40% of the patients switched from imatinib to 
nilotinib will achieve ≥MR4.0 at the end of the 12-month induction phase, and will maintain 
this level of MR by the end of the 12-month consolidation phase prior to randomization, a 
total of 565 patients are required for this study.
10.8
Power for analysis of key secondary variables
Not applicable.
11
Ethical considerations and administrative procedures
11.1
Regulatory and ethical compliance
This clinical study was designed, shall be implemented, and will be reported in accordance 
with the International Conference on Harmonization (ICH) Harmonised Tripartite Guidelines 
for GCP, with applicable local regulations (including European Directive 2001/20/EC and US 
Code of Federal Regulations Title 21), and with the ethical principles laid down in the 
Declaration of Helsinki.
11.2
Responsibilities of the investigator and IRB/IEC/REB
The protocol and the proposed ICF must be reviewed and approved by a properly constituted 
IRB/IEC/Research Ethics Board (REB) before study start. A signed and dated statement that 
the protocol and informed consent have been approved by the IRB/IEC/REB must be given to 
Novartis before study initiation. Prior to study start, the investigator is required to sign a 
protocol signature page confirming his/her agreement to conduct the study in accordance with 
these documents and all of the instructions and procedures found in this protocol and to give 
access to all relevant data and records to Novartis monitors, auditors, Novartis Clinical 
Quality Assurance representatives, designated agents of Novartis, IRBs/IECs/REBs, and 
regulatory authorities as required.
11.3
Informed consent procedures
Eligible patients may be included in the study only after providing written (witnessed, where 
required by law or regulation) and IRB/IEC/REB-approved informed consent. Informed 
consent must be obtained before conducting any study-specific procedures (i.e. all of the 
procedures described in the protocol). The process of obtaining informed consent should be 
documented in the patient’s source documents. The date when a patient’s informed consent 
was actually obtained will be captured in their eCRFs.


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Novartis will provide investigators in a separate document with a proposed ICF that is 
considered appropriate for this study and complies with the ICH GCP guideline and 
regulatory requirements. Any changes to this ICF suggested by the investigator must be 
agreed to by Novartis before submission to the IRB/IEC/REB, and a copy of the approved 
version must be provided to the Novartis monitor after IRB/IEC/REB approval.
Women of childbearing potential should be informed that taking the study medication may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirement for the 
duration of the study. If there is any question that the patient will not reliably comply, they 
should not be entered into the study.
Those patients who decide to participate in the optional Stem cells ENESTPath substudy will 
sign a specific ICF, separate from the ICF for the core protocol. Refusal to give consent for 
the stem cells study will not affect eligibility for the main ENESTPath study.
Those patients who decide to participate in the ‘CML patient’s voice’ Italian sub study will 
sign a specific ICF, separate from the ICF for the core protocol. This substudy will be 
conducted in Italy only.
11.4
Discontinuation of the study
Novartis reserves the right to discontinue this study under the conditions specified in the 
clinical study agreement. Specific conditions for terminating the study are outlined in Section 
4.4.
11.5
Publication of study protocol and results
Novartis assures that the key design elements of this protocol will be posted in a publicly 
accessible database, such as clinicaltrials.gov. In addition, upon study completion and 
finalization of the study report, the results of this study will be either submitted for publication 
and/or posted in a publicly accessible database of clinical study results.
Together with the clinical trial team, the DMC chair and the SSMC Chair will also develop 
recommendations for publication of study results, including authorship rules.
All authors must have:

Contributed substantially to the concept, design and/or conduct of the (i.e. patient accrual), 
or to the acquisition, analysis, and interpretation of data, AND

Drafted or critically revised the proposed clinical publication for important intellectual 
content, AND

Approved the final proposed clinical publication for submission, AND

Have intimate knowledge of trial implementation/analysis
Authors may be external or internal to Novartis. There is no predetermined ratio of internal to 
external authors but due consideration will be given to balance.
The details of the publication guidelines are summarized in the ENESTPath publication 
charter.


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11.6
Study documentation, record keeping, and retention of 
documents
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with Section 4.9 of the ICH E6 GCP, and regulatory and institutional 
requirements for the protection of confidentiality of patients. As part of participating in a 
Novartis-sponsored study, each site will permit authorized representatives of the sponsor(s) 
and regulatory agencies to examine (and when required by applicable law, to copy) clinical 
records for the purposes of quality assurance reviews, audits, and evaluation of the study 
safety and progress.
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial. 
Examples of these original documents and data records include, but are not limited to, hospital 
records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or 
evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and complete, 
microfiches, photographic negatives, microfilm or magnetic media, X-rays, and patient files 
and records kept at the pharmacy, laboratories, and medico-technical departments involved in 
the clinical trial.
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site Principal Investigator. The study eCRF is the primary data collection instrument for 
the study. The investigator should ensure the accuracy, completeness, legibility, and 
timeliness of the data reported in the eCRFs and all other required reports. Data reported on 
the eCRF derived from source documents should be consistent with the source documents or 
the discrepancies should be explained. All data requested on the eCRF must be recorded. Any 
missing data must be explained. Any change or correction to a paper CRF should be dated, 
initialed, and explained (if necessary) and should not obscure the original entry. For electronic 
eCRFs, an audit trail will be maintained by the system. The investigator should retain records 
of the changes and corrections to paper CRFs.
The investigator/institution should maintain the trial documents as specified in Essential 
Documents for the Conduct of a Clinical Trial (ICH E6 Section 8) and as required by 
applicable regulations and/or guidelines. The investigator/institution should take measures to 
prevent accidental or premature destruction of these documents.
Essential documents (written and electronic) should be retained for a period of not less than 
15 years from the completion of the clinical trial unless the sponsor provides written 
permission to dispose of them or requires their retention for an additional period of time 
because of applicable laws, regulations, and/or guidelines.
11.7
Confidentiality of study documents and patient records
The investigator must ensure anonymity of the patients; patients must not be identified by 
names in any documents submitted to Novartis. Signed ICFs and the patient enrollment log 
must be kept strictly confidential to enable patient identification at the site.


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11.8
Audits and inspections
Source data/documents must be available to inspections by Novartis or designee or Health 
Authorities.
11.9
Financial disclosures
Financial disclosures should be provided by the study personnel who is directly involved in 
the treatment or evaluation of patients at the site, prior to study start.
12
Protocol adherence
Investigators must ascertain they will apply due diligence to avoid protocol deviations. Under 
no circumstances should the investigator contact Novartis or its agents, if any, monitoring the 
study to request approval of a protocol deviation, as no authorized deviations are permitted. If 
the investigator feels a protocol deviation would improve the conduct of the study this must 
be considered a protocol amendment, and unless such an amendment is agreed upon by 
Novartis and approved by the IRB/IEC/REB it cannot be implemented. All significant 
protocol deviations will be recorded and reported in the Clinical Study Report.
12.1
Amendments to the protocol
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, Health Authorities where required, and the IRB/IEC/REB. 
Only amendments that are required for patient safety may be implemented prior to 
IRB/IEC/REB approval. Notwithstanding the need for approval of formal protocol 
amendments, the investigator is expected to take any immediate action required for the safety 
of any patient included in this study, even if this action represents a deviation from the 
protocol. In such cases, Novartis should be notified of this action and the IRB/IEC/REB at the 
study site should be informed within 10 working days.


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13
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outcome in chronic myelogenous leukemia: Need for new response definitions? Cancer; 
112(4):837-45.
Kantarjian M, Giles F, Gattermann N, et al (2007). Nilotinib (formerly AMN107), a highly 
selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia 
chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib 
resistance and intolerance. Blood 2007; 110: 3540-46.
Larson, R, et al. ENESTnd 5-year (y) update: Long-term outcomes of patients (pts) with 
chronic myeloid leukemia in chronic phase (CML-CP) treated with frontline nilotinib (NIL) 
versus imatinib (IM). Blood 2014 (ASCO Annual Meeting Abstracts); [abstract 7073]
Larson, R, et al. Efficacy and Safety of Nilotinib (NIL) vs Imatinib (IM) in Patients (pts) With 
Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Long-Term 
Follow-Up (f/u) of ENESTnd. Blood 2014 (ASH Annual Meeting Abstracts); [abstract 4541] 
(Poster Presentation)
le Coutre P, Ottmann OG, Giles F, et al (2008). Nilotinib (formerly AMN107), a highly 
selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or 
intolerant accelerated-phase chronic myelogenous leukemia. Blood; 111:1834-39.
le Coutre, et al (2004). Pharmacokinetics and cellular uptake of imatinib and its main 
metabolite CGP74588. Cancer Chemother Pharmacol; 53:313-23.
Mahon FX, Rea D, Guilhot J, et al (2010). Discontinuation of imatinib in patients with 
chronic myeloid leukemia who have maintained complete molecular remission for at least 2 
years: the prospective, multicentre, Stop IMatinib (STIM) trial. Lancet Oncol; 11:1029-35.
Manley PW, et al (2010). Extended kinase profile and properties of the protein kinase 
inhibitor nilotinib. Biochim Biophys Acta; 1804(3):445-53.


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O’Dwyer ME, Swords RT, Giles F, et al (2009). Nilotinib 300 mg twice daily is effective and 
well tolerated as first line treatment of Ph-positive chronic myeloid leukemia in chronic phase: 
Preliminary results of the ICORG 08-02 phase 2 study. Blood (ASH Annual Meeting 
Abstracts); 112(22); Abstract 3294 (poster).
Press RD, Galderisi C, Yang R, et al (2007). A half-log increase in BCR-ABL RNA predicts a 
higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced 
complete cytogenetic response. Clin Cancer Res; 13:6136-43.
Ross DM, Branford S, Seymour JF, et al (2010). Patients with chronic myeloid leukemia who 
maintain a complete molecular response after stopping imatinib treatment have evidence of 
persistent leukemia by DNA PCR. Leukemia; 24:1719-24.
Rosti G, Castagnetti F, Palandri F, et al (2009). Nilotinib 800mg daily as front line therapy of 
Ph+ chronic myeloid leukemia: Dose delivered and safety profile for the GIMEMA CML 
working party. Blood (ASH Annual Meeting Abstracts);112 (22); Abstract 2205 (poster).
Rosti G, Palandri F, Castagnetti F, et al (2009). Nilotinib for the frontline treatment of Ph+ 
chronic myeloid leukemia. Blood; 114:4933-38.
Saglio G, Kim DW, ENESTnd Investigators, et al (2010). Nilotinib versus imatinib for newly 
diagnosed chronic myeloid leukemia. N Engl J Med; 17;362(24):2251-9.
Sawyers CL (1999). Chronic myeloid leukaemia. N Engl J Med; 340(17):1330-40.
van Etten RA (2004) Mechanisms of transformation by the BCR-ABL oncogene: new 
perspectives in the post-imatinib era. Leukemia Res; 28(suppl 1):21-8.
Weisberg E, Manley P, Breitenstein W, et al (2005). Characterization of AMN107, a selective 
inhibitor of native and mutant Bcr-Abl. Cancer Cell; 7:129-41.
White DL, Saunders VA, Dang P, et al (2006). OCT-1-mediated influx is a key determinant 
of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is 
the cause of low in vitro sensitivity to imatinib. Blood; 108(2):697-704.
For the ‘CML patients' voice' Italian substudy, please refer to the Post text Supplement 1


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14
Appendices
14.1
Appendix 1 List of CYP3A4 inducers and inhibitors
14.1.1
List of medications metabolized by CYP3A4, strong, moderate and 
weak inhibitors of CYP3A4 to be used with caution
CYP3A4 substrates permitted but 
patients should be carefully monitored 
for drugs indexed 1 and 2
Strong 
inhibitors
Moderate
inhibitors
Weak inhibitors
alfentanil1,2
fentanyl2
clarithromycin
aprepitant
alprazolam
fluticasone1
diergotamine2
conivaptan
atazanavir
AMD070
cyclosporine2
adinazolam
indinavir
cimetidine
amlodipine
maraviroc1
alprazolam
itraconazole
ciprofloxacin
azithromycin
midazolam1
amlodipine
ketoconazole
darunavir
bicalutamide
alpha-
dihydroergocryptine1
aripiprazole
lopinavir
diltiazem
chlorzoxazone
sildenafil1
chlorpheniramine
mibefradil
erythromycin
cilostazol
tipranavir1
diazepam
nefazodone
fluconazole
cyclosporine
triazolam1
estazolam
nelfinavir
grapefruit juice
fluvoxamine
perospirone1
nisoldipine
posaconazole
imatinib
ginkgo
darifenacin1
quinine
ritonavir
tofisopam
goldenseal
ebastine1
trazodone
saquinavir
verapamil
isoniazid
eletriptan1
nitrendipine
telithromycin
lacidipine
eplerenone1
mevastatin
troleandomycin
M100240
everolimus1
lovastatin1
voriconazole
oral contraceptives
felodipine1
atorvastatin1
peppermint oil
brotizolam1
simvastatin1
propiverine
budesonide1
fluvastatin
ranitidine
buspirone1
ranolazine
sirolimus1,2
roxithromycin
ergotamine2
Seville orange juice
tabimorelin
1 Sensitive substrates: drugs whose plasma AUC values have been shown to increase 5-fold or higher when co-
administered with a potent inhibitor of the respective enzyme.
2 Substrates with narrow therapeutic index (NTI): drugs whose exposure-response indicates that increases in their 
exposure levels by the concomitant use of potent inhibitors may lead to serious safety concerns (e.g., Torsades 
de Pointes).
Note:

Inhibitor classification:

Strong inhibitors may result in a substrate AUC > 5-fold increase.

Moderate inhibitors may result in a substrate AUC ≥ 2-fold increase and < 5-fold 
increase.


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
Weak inhibitors may result in a substrate AUC ≥ 1.25-fold increase and < 2-fold 
increase.
This list is compiled based on the FDA’s “Guidance for Industry, Drug Interaction Studies”, 
the Indiana University School of Medicine’s Drug Interactions Database, and the University 
of Washington’s Drug Interaction Database. This list may not be comprehensive and may be 
updated periodically. Refer to Novartis Oncology Clinical Pharmacology Internal 
Memorandum, Drug-drug interactions (DDI) Database (last updated 30 August 2010) for 
update or more details.


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14.2
Edinburgh Claudication Questionnaire

SAP_001.pdf: 


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Document History – Changes compared to previous version of RAP module 3.
Version
Date
Changes
1.0
13-Jan-2020
Initial draft
1.1
05-Mar 2020
Draft v 1.1, Added analysis 
1.2
30-Mar-2020
Format Changes
1.3
06-Apr-2020
Adding LSC sub-study abstract analysis
1.4
01-July-2020
Updating according to DR1 comments
1.5
28-Sep-2020
Adding LSC FAS definition
1.6
06-Oct-2020
Adding SSMC extra analysis
Pre- Final
07-Oct-2020
Finalize document
Final
09-Oct-2020
Minor cosmetics update and final version for CSR
Addendum
04-Jan-2021
Sensitivity analysis, excluding SDV (not done) involved visits
KM analysis of PFS and TFS based on eCRF captured variable 
‘Progression to AP/BC ’
Addendum 
V1.1
29-Jan-2021
Section 4.8, excluding Safety output Sensitivity analysis outputs not 
affected by the SDV record exclusion of specific visits, since they are 
based on Start and Stop dates independently of standard study visits: 
Duration of exposure, relative dose intensity, dose reduction/interruption 
of study drug treatment, Concomitant medication, AEs , TEAES, CVEs 
and Medical History.
Final
16-03-2021
Final version


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Table of contents
1
Statistical methods planned in the protocol.........................................................................8
2
Statistical and analytical plans.............................................................................................8
2.1
Overview of study design........................................................................................8
2.2
Study objectives.....................................................................................................10
2.3
General strategies of data presentation..................................................................12
2.4
Assessment windows, baseline and post-baseline definitions, missing data 
handling .................................................................................................................12
2.4.1
Time-windows.......................................................................................12
2.4.2
Assessment windows ............................................................................15
2.4.3
Baseline and post-baseline definitions..................................................16
2.4.4
Last contact date....................................................................................18
2.4.5
Cut-off date ...........................................................................................18
2.4.6
End of Study (EoS) visit .......................................................................18
2.5
Missing data handling............................................................................................18
2.6
Analysis proportions..............................................................................................19
2.6.1
Analysis of Molecular response proportions.........................................19
2.6.2
Analysis of time-to-event endpoints .....................................................20
2.6.3
Adjustment for covariates .....................................................................20
2.7
Other definitions....................................................................................................20
2.7.1
Treatment periods and treatment emergent periods..............................20
2.7.2
TFR phase and emergent adverse events ..............................................20
2.7.3
Cardiovascular risk factors....................................................................21
2.7.4
Study medication...................................................................................22
2.7.5
Duration of exposure.............................................................................22
2.7.6
Relative dose intensity ..........................................................................23
2.7.7
Molecular responses..............................................................................24
2.7.8
Progression-free survival ......................................................................24
2.7.9
Treatment-free survival.........................................................................25
2.7.10
Overall survival.....................................................................................25
2.7.11
LSC detected cases................................................................................25
3
Subjects and treatments .....................................................................................................28
3.1
Definition of analysis sets......................................................................................28
3.2
Patient disposition and characteristics at screening...............................................29
3.2.1
Patient disposition.................................................................................29
3.2.2
Screen Failures......................................................................................31


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3.2.3
Study discontinuation............................................................................31
3.2.4
Demographics and baseline characteristics variables ...........................32
3.2.5
Disease history ......................................................................................34
3.2.6
Medical history/current medical condition ...........................................34
3.2.7
Cardiovascular risk factors....................................................................34
3.3
Prior and concomitant medications/non-drug therapies ........................................36
3.3.1
Description of CV risk factors based on medical history, laboratory 
parameters and vital signs at baseline...................................................36
3.4
Study medication ...................................................................................................37
3.4.1
Duration of exposure.............................................................................38
3.4.2
Relative dose intensity ..........................................................................38
3.4.3
Dose reduction and interruption............................................................38
3.4.4
Dosage administration record ...............................................................38
3.5
Protocol deviations ................................................................................................38
4
Efficacy evaluation............................................................................................................38
4.1
Molecular response................................................................................................39
4.2
Subgroup definition ...............................................................................................39
BCR-ABL (IS) ratio at baseline ............................................................................39
BCR-ABL (IS) ratio at Month 3............................................................................39
Molecular response up to Month 3 (suggested by SSMC members) ....................39
Halving time of BCR-ABL (IS) ratio....................................................................40
Time since initial diagnosis of CML .....................................................................40
Sokal risk group.....................................................................................................40
4.3
Kinetics of BCR-ABL(IS) transcript levels...........................................................41
4.4
Progression free survival after entering the TFR phase.........................................41
4.5
Treatment free survival after entering the TFR phase...........................................41
4.6
Overall survival after Randomization....................................................................41
4.7
Other efficacy assessments....................................................................................42
4.8
SDV sensitivity analysis........................................................................................42
5
Pharmacokinetic evaluations.............................................................................................43
6
Safety evaluation ...............................................................................................................43
6.1
Adverse events.......................................................................................................43
6.2
Laboratory abnormalities.......................................................................................45
6.3
Vital signs..............................................................................................................46
6.4
Electrocardiograms (ECGs)...................................................................................47
6.5
Echocardiography (cardiac imaging).....................................................................47


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6.6
Survival Follow-up ................................................................................................47
6.7
Safety Follow-up ...................................................................................................48
6.8
LSC sub-study analysis..........................................................................................48
7
Other topics .......................................................................................................................49
8
Sample size calculation .....................................................................................................49
9
References .........................................................................................................................50


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List of abbreviations
ABL
Abelson leukemia virus
AE
Adverse Event
AESI
Adverse Event of Special Interest
ALT
Alanine aminotransferase/glutamic pyruvic transaminase/GPT
ANC
Absolute Neutrophil Count
AP
Accelerated phase
AST
Aspartate aminotransferase/glutamic oxaloacetic transaminase/GOT
BC
Blast Crisis
BCR-ABL
BCR-ABL oncoprotein product of BCR-ABL fusion gene
BID
bis in diem/twice a day
CCyR
Complete cytogenetic response
CHR
Complete hematological response
CML
Chronic myeloid leukemia
CP
Chronic phase
eCRF
Case Report/Record Form; the term CRF can be applied to either EDC or Paper
CSR
Clinical study report
CTCAE
NCI Common Terminology Criteria for Adverse Events
CV
Cardiovascular
CVEs
Cardiovascular events
DI
DMC
Dose Intensity
Data Monitoring Committee
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
EDC
Electronic Data Capture
EoS
End of Study
EUTOS
European Treatment Outcome Study
FAS
Full Analysis Set
FDA
Food and Drug Administration (USA)
GFR
Glomerular Filtration Rate
ICE
Ischemic cerebrovascular events
IHD
Ischemic heart disease
IS
International scale
LLN
Lower limit of normal
LVEF
Left ventricular ejection fraction
MedDRA
Medical dictionary for regulatory activities
MMR
Major molecular response
MR
Molecular response
MR4 0
4.0 log reduction on international scale (IS)
MR4 5
4.5 log reduction on international scale (IS)


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NEU
Neutrophils
PAOD
Peripheral arterial occlusive disease
PD
Protocol deviation
PDI
Planned Dose Intensity
PCR
Polymerase chain reaction
Ph
Philadelphia chromosome
Ph+ CML
Philadelphia chromosome positive chronic myeloid leukemia
PFS
Progression Free Survival
PPS
Per Protocol Set
PT
Preferred Term
RDI
Relative Dose Intensity
SAE
Serious adverse event
SDV
Source Data Verification
SOC
System Organ Class
SMQ
Standardized MedDRA Query 
TEAE
Treatment Emergent Adverse Event
TFR
Treatment free remission
TFS
Treatment free survival
TKI
Tyrosine kinase inhibitor
ULN
Upper limit of normal
VAP
Validation and planning
WBC
White blood cell


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1
Statistical methods planned in the protocol
This document contains details of the statistical methods which will be applied for the CSR
analysis for the CAMN107AIC05 clinical trial.
The Primary objective of the CSR is to assess the optimal duration of consolidation treatment 
with nilotinib 300 mg BID in order that patients remain in treatment-free remission (≥MR4.0) 
without molecular relapse 12 months after entering the TFR phase
2
Statistical and analytical plans
The data will be analyzed by 
 according to the data analysis section 10 of the study 
protocol which is available in Appendix 16.1.1 of the CSR.  Important information is given in 
the following sections and details are provided, as applicable, in Appendix 16.1.9 of the CSR.
Analyses will be conducted on all enrolled patients (Full Analysis Set, excluding patients 
without major protocol deviation) and all their data will be used for the analyses.
Primary Endpoint analysis will be performed for both FAS and PPS (FAS, excluding patients 
without major protocol deviation.
Data will be summarized with respect to demographic and baseline characteristics and safety 
observations and measurements. Assessment of molecular response will also be summarized.
2.1
Overview of study design
The CAMN107AIC05 study is a prospective, randomized, open label, multicenter, two arm 
Phase III study that includes a 12-month induction phase, followed by a 12 or 24 months
consolidation phase (dependent on randomization), and a 36 or 24 month TFR phase 
respectively, adding to 5 year study duration for the individual patient.
This study aims to assess the optimal duration of nilotinib 300 mg twice daily (BID, bis in die)
consolidation treatment, in order that patients remain in TFR (≥molecular response [MR]4.0) 
12 months after starting the TFR phase of the study. Patients with chronic myeloid leukemia in 
chronic phase (CP CML) who have received 24 months of first line imatinib treatment, and who 
have failed to achieve the molecular response threshold for treatment cessation (≥MR4.0) have 
a 50% greater chance of achieving this level of molecular response by switching to nilotinib; 
however the optimal duration of consolidation treatment with nilotinib to ensure the highest 
rate of patients remaining in ≥MR4.0 after suspending treatment is not yet known. This study 
therefore aims to assess the potential impact of two durations of consolidation treatment with 
nilotinib, i.e. 12 months versus 24 months, on molecular relapse rate in the first 12 months of 
the TFR phase. Eligible patients are adults with a confirmed diagnosis of chronic phase Ph+ 
and/or BCR ABL+ CML who have been treated with first line imatinib for 2 calendar years or 
more and are in complete cytogenetic response (CCyR). Patients must not have achieved 
≥MR4.0 at study entry, as assessed/confirmed by a local or a EUTOS laboratory.
620 patients have been enrolled into the study and were treated with nilotinib 300 mg BID for 
24 months. Following the 24 months of treatment, patients in sustained molecular response for 
at least the last 12 months will be randomized on a 1:1 basis to either:


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
Suspend nilotinib treatment immediately and enter the TFR phase (Arm 1; the nilotinib 
24 months treatment arm); or

Continue nilotinib treatment for a further 12 months then suspend treatment and enter 
the TFR phase (Arm 2; the nilotinib 36 months treatment arm).
Treatment-phases will be labelled, using as reference time point Randomization visit, as:
“Induction/consolidation treatment phase”, for both treatment arms from the date of 
Informed consent until Randomization visit.
“Post-randomization treatment phase (ARM2)” for the 12-month additional treatment 
for treatment arm 2, from the date of Randomization visit+ 1 day.
Patients not achieving a sustained molecular response at 24 months (and subsequently at 36 
months if previously randomized to the treatment arm with 1 year additional consolidation) will 
exit the study and will be treated at the discretion of the Investigator according to standard 
practice. Information on survival, stem cell transplantation, and on the status of the patient’s 
disease (i.e. disease progression to AP (accelerated phase)/BP (blastic phase) according to 
protocol definition, tyrosine kinase inhibitor (TKI) treatment) will be collected until death, or 
until 5 years from study entry, whichever comes first.
Patients relapsing during the TFR phase will enter the nilotinib re-treatment phase of the study 
and will be re-treated with the same dose of nilotinib as they were on before the TFR phase (i.e. 
the re-treatment dose will be nilotinib 300 mg BID or a lower dose of nilotinib if this was 
reduced in the consolidation phase before entering the TFR phase). These patients will remain 
on study until the completion of the 5 years study period.
Details on the visit schedules and assessments are reported in Section 7 of the study protocol.
Optional Leukemic Stem Cells ENESTPath sub-study:
The Stem cells ENESTPath sub-study aims to add the determination of Ph+ stem cells in bone 
marrow in those patients consenting to participate in this sub-study, at the following time points:
a) At the screening visit, before starting nilotinib treatment
b) After 24 months of nilotinib treatment at Visit 8
c) After 36 months of nilotinib treatment, only in patients with 12 months additional of’ 
consolidation treatment (Arm 2) at Visit 204
d) If the patient relapses during the TFR phase, before re-starting the treatment with 
nilotinib.
A 10 mL bone marrow sample is collected at each time point and sent to 
 
 for immunophenotype analysis, FACS (fluorescence 
activated cell sorting) cell purification, in situ hybridization, and RT-PCR. Measurement and 
quantification will be performed by flow cytometry in a bone marrow purified population of 
stem cells in order to detect the presence of leukemic Ph+ cells or BCR-ABL transcript levels 
(evaluated by fluorescent in situ hybridization [FISH] or RT-PCR).


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2.2
Study objectives
The primary objective of the study is to assess the optimal duration of consolidation treatment 
with nilotinib 300 mg BID in order that patients remain in treatment free remission (TFR) with 
a molecular response of 4.0 or higher (≥MR4.0) without molecular relapse 12 months after 
entering the TFR phase. 
The secondary objectives of the study are:

To evaluate the proportion of patients who are eligible to suspend nilotinib therapy by 
achieving and maintaining sustained ≥MR4.0 for at least 12 months during consolidation 
phase with 300 mg BID nilotinib;

To assess the kinetics of molecular response of patients during induction/consolidation 
treatment with 300 mg BID nilotinib;

To assess the kinetics of molecular response in patients during the TFR phase of the 
study in both treatment arms;

To assess progression-free survival (PFS) rate after randomization in both treatment 
arms;

To assess treatment-free survival (TFS) rate after randomization in both treatment arms;

To estimate overall survival (OS) rate after randomization in both treatment arms;

To assess the safety profile of nilotinib during the induction/consolidation phase, the 
TFR phase, and during the re-treatment phase.
For those patients consenting to participate in the optional Stem cells ENESTPath substudy 
included in Amendment 1, the following objectives will be also evaluated:

To evaluate the presence and amount of leukemic stem cells (LSC) and their progenitors 
in the bone marrow of all patients participating in this substudy before and after 
completing induction and first year of consolidation phase (at Visit 8);

To evaluate if prolonging treatment period of consolidation with nilotinib (patients in 
Arm 2 versus patients in Arm 1) causes a reduction in the percentage of patients 
presenting LSC and progenitor cells in bone marrow at the end of the second year of 
consolidation phase;

To perform an exploratory analysis in order to evaluate if relapse in patients during the 
TFR phase in either arm correlates with the presence of LSC and progenitor cells in 
bone marrow at the end of the consolidation phase.

To check the correlation of the response after switch from Imatinib to Nilotinib with the 
persistence of LSCs in the blood.


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Additionally, for LSC-sub-study data the following objectives were set:

To evaluate LSC detected cases, by Prior Imatinib exposure, Major Molecular Response 
Age and Sokal score for Randomized vs Not Randomized.

To evaluate the presence and amount of leukemic stem cells (LSC) in Arm 1m Arm 2, 
Randomized, Not Randomized and Total group of LSC detected cases.
Objective
Endpoint
Analysis
To evaluate the presence and 
number of LSC and their 
progenitors in the bone marrow of 
all patients participating in this sub-
study before and after completing 
induction and first year of 
consolidation phase (at Visit 8 ).
To evaluate whether prolonging 
the treatment period of 
consolidation with nilotinib 
(patients in Arm 2 versus patients 
in Arm 1) induces a reduction in 
the percentage of patients 
presenting LSC and progenitor 
cells in bone marrow at the end of 
the second year of the 
consolidation phase (Visit 204 for 
Arm 2 versus Visit 8 for Arm 1);
Proportion of patients with 
presence of Ph+ LSC in bone 
marrow (CD34+/CD38+ progenitor 
cells, CD34+/CD38− stem cells, 
and Immunophenotypically 
aberrant CD34+ stem cells [the 
last ones only if detectable]) at 
screening and at Visit 8, and 
Immunophenotypically aberrant 
CD34- stem cells.
Proportion of patients with 
presence of Ph+ LSC in bone 
marrow (CD34+/CD38+ progenitor 
cells, CD34+/CD38− stem cells, 
and Immunophenotypically 
aberrant CD34+stem cells [the last 
ones only if detectable]) at the end 
of consolidation arm (Visit 8 for 
Arm 1 and Visit 204 for Arm 2) and 
Immunophenotypically aberrant 
CD34- stem cells.
The percentage of patients 
presenting Ph+ LSC in bone 
marrow will be calculated at each 
time point and will be presented by 
descriptive statistics. 
Descriptive statistics.
To perform an exploratory analysis 
in order to evaluate
whether relapse in patients during 
the TFR phase in
either arm correlates with the 
presence of LSC and
progenitor cells in bone marrow at 
the end of the
consolidation phase and at the 
time of relapse during
TFR.
Proportion of patients with or 
without molecular
relapse in the first year of TFR in 
either arm by
presence of LSC in bone marrow 
(CD34+/CD38+
progenitor cells, CD34+/CD38− 
stem cells, and
CD34+/CD56+ aberrant stem cells 
[the last ones only
if detectable]) at Visit 8 and at the 
time of relapse
during TFR.
Descriptive statistics


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2.3
General strategies of data presentation 
All categorical data will be summarized by frequencies and percentages, with the denominator 
being the total number of patients included in the analysis population, or the number of patients 
with available data (as specified in RAP Module 7). 
Continuous data will be summarized with either standard descriptive statistics (i.e. the number 
of non-missing data, arithmetic mean, standard deviation, median, 25th and 75th percentiles, 
minimum and maximum), or will be collapsed into categorical data and summarized as 
categorical data.
Pre-randomization data will be presented for Arm1, Arm2, Not Randomized and Total.
Shells of the tables, listings and figures are described in Module 7 of the RAP.
2.4
Assessment windows, baseline and post-baseline definitions, 
missing data handling
2.4.1 Time-windows
For analysis purposes, time-windows will be defined. The time-windows are defined so that 
there are no gaps between the planned assessments, i.e. every assessment, including additional 
unscheduled assessments, would be assigned to one specific time-point. If there is more than 
one assessment within the time-window, the last available assessment in that time-window will 
be used. For all time-windows after baseline, only values after first dose of study drug will be 
used. 

Pre randomization induction/consolidation phase (Arm1, Arm2 and Not Randomized), 
time-windows are defined as starts at first day of study treatment and ends with 
randomization date. For Not-Randomized patients V400 (End of Induction 
/Consolidation visit) will be used.

For post-randomization consolidation phase (Arm 2 only), time-windows are defined 
as starting at randomization date + 1 day and ending with the last day of study 
treatment (12 months after first randomization + 1 day).

For TFR phase, time-windows are defined based on first day of TFR phase (i.e. last 
day of study drug intake from induction/consolidation phase for Arm1 or last day of 
study drug intake from post-randomization consolidation phase for Arm2, as described 
in section 2.8.4 + 1 day). 

For re-treatment phase, time-windows are defined based on first day of re-treatment (i.e. 
first day of study drug intake when patient re-starts study drug as described in section 
2.8.4). The following table shows the time-windows for the analyses of molecular 
response based on the planned assessment schedule.


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Time-windows presented in Table 1 below are calculated using the following formula:
-
When assessments are planned every month: Day ([xx-0.5]*30.4375 + 1) – Day 
([xx+0.5]*30.4375) where xx is the month of the visit
-
When assessments are planned every 2 months: Day ([xx-1]*30.4375 + 1) – Day 
([xx+1]*30.4375) where xx is the month of the visit 
-
When assessments are planned every 3 months: Day ([xx-1.5]*30.4375 + 1) – Day 
([xx+1.5]*30.4375) where xx is the month of the visit 
-
For Day 1 and Week 6 time-window of re-treatment phase, Week 6 starts at Day ([6-
3]*7 + 1) and ends where Month 3 starts. Day 1 time-window ends the day before 
Week 6 starts (day 21).
Depending on the study phase, time-windows are defined based on reference start dates defined 
in section 2.4.2 Error! Reference source not found. below.
Table 1 Definition of time-windows for molecular response
Planned 
visit
Study Day
Time-window
Comment
Induction/Consolidation 
phase
Month 3
Day 91
2 -
136
Month 6
Day 183
137 -
228 
Month 9
Day 274
229 -
319 
Month 12
Day 365
320 -
410 
Pre-Randomization
Month 15
Day 457
411 -
502 
Month 18
Day 548
503 -
593 
Month 21
Day 639
594 -
684 
Month 24
Day 731
685 -
776 ^
Month 27$
Day 822
777 -
867 
Month 30$
Day 913
868 -
959
Post- Randomization
Month 33$
Day 1004
960 -
1050
Month 36$
Day 1096
1051 -
1141 ^
TFR phase
Month 1
Day 30**
1 -
46#
Month 2
Day 61
47 -
76#
Month 3
Day 91
77 -
107#
Month 4
Day 122
108 -
137#
Month 5
Day 152
138 -
167#
Month 6
Day 183
168 -
213#
Month 8
Day 244
214 -
274#
Month 10
Day 304
275 -
335#
Month 12
Day 365
336 -
411#
Month 15
Day 457
412 -
502#
Month 18
Day 548
503 -
594#


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Month 21
Day 639
595 -
685#
Month 24
Day 731
686 -
776#
Month 27$$
Day 822
777 -
867#
Month 30$$
Day 913
868 -
959#
Month 33$$
Day 1004
960 -
1050#
Month 36$$
Day 1096
1051 -
1141#
Re-treatment 
phase
Day 1
Day 1***
1 -
21
Week 6
Day 42
22 -
67
Month 3
Day 91
68 -
137
Month 6
Day 183
138 -
228
Month 9
Day 274
229 -
320
Month 12
Day 365
321 -
411
Month 15
Day 457
412 -
502
Month 18
Day 548
503 -
594
Month 21
Day 639
595 -
685
Month 24
Day 731
686 -
776
Month 27$$
Day 822
777 -
867
Month 30$$
Day 913
868 -
959
Month 33$$
Day 1004
960 -
1050
Month 36$$
Day 1096
1051 -
1141
* Reference start day is the first date of study drug exposure.
** Reference start day is the first day of TFR phase
*** Reference start day is the first day of re-treatment phase (i.e. 
+ 1 day after study drug intake when patient re-starts study drug).
The presence and number of LSC and their progenitors in the bone marrow will be summarized 
for all enrolled patients participating in this sub-study before and after completing induction 
and the first year of the consolidation phase (at Visit 8 - Month 24), at the end of the second 
year of the consolidation phase (at Visit 204 - Month 36 for Arm 2). 
Table 2 Definition of time-windows for LSC assessments
Text used 
in TLF
Planned visit 
Study Day
Time-
window
Screening (Re-screening) 
Baseline
Day 0
Day 0
<=1 
12th month of consolidation phase
Month 24  
V8-Month 24
Day 731
685 -776 ^
24th month of consolidation phase Arm 2 
Month 36  
V202- Month 36$
Day 1096
1051 -1141 @
^Randomization date or V400 for Not Randomized patients 
@ Last day of study treatment (12 months after randomization date +1 
day).
$ for patients in Arm 2 only.
# or last day before study drug re-start


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Time window will be used, considering no gap should be allowed compared to the planned visit. 
It will permit to exclude visits performed long after the planned visit date. 
Time-windows presented in Table 3 below are calculated using the following formula:
-
Assessments are planned every 3 months: Day ([xx-1.5]*30.4375 + 1) – Day 
([xx+1.5]*30.4375) where xx is the month of the visit 
Table 3 Definition of time-windows for Survival follow-up
Planned 
visit
Study Day
Time-window
Survival follow-up
Month 3
Day 91
2 -
136
Month 6
Day 183
137 -
228 
Month 9
Day 274
229 -
319 
Month 12
Day 365
320 -
410 
Month 15
Day 457
411 -
502 
Month 18
Day 548
503 -
593 
Month 21
Day 639
594 -
684 
Month 24
Day 731
685 -
776 
Month 27
Day 822
777 -
867 
Month 30
Day 913
868 -
959
Month 33
Day 1004
960 -
1050
Month 36
Day 1096
1051 -
1141 
Month 39
Day 1187
1142 -
1233
Month 42
Day 1278
1234 -
1325
Month 45
Day 1370
1326 -
1415
Month 48
Day 1461
1416 -
1507
Month 51
Day 1552
1508 -
1598
Month 54
Day 1644
1599 -
1690
Month 57
Day 1735
1691 -
1781
Month 60
Day 1826
1782 -
1873
* Reference start day is the first day of survival follow-up.
2.4.2
Assessment windows 
Safety assessments will be performed at the following time-points: 
-
Screening (D-28 to D0)
-
Baseline (D1) 
-
Every 3 months during the induction/consolidation phase 
-
End of Phase (EOP) visit
At each of the visit times stated above, peripheral blood will be taken for BCR-ABL RQ-PCR 
assessment (performed in EUTOS standardized laboratory) and hematological assessments.


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Details on safety and efficacy assessments are reported in section 7 of the protocol.  
For analysis purposes time-windows will be defined for the RQ-PCR, bone marrow, FISH test 
and biological assessments over the induction/consolidation phase.
The time-windows are defined so that there are no gaps between the planned assessments, i.e. 
every assessment, including additional unscheduled assessments, would be assigned to one 
specific time-point. If there is more than one assessment within the time-window, the last 
available assessment in that time-window will be used. For all time-windows after baseline, 
only values after first dose of study drug will be used. Time-windows are defined based on first 
study drug intake date (study day 1).
The following table shows the time-windows for the analyses of molecular response based on 
the planned assessment schedule.
Table 2 Time-window for analyses of RQ-PCR, bone marrow, FISH test and biological 
assessments
Planned Assessment
Time-window
Baseline
see definition in 2.5.2
Month 3 – Day 91
Day 2 – Day 136
Month 6 – Day 182
Day 137 – Day 228
Month 9 – Day 273
Day 229 – Day 319
Month xx – Day (xx*30.4375)
Day ([xx-1.5]*30.4375 + 1) –
Day ([xx+1.5]*30.4375)
    xx = Every 3 months until 24 months for Arm 1 and until 36 months for Arm 2.   
2.4.3
Baseline and post-baseline definitions
For all safety and efficacy evaluations the last available assessment before or on the date of start 
of study treatment is taken as the “baseline” assessment. If patients have no value as defined 
below, the baseline result will be missing. The study baseline is the same baseline as defined 
for the induction/consolidation phase. Except if it is specified differently, the term baseline will 
always refer to study baseline. The first day of start of study treatment is taken as “Day 1”.  
Pre randomization Induction/consolidation phase:
The last available assessment before or on the first day of nilotinib intake during 
induction/consolidation phase will be defined as the “baseline” assessment of the 
induction/consolidation phase. 
The first day of start of study treatment is taken as “Day 1”.  
For adverse event, the day 1 will be considered as part of the post-baseline in the
induction/consolidation phase.


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Induction/consolidation phase end date corresponds to the last study drug administration date 
occurring before randomization/eligibility visit, or on the maximum date between:
-
Randomization visit (date of visit 9) for Arm 1, visit 205 for Arm 2, 
and the
-
End of induction/consolidation date (i.e. V400-EOP-ind/con date) for Not Randomized.     
Pre-randomization induction/consolidation phase (CONS1) will be used for summary of AE. It 
corresponds to the 24 months of induction/consolidation phase (i.e. up to randomization) for 
arm 1 and arm 2.
Post-randomization consolidation for arm 2 (CONS2):
The randomization date + 1 day will correspond to the day 1 of this Post randomization 
consolidation phase. This sub-phase ends as defined for the end of induction/consolidation 
phase for arm 2. 
Treatment-free remission phase:
The last available assessment before the first day of TFR phase (i.e. last day of nilotinib intake 
+ 1 day) will be defined as the “baseline” assessment of the TFR phase. 
The end date of TFR phase corresponds to the day of the first administration of re-treatment 
phase, defined as first study drug administration occurring after or on the maximum date 
between the end of TFR phase and the 1st visit from re treatment visit 301-RT day 1 date.
Any assessment occurring between the end date of induction/consolidation phase + 1 day and 
the end date of TFR will be considered as part of post-baseline in TFR phase.
Re-treatment phase:
The last available assessment before or on the end date of TFR phase (i.e. 1st day of re-treatment 
planned at visit V401-EOP-TFR) will be defined as the “baseline” assessment of the re-
treatment phase. 
Start date of re-treatment phase corresponds to the end date of TFR phase + 1 day.
For the purpose of biochemistry/hematology shift tables, a “baseline” assessment will be used 
as mentioned above. If patients have no value as defined above, the baseline assessments will 
be missing.
For adverse event, the Day -1 of re-treatment phase (i.e. Day 1 of restart of nilotinib) will be 
considered as part of the post-baseline re-treatment phase.
Four study days will respectively be defined based on the reference start dates mentioned below:
1. Start of study drug exposure
2. Randomization date
3. Start of TFR phase date
4. Start of re-treatment phase date
Study days will be calculated from the reference start dates as follows: 

If the date of the event is on or after the reference date then: 
Study Day = (date of event – reference date) + 1.


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
If the date of the event is prior to the reference date then: 
Study Day = (date of event – reference date).
Study days will be used to show start/stop day of assessments and events in each phase as 
applicable. 
2.4.4
Last contact date
The last contact date will be derived as the maximum date when the patient is known to be alive.
All dates from the databases will be checked (e.g. actual date of visit, laboratory assessment, 
AE, date of discontinuation, etc.) to determine the last contact date.
2.4.5
Cut-off date
Cut-off date will be Last Patient Last Visit (LPLV) is scheduled.
2.4.6
End of Study (EoS) visit 
End of study (EoS) visit where safety assessments if any will be collected, is planned when 5-
years of study is completed. In case patient discontinued the study, EoS visit should be done 
immediately. When patient will complete the five years of study EoS visit will be performed 
without any time window.
2.5
Missing data handling
Throughout the study reasonable attempts will be made to limit the amount of missing data. 
However missing data will not be imputed, unless imputation is needed to perform specific 
analyses (e.g., for a dose administration record (DAR) with missing end date or end date after 
the cut-off date, the cut-off last contact date needs to be imputed as an end date to allow for 
calculation of treatment exposure duration and dose intensity). If it is required to impute an end 
date, the imputed date will be displayed and flagged in the appropriate listing, if produced. 
Imputation rules for missing dates (if applied) will be defined in the RAP Module 8 before the 
soft database lock.
The default rule for missing date imputation is the following:
-
Day missing will be replaced by 15;
-
Day & month missing will be replaced by 1July;
-
No imputation if day, month and year are missing.
Imputed dates will not be displayed in listings except when required.
In the situation where the event date is partial or missing, the date will appear partial or missing 
in the listings, and study day, and any corresponding durations will be presented based on the 
imputations specified in the following paragraphs of this section.
For the analysis of PFS, time-to-first specific AE, overall survival (OS) and any time-to-first 
event, patients not meeting the event will be censored at the first date occurring between:
- the last contact date;
- the end of the applicable phase (if the event is specific to one phase);


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- the cut-off date;
- date of death;
In case of missing PCR assessment, molecular response criteria will be imputed as follows: if 
no value exists in a time-window then the missing value will be imputed as a response if a 
response is observed on the last non-missing previous assessment and on the first next non-
missing assessment (e.g. at Month 4, if a response is observed at the last previous assessment 
(i.e. Month 3) and at the next assessment (Month 5) then a response will be assumed at Month 
4). If assessments are missing on two consecutive time-points, no imputation will be performed. 
For the time-to-first specific AE analysis, patients not meeting the endpoint (=first occurrence 
of CVE) will be censored at the first date occurring between the (last treatment date + 30 days), 
the cut-off date and the date of death. 
2.6
Analysis proportions 
2.6.1
Analysis of Molecular response proportions
The proportion of successful TFR at 12 months, molecular responses or any other proportions 
will be calculated as the number of patients meeting the considered criterion divided by the 
number of patients in the analysis population (analysis populations will be specified in each 
section of this document). 
Simple rates will be calculated by time window looking at all event between the start day and 
the end day of each time window. The number of patients at risk at the start point of time 
window will be used as denominator to compute the percentage of event in each time 
window.
Raw cumulative rates will be presented for each of the following phase:
-
Post-randomization consolidation phase for arm 2 using 1st study drug exposure 
date as starting point and each post-randomization timepoint after as stopping 
point: Day 822 (month 27), Day 913 (month 30), Day 1004 (month 33), Day 1096 
(month 36), checking these stopping timepoint occurred before the start of the TFR 
phase. 
-
TFR phase using the start of TFR phase date as starting point and timepoint 
defined after: Day 30 (1 month), etc… repeat at each-time point every month, Day 
183(month 6), etc… repeat at each-time point every two months, Day 365 (month 
12), etc… repeat at each-time point every three months up to 36 month (Day 
1096) for Arm 1 or up to 24 months (Day 721) for Arm 2 checking these stopping 
timepoint occurred before the start of re-treatment phase. 
-
Re-treatment phase using the start of re-treatment phase date as starting point and 
each timepoint after as stopping point: Day 42 (6 weeks), Day 91 (3 months), 
etc… repeat at each-time point every three months up to 36 months (Day 1096) for 
Arm 1 or up to 24 months (Day 721) for Arm 2.
The denominator to compute the cumulative rate in each phase above will be the number of 
patients in FAS with non missing start date of the phase.


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2.6.2
Analysis of time-to-event endpoints
Time-to-event endpoints will be expressed in months. They will be analyzed using Kaplan-
Meier estimates (product-limit estimates) that will be presented by treatment arm, together with 
a summary of the number (%) of events and censored patients. The associated statistics of the 
time-to-event endpoint will include median, first and third quartiles, and the corresponding two-
sided 95% confidence intervals. Reference time point will be the randomization date + 1 day, 
or the date of entering in TFR phase, or date of entering in re-treatment phase, depending on 
the endpoint of interest. Censoring rules are provided in section 2.5 .
2.6.3
Adjustment for covariates
No covariates are defined in the study protocol. 
2.7
Other definitions
2.7.1
Treatment periods and treatment emergent periods
Per study design, patients are treated during the induction/consolidation phase (up to 24 months 
or 36 months depending on the randomization arm) and may also be treated again during the 
re-treatment phase (up to 36 months). 
On-treatment period is defined from the first nilotinib dose intake up to the last intake of the 
considered phase.
Consequently, two treatment periods will be defined depending on the phase of the study. 
Regarding treatment emergent abnormality or treatment emergent adverse event analysis, the 
treatment emergent period will be defined depending on the phase of the study: 
-
The treatment emergent period during pre-randomization induction/consolidation phase 
(for Arms 1 and 2) is defined as any event occurring between the first study drug dose 
intake, and the minimum date between last study drug dose intake + 30 days and the 
randomization date. 
-
The treatment emergent period during post-randomization consolidation phase (for 
Arm 2) is defined as any event occurring between the randomization date + 1 day and 
the minimum date between last nilotinib dose intake + 30 days and the start of TFR 
phase date. 
-
The treatment emergent period during re-treatment phase is defined as any event 
occurring between the start date of re-treatment phase and the last study drug dose intake 
during the re-treatment phase + 30 days.
2.7.2
TFR phase and emergent adverse events 
The emergent period during TFR phase is defined as the time between last study drug intake 
from (induction/consolidation phase for treatment Arm 1 or last study drug intake from post-
randomization consolidation phase for treatment Arm 2, as described in section 2.8.4) + 1 day 
and end of trial / start of re-treatment.


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All adverse events occurring during the TFR phase will be presented similar to the AEs 
occurring during post-randomization consolidation phase (Arm 2) or re-treatment phase (both 
treatment Arms). Since AEs occurring during TFR phase (i.e. not during treatment), they cannot 
be considered as TEAEs. 
For example, TKI withdrawal syndrome” (e.g. muscle pain) may occur for the first period after 
the treatment discontinuation (i.e. during TFR). Although this Adverse Event technically can 
be considered as “treatment emergent AE”, officially it is not, because the drug is no longer 
taken, so it will be included as an AE of Special Interest during TFR phase. 
2.7.3
Cardiovascular risk factors
Patients will be classified into 4 categories of cardiovascular (CV) risk factors at baseline 
according to the SCORE chart as described below:
1. Very high risk:
Patients with any of the following criteria:
-
At least one documented CV event (CVE) in their medical history as defined with 
the SMQ (Standardized MedDRA Query) and Preferred Term (PT) based on the last 
version of MedDRA associated to the following group of CVEs: CVEs (Ischemic 
heart disease (IHD)), CVEs (Peripheral arterial occlusive disease (PAOD)), CVEs 
(Ischemic cerebrovascular events (ICE)) and others CVEs. These groups will be 
defined based on a Novartis project-related document, the “Compound Case 
Retrieval Strategy” stored in CREDI under path: “Cabinets / CREDI Projects / A / 
AMN107A / Integrated Medical Safety”. The updated version of this document 
effective at the time of the analysis will be used.
-
Diabetes mellitus (type 1 or 2) history, as defined by LLTs based on the last version 
of MedDRA with one or more of the following CV risk factors: smoking history 
(current or ex-smoker), obesity (BMI at baseline>30 kg/m²), hypertension (severe 
or not) or dyslipidemia history (familial or not) as defined by PTs based on the last 
version of MedDRA, micro-albuminuria at baseline (20-200 mg/l)
-
Severe chronic kidney disease, defined as a Glomerular Filtration Rate (GFR) 
<30 ml/min/1.73m² at baseline. GFR is measured by Cockcroft-Gault Creatinine 
Clearance rate as defined below:
GFR = [(140-age)*weight (kg)*0.85 (for women)] / [Cr (umol/l)*0.814]
-
A calculated HeartScore >=10% at baseline as defined by the European Guidelines 
on cardiovascular disease prevention in clinical practice (version 2012) and based 
on age, gender, smoking status, systolic blood pressure, total cholesterol and country. 
2. High risk:
Patients who did not meet any of the “Very high risk” criteria, and with any of the following 
criteria:
-
Medical history of familial dyslipidemia or severe hypertension as defined by PTs 
based on the last version of MedDRA


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-
Diabetes mellitus (type 1 or 2) history as defined by LLTs, with no CV risk factor:
non-smoker, BMI at baseline <=30 kg/m², no history of hypertension, no history of 
dyslipidemia, no micro-albuminuria (for diabetes mellitus patients with a missing 
BMI, missing smoker status or missing micro-albuminuria, the “Very high risk” 
category will be assumed)
-
Moderate chronic kidney disease defined as GFR>=30 ml/min/1.73m² and <=59 
ml/min/1.73m²)
-
A calculated HeartScore >=5% and <10%
3. Moderate risk:
Patients who did not meet any of the “Very high risk” or “High risk” criteria, and with a 
calculated HeartScore >=1% and <5%. 
4. Low risk:
Patients who did not meet any of the “Very high risk”, “High risk” or “Moderate risk” criteria, 
and with a calculated HeartScore <1%. 
If the HeartScore cannot be computed due to missing smoking history, age at baseline, gender, 
country, systolic blood pressure at baseline or total cholesterol at baseline then the CV category 
will be missing, except if other non-missing data classify the patient in the “Very high risk” 
category (i.e. document CVE, diabetes mellitus history with CV risk factor, GFR<30 
ml/min/1.73m²).
If the GFR cannot be computed due to missing age at baseline, weight at baseline or creatinine 
at baseline then the CV category will be missing, except if other non-missing data classify the 
patient in the “Very high risk” category (i.e. document CVE, diabetes mellitus history with CV 
risk factor, HeartScore>=10%).
2.7.4
Study medication
The investigational study drug used during the course of this trial is Nilotinib 300mg BID and 
will be supplied by Novartis for the duration of the trial.
Dosages may be adjusted for a number of reasons, see the protocol for details.
The number of patients who have dose reductions or interruptions, the number of dose 
reductions or interruptions, as well as their reasons, will be summarized. This will be done for 
all reductions or interruptions together and then summarized separately for reductions and for 
interruptions
2.7.5
Duration of exposure
The following algorithm will be used to calculate the duration of nilotinib exposure per study 
phase:

Duration of exposure (months) = (date of last study drug administration – date of first
study drug administration + 1) / 30.4375
The duration includes the periods of temporary interruption. 


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The first administration for the exposure in the induction/consolidation phase is the first study 
drug administration taken from Drug Administration Recorded page of the CRF where daily 
dose administrated is not null/missing.
The last date of exposure in the induction/consolidation phase is defined as date of last study 
drug administration occurring before or on the maximum between:
-
the date of Randomization for Arm1 (date of  visit 9), visit 205 for Arm2 ) 
And 
-
the end of induction/consolidation date (i.e. V400-EOP-ind/con date), including 
subjects Not Randomized.
The first administration of re-treatment phase is defined as first study drug administration 
occurring after or on the maximum date between the end of TFR phase and the 1st visit from re-
treatment visit 301-RT day 1 date.
First study drug administration for Arm 2 post-randomization consolidation phase starts at 
randomization date and ends at the last study drug administration date occurring before or on 
the TFR phase eligibility (i.e. date of visit 205 where eligibility is yes)
These dates of nilotinib administration are taken from Drug Administration Recorded page of 
the CRF where daily dose administrated is not null/missing.
The last date of exposure in the re-treatment phase is the last nilotinib administration of the 
study taken from Drug Administration Recorded (DAR) page of the CRF where daily dose 
administrated is not null/missing.
Duration of exposure will be analyzed separately for Pre-randomization induction/consolidation 
period, post-randomization consolidation period (ARM2) and re-treatment period.
2.7.6
Relative dose intensity 
Relative dose intensity (RDI) is defined as follows: RDI = 100 * DI (mg/day) / PDI (mg/day).
Planned dose intensity (PDI) is the assigned dose by unit of time planned to be given to patients 
as per protocol and is equal to 600 mg/day for nilotinib.
Dose intensity (DI) is defined as follows:

DI (mg/day) = Cumulative dose (mg) / Duration of exposure (day).

For patients who did not take any drug the DI is by definition equal to zero.
Cumulative dose is defined as the total dose taken by the patient during the study treatment 
exposure: 

Cumulative dose (mg) = sum of all rows on the dosage administration record of (actual 
dose * (date of end of medication – date of start of medication + 1) (only ‘+1’ if end 
date not the same as the start date of the next dose)).
Descriptive statistics of RDI as well as RDI by category will be presented. The categories of 
RDI presented will be 0 < 70%, ≥ 70 < 90%, ≥ 90 < 100% and ≥ 100%.


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The average daily dose will also be displayed, is defined as the DI: Cumulative dose (mg) /
(date of end of medication – date of start of medication + 1) (day). 
Note that drug free days are included in the duration of exposure. 
Listing for patients with dose administration records including start/stop dates, total dose and 
frequency, relative dose intensity and Discontinuation/Interruption along with the respective 
reason, will be presented.
2.7.7
Molecular responses

Molecular response 4.5 (MR4.5), defined as either detectable disease ≤0.0032% BCR to 
ABL(IS) ratio or undetectable disease in cDNA with ≥32,000 ABL transcripts. In case 
of undetectable disease, samples with a total of <32,000 ABL transcripts should be 
considered as not evaluable for MR4.5. Not evaluable samples will be classified as non-
responder.

Molecular response 4.0 (MR4.0), defined as either detectable disease ≤ 0.01% BCR to 
ABL(IS) ratio or undetectable disease in cDNA with ≥10,000 ABL transcripts. In case 
of undetectable disease, samples with a total of <10,000 ABL transcripts should be 
considered as not evaluable for MR4.0. Not evaluable samples will be classified as non-
responder.

Major molecular response (MMR), defined as a ≥ 3.0 log reduction in BCR-ABL 
transcripts compared to the standardized baseline or ≤ 0.1% BCR-ABL according to the 
international scale as measured by RQ-PCR.

Relapse during TFR phase
As per protocol, relapse is defined as the loss of MMR, or the confirmed loss of MR4.0 (defined 
by three consecutive tests less than MR4.0 assessed at three consecutive visits according to the 
visit schedule of the TFR phase). If during the three consecutive tests, one of the tests shows 
loss of MMR, this patient will be declared as relapsing and will start the nilotinib re-treatment 
phase immediately even if the definition of confirmed loss of MR4.0 is not yet fulfilled. 
Molecular responses at specific time-windows will be used to define relapse, i.e. the last 
assessment of each time-window will be taken into account (see section Error! Reference 
source not found.). In case of missing data, imputation of PCR assessment will be used as 
described in section 2.5.
2.7.8
Progression-free survival
As per protocol, the progression of disease is defined as follows: 

Progression to accelerated phase (AP): 
-
≥ 15% blasts in peripheral blood or bone marrow aspirate, but <30% blasts in 
both peripheral blood and bone marrow aspirate 
-
≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow aspirate 
-
≥ 20% basophils in peripheral blood 
-
Thrombocytopenia (<100 x 109/L) that is unrelated to therapy


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
Progression to blast crisis (BC): 
-
≥ 30% blasts in peripheral blood or bone marrow aspirate 
-
Appearance of extramedullary involvement other than hepato and/or 
splenomegaly proven by biopsy (i.e. chloroma)
For the purpose of analysis, failure of progression-free survival (PFS) will be defined as the 
earliest occurrence of progression to AP/BC (eCRF captured variable), or death for any cause 
after entering the TFR phase. The date of progression will be defined using the earliest 
assessment date among all criteria. In case of missing assessment date, the End of TFR phase 
visit date will be used. 
If progression to AP/BC (eCRF captured variable) is not observed for the patient, patient will 
be censored as described in section 2.6.
2.7.9
Treatment-free survival
According to the protocol for the purpose of the analysis, failure of treatment free survival 
(TFS), will be defined as the earliest occurrence of progression to AP/BC ((eCRF captured 
variable)), or loss of MMR, or confirmed loss of MR4.0, or re-start of nilotinib treatment for 
any reason, or death for any cause after entering the TFR phase. The date of failure will be 
defined using the earliest assessment date among all criteria. In case of missing assessment date, 
the End of TFR phase visit date will be used. 
If failure of TFS is not observed for the patient, patient will be censored as described in section 
2.6.
2.7.10
Overall survival
As stated in the Protocol, one of the objectives of the CSR analysis is Overall survival, defined 
as the time from randomization to the time of death due to any cause after the date of 
Randomization. For randomized patients not known to have died on or before the cut-off date, 
survival time will be censored, at the date of last contact.
2.7.11
LSC detected cases
LSC detected cases defined for Baseline, as the latest available valid evaluation between 
Screening and Re-screening), derived as follows:
-
“LSC detected” when Ph+ for HIS, or PCR, or both regarding:
  CD34/38 +, or CD34/CD38 –, or Immunophenotypically aberrant CD34+ cells, or  
Immunophenotypically aberrant CD34 negative cells.   
-
“LSC not detected” in all other cases excluding missing and not evaluable observations.
In general:
-
If any of the 8 evaluations is Positive then LSC detected: Yes
-
If there is NO Positive evaluation and at least one evaluation is Negative then LSC 
detected: No
If ALL 8 evaluations are Missing or Not Evaluable then EXCLUDE.


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3.2
Patient disposition and characteristics at screening
3.2.1
Patient disposition
The number of patients treated in induction/consolidation phase will be summarized as 
applicable during the study progress, as well as the number of patients who discontinued the 
induction/consolidation phase, along with the primary reason for discontinuation. 
The summary of patients’ disposition will be presented overall and also by year-phase 
combination: Induction-Consolidation 1st year, Induction-Consolidation 2nd year (pre-
randomization consolidation) and 3rd year of treatment (post-randomization consolidation) for 
ARM 2 patients only.
Number of patients not randomized, along with the respective reason, based on Molecular 
response criteria will be summarized. Considering that the standard criterion was defined as 
having 4 out of 5 quarterly assessments of ≥MR4.0 by a (EUTOS) standardized laboratory 
over the last 12 months AND the last assessment before randomization is at least MR4.0, the 
following categories for Not Randomized patients will be presented:
o
Patient with last assessment < MR4.0
o
Patient with <4 times, out of 5 MR4.0

Patient with 0 out of 5 times MR4.0

Patient with 1 out of 5 times MR4.0

Patient with 2 out of 5 times MR4.0

Patient with 3 out of 5 times MR4.0
o
Patient with 4 out of 5 times MR4.0 but last assessment < MR4.0
o
Patient with <4 times, out of 5 MR4.0 and last assessment MR4.0
o
Other reason not related to Molecular response, including: AE, ICF withdrew, 
PD, lost to follow up, death, etc. 
The following information will also be reported:
Number (percentage) of patients who are:

Randomized

Arm 1 Nilotinib 24-month treatment / Arm 2 Nilotinib 36-month treatment 
o
Patients completed the consolidation phase 
o
Patients discontinued before TFR phase 
o
Patients entered in the TFR phase 
o
Patients who completed the TFR phase * 
o
Patients in the TFR phase with 6 months (i.e. 213 days) without relapse 
o
Patients in the TFR phase with 12 months (i.e. 411 days) without relapse

entering in survival follow-up period 

completing the survival follow-up and the 5 years study period 

completing the survival follow-up before the 5 years study period


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
discontinued from the study without survival follow-up
o
Patients discontinued TFR phase without entering re-treatment phase 

entering in survival follow-up period 

completing the survival follow-up and the 5 years study period 

completing the survival follow-up before the 5 years study period

discontinued from the study without survival follow-up
o
Patients entered in the re-treatment phase
o
Patients discontinued the re-treatment phase

entering in survival follow-up period 

completing the survival follow-up and the 5 years study period 

completing the survival follow-up before the 5 years study period

discontinued from the study without survival follow-up
o
Patients who completed the re-treatment 
*Completion of TFR phase is 36 months for arm 1 and 24 months for arm 2.
The duration of study will be described as: (date of last contact – date of informed consent + 
1)/30.4375. 
Percentages will be computed per arm over the number of patients randomized, over the patients 
entered in TFR phase, over the patient discontinued TFR, over the patient entered in re-
treatment phase or over the patient discontinued the re-treatment phase as mentioned in the TLF 
shells.

Number of patients with no major deviation from protocol, due to which patients are 
excluded from safety or efficacy analysis (for analysis using Per Protocol Set).
Note that for Arm 1 TFR phase can be up to 36 months and re-treatment phase can be up 36 
months, while for Arm 2 TFR phase can be up to 24 months and re-treatment phase can be up 
24 months.
The number of patients in TFR phase at each month before Month 6, at every 2 months from 
Month 6 until Month 12 and every 3 months after Month 12, will be summarized. The number 
of patients in re-treatment phase will also be summarized at Week 6, Month 3 and every 3 
months after. 
A listing of all patients will be provided including the date of enrolment, the date of first and 
last study medication, the date of last contact, did the subject completed the study, discontinued 
the study and reason for discontinuation.
A listing will include details on subjects’ last known date of study medication intake and 
whether the patient is followed up for survival, stem cell transplantation and disease progression 
to AP/BP from study entry and death date if applicable. 


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In addition, for patients participating in the LSC sub-study the following information will also 
be reported:

Number of enrolled patients in the LSC sub-study (signed ICF for LSC sub-study).

Number of enrolled patients in the LSC sub-study who received at least one dose of 
nilotinib 

Number of randomized patients per center and per country
Percentages will be computed over the number of patients enrolled in the in the LSC 
sub-study

Number of randomized patients:

In Arm 1: Percentages will be computed over the number of patients randomized in 
Arm1, as mentioned in the TLF shells.

In Arm 2: Percentages will be computed over the number of patients randomized in 
Arm 2 as mentioned in the TLF shells. Number of patients with no major deviation 
from protocol, due to which patients are excluded from safety or efficacy analysis.
3.2.2
Screen Failures 
Patients not fulfilling inclusion/ exclusion criteria at Baseline (Latest visit between Screening 
and Re-Screening), a table presenting the Reason of Screen failure as specific text presenting 
Inclusion- Exclusion Criteria depending on Protocol version will be created.
A listing presenting all Screen Failures including number and specific text on Inclusion/ 
Exclusion Criteria along with the respective Protocol version number, will be created. 
3.2.3
Study discontinuation
The following information will be reported in the FAS per treatment arm and overall:
Number (percentage) of patients discontinued along with primary reason for discontinuation:

At any time point after randomization

Before entering TFR

After entering the TFR phase

After entering re-treatment phase
A listing of patients who discontinued will be provided per study phase (induction phase, pre-
randomization consolidation phase, post-randomization consolidation phase (arm 2), TFR 
phase and re-treatment phase), including the reason for discontinuation, the date of end of phase, 
the last known date the patient took the treatment, and whether the patient continues to be 
followed for survival. 
A listing of patients relapsing during TFR phase, but not entered immediately or never entered 
re-treatment phase, will be provided.
Study discontinuation and Protocol Deviation Listings will be created.


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3.2.4
Demographics and baseline characteristics variables
Demographics and baseline characteristics will be summarized using the FAS per treatment 
arm, per randomization status (Randomized vs Not Randomized) and overall: 
-
Age at baseline visit in years, both numeric and categorical (<65 & >65)
-
Gender (male, female)
o
If female, child bearing potential (able to bear children, premenarche, post 
menopausal, sterile – of child bearing age)
-
Race (Caucasian, Black, Asian, Native American, North African descent, unknown, 
other)
-
Eastern Cooperative Oncology Group (ECOG) performance status (World Health 
Organization (WHO))
-
BMI (kg/m²) both numeric and categorical (very severely underweight (less than 15.0), 
severely underweight (>15.0 - <16.0), underweight (>16.0 - <18.5), normal (>18.5 -
<25.0), overweight (>25.0 - <30.0), obese class I (>30.0 - <35.0), obese class II (>35.0
- <40.0) and obese class III (>40.0))
-
Smoking history (no, yes, ex-smoker) 
o
If ex-smoker: duration (months) since stopped smoking, calculated as (date of 
screening visit – date stopped smoking + 1) / 30.4375. Imputation of missing or 
partial dates will be handled as described in section 2.5.
o
If yes or ex-smoker, use of tobacco products in the past 1 month (cigarettes, 
cigars, tobacco, other)
-
Family history: presence of family diabetes, hypertension, dyslipidemia, cardiac events, 
cerebrovascular events and peripheral arterial disease. 
Comparison between Randomized and No Randomized group will be done for Demographics 
and baseline characteristics, History of prior Imatinib therapy, Cardiovascular risk factors,
using: Pearson’s Chi-square test p-value, or Fisher’s exact test in case we have one or more 
frequencies in the cross-tabulation MR4.0 Yes/No*Randomized/Not Randomized, less than 5
for categorical variables, to check correlation between MR4.0 and Randomization group.
For numeric variables, Independent t-test for mean (using “Equal” variances or “Unequal” 
variances depending on Variance test result) and Median test for median will be used to test for 
differences between Randomized and Not Randomized group. 
-
Listings will also be provided to display demographic data, as well as family history 
(from eCRF page).


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**Sample pseudo SAS code for Pearson’s and Fisher’s Chi-square test for Categorical 
cross-tabulations*
*Pearson chi-square test;
ods trace on/listing;
ods output ChiSq=pchisq;
proc freq data=DATA;
tables VAR*trtg/ chisq;
run;
ods trace off;
*Keep prob where Statistic="Chi-Square";
*Fisher’s exact test;
ods trace on/listing;
ods output FishersExact=fishert;
proc freq data=DATA;
tables VAR*trtg/ fisher;
run;
ods trace off;
*Keep nValue1 where Name1="XP2 FISH ";
*2 Independent samples t-test ;
ods trace on/listing;
ods output TTests=ttest;
Equality=eqv;proc ttest data=data;
class trtg;
var  age;
run;
ods trace off;
In probf >=0.05 in EQV dataset  then in the ttest keep probt for Variances='Equal';
In probf  <0.05   in EQV dataset  then in the ttest keep probt for Variances='Unequal';
*Median test ;
ods trace on/listing;
ods output MedianTest=medt;
proc npar1way data= data;
class trtg;
var  var;
run;
ods trace off;
*nValue1 where Name1='P2 MED';


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3.2.5
Disease history
Disease History will be described in the FAS per treatment arm and overall as follows:

Time since initial diagnosis (months) calculated as (date of the screening visit – date of 
initial diagnosis) / 30.4375. Imputation of missing or partial dates will be handled as 
described in section 2.6.

Peripheral blood blasts % at diagnosis

PB eosinophils % at diagnosis

PB basophils % at diagnosis

Platelets at diagnosis (109L)

Spleen size at diagnosis (cm)

Extramedullary involvement other than hepato and/or splenomegaly (yes, no)

Sokal score at diagnosis, both continuous and categorical (low risk (<0.8), intermediate 
risk (>0.8-≤1.2) and high risk (>1.2))

Euro (Hasford) score at diagnosis, both continuous and categorical (low risk (≤780), 
intermediate risk (>780-≤ 1480) and high risk (>1480))

EUTOS score at diagnosis, both continuous and categorical (high risk (>87) and low 
risk (≤87))

Previous progression to AP/BP (yes, no)

Attempt to stop treatment with Imatinib (yes, no)

Molecular response at screening (BCR-ABLIS > 1%, BCR-ABLIS > 0.1 - ≤ 1%, > 1%, 
BCR ABLIS > 0.01 - ≤ 0.1%, BCR-ABLIS ≤ 0.01%, Undetectable BCR-ABL)
A listing will also be provided to display disease history.
3.2.6
Medical history/current medical condition
Medical history/current medical condition will be summarized in the FAS per treatment arm 
and overall by MedDRA System Organ Class (SOC) and Preferred Term (PT). A patient will 
be counted only once within a given SOC and within a given PT, even if he had several records. 
A listing will also be provided, including MedDRA SOC and PT, verbatim, date of 
diagnosis/surgery, and whether the condition is still ongoing.
3.2.7
Cardiovascular risk factors
Cardiovascular risk factors will be described with the following categories: very high risk, high 
risk, moderate risk and low risk, per treatment arm and overall. 
Also, based on their medical history, the number and percentage of patients showing the 
following CV risk factors will be described: 
-
CVEs (IHD: Ischemic heart disease) 


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-
CVEs (PAOD: Peripheral arterial occlusive disease), 
-
CVEs (ICE: Ischemic cerebrovascular events)
-
CVEs (Others) 
-
Hypercholesterolemia
-
Hypertension
-
Diabetes
-
At least one CV medical history
In addition, the number and percentage of patients meeting the following criteria based on 
laboratory parameters and vital signs at baseline will be described:
-
Fasting glucose at baseline: 

5.6 – 6.9 mmol/L

>6.9 mmol/L
-
Total cholesterol at baseline (> 5.2 mmol/L)
-
LDL cholesterol at baseline (> 3.3 mmol/L)
-
HDL cholesterol at baseline (< 1.3 mmol/L)
-
Triglycerides at baseline (> 1.7 mmol/L)
-
At least one risk factor between high total cholesterol, high LDL, low HDL, and 
high triglycerides
-
Blood pressure at baseline (systolic blood pressure > 140mmHg or diastolic blood 
pressure > 90 mmHg) by treatment Arm and treatment phase:
Arm1

TFR

Re-treatment phase
Arm2

Post-randomization consolidation phase

TFR

Re-treatment phase
Listing will be provided to display CV risk factors with medical history, laboratory parameters 
and vital signs at baseline.


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3.3
Prior and concomitant medications/non-drug therapies
Prior medications are defined as medications which started and stopped before the date of first 
nilotinib intake. Medications ongoing at the date of first nilotinib intake, as well as medications 
started after the date of first nilotinib intake, are defined as concomitant medications. In addition, 
concomitant medications will be classified by study phase (induction/consolidation, TFR, re-
treatment phases) depending on whether their start dates is before or after the reference start 
dates defined in section 2.5.
-
Prior medication: start date of medication before the date of first nilotinib intake.
-
Concomitant medication during induction/consolidation phase: start date of 
concomitant medication equal or after the date of first nilotinib intake, and 
before the first day of TFR phase.
-
Concomitant medication during TFR phase: start date of concomitant 
medication equal or after the first day of TFR phase and before the end date of 
TFR phase.
-
Concomitant medication during re-treatment phase: start date of concomitant 
medication equal or after the end date of TFR phase (first day of nilotinib
administration in re-treatment phase).
In order to define prior/concomitant medications, missing or partial start and stop dates will be 
imputed as described in section 2.5.
A focus will be given on prior Imatinib, with the history of prior exposure summarized by both 
summary statistics and categorical frequencies (< 2 years, > 2 years - < 5 years, > 5 years). 
Duration of prior Imatinib exposure (months) will be calculated as (end date of prior imatinib 
intake – start date of prior imatinib intake + 1) / 30.4375.
Concomitant medications will be described per treatment arm and overall by therapeutic class 
and PT during induction/consolidation and TFR phase, and during the re-treatment phase in the 
subset of patients entering the re-treatment phase. 
Listings of prior and concomitant medications will be provided, including ATC level 2, PT, 
verbatim, indication, start and stop dates, dose, frequency and route of administration. A 
specific listing will be provided for prior antineoplastic therapies, also including the therapy 
type and reason for discontination of therapy. 
Prohibited medication will be presented in Listings for Full Analysis Set patients, including all 
necessary basci information (Country/Center/ patient number, age/sec/race) and Preferred term, 
ATC level 2 code, Indication, Start/End dates, phase of administratin, route of administration 
along with Dose and Frequency.
3.3.1
Description of CV risk factors based on medical history, laboratory 
parameters and vital signs at baseline
Based on their medical history, the number and percentage of patients showing the following 
CV risk factors will be described per treatment arm and overall: 
-
CVEs (IHD: Ischemic heart disease)


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-
CVEs (PAOD: Peripheral arterial occlusive disease), 
-
CVEs (ICE: Ischemic cerebrovascular events)
-
CVEs (Others) 
-
Hypercholesterolemia
-
Hypertension
-
Diabetes
-
At least one CV medical history
In addition, the number and percentage of patients meeting the following criteria based on 
laboratory parameters and vital signs at baseline will be described:
-
Fasting glucose at baseline: 

5.6 – 6.9 mmol/L

6.9 mmol/L
-
Total cholesterol at baseline (> 5.2 mmol/L)
-
LDL cholesterol at baseline (> 3.3 mmol/L)
-
HDL cholesterol at baseline (<1.3 mmol/L)
-
Triglycerides at baseline (> 1.7 mmol/L)
-
At least one risk factor between high total cholesterol, high LDL, low HDL, and 
high triglycerides
-
Blood pressure at baseline (systolic blood pressure > 140mmHg or diastolic blood 
pressure >90 mmHg)
Listing will be provided to display CV risk factors with medical history, laboratory parameters 
and vital signs at baseline.
3.4
Study medication
During pre-randomization induction/consolidation phase, both treatment arm patients will 
receive nilotinib for 24 months. 
After randomization, there are two phases of the study when patients will take nilotinib:
-
During the consolidation phase for Arm 2 (12 additional months of treatment
before entering TFR phase)
-
During the re-treatment phase in case of relapse during TFR phase (up to 24 or 
36 months of treatment depending on the randomization arm)
The exposure to study medication will be described separately for the 2 above phases by 
treatment arm.


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3.4.1
Duration of exposure
The duration of exposure in months, will be described as a continuous variable and per category 
(< 6, >=6 - <12, >=12 - <18, >=18 - <24, >=24 - <30, >=30 - <36, >=36), by treatment arm and 
phase of study: pre-randomization induction/consolidation phase, consolidation (for Arm 2) and 
re-treatment phase.
3.4.2
Relative dose intensity 
Descriptive statistics of RDI will be presented, as well as RDI categories: 0 < 70%, ≥ 70 < 90%, 
≥ 90 < 100% and ≥ 100%.
The average daily dose will also be displayed, and is defined as the DI: 
DI = Cumulative dose (mg) / (date of end of medication – date of start of medication + 1) (day). 
Drug free days will be included in the duration of exposure. 
3.4.3
Dose reduction and interruption 
The number of dose reductions or interruptions per patient will be summarized using the 
following categories: 0, 1, 2-3, more than 3 reductions/interruptions.
The number of patients with at least one dose reduction/interruption will be summarized, as 
well as the reason for reduction/interruption. 
3.4.4
Dosage administration record
A listing of the dosage administration records in induction/consolidation phase and in re-
treatment phase will be provided, including the dose administered, frequency, start and stop 
dates, whether the dose was changed/interrupted/permanently discontinued and the reason.  
3.5
Protocol deviations
The number of patients with any protocol deviations due to which patients are excluded from 
safety or efficacy analysis will be described in a frequency table based on the Enrolled patients. 
A listing describing the patients with any major protocol deviations due to which patients are 
excluded from safety or efficacy analysis will be provided.
4
Efficacy evaluation
All efficacy analyses will be performed on the set of Full Analysis Set, per treatment arm
(including Not Randomized patients (as applicable) and Randomized as separate columns) and 
overall. 


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4.1
Molecular response
Primary endpoint defined as MR4.0 at 12 months of TFR, will be presented and compared for 
Arm1 vs Arm2, using Pearson’s Chi-square test p-value, or Fisher’s exact test in case we have 
one or more frequencies in the cross-tabulation MR4.0 Yes/No*Randomized/Not Randomized, 
less than 5 for subset of FAS entering the TFR phase, PPS, FAS and PPS.
The cumulative incidence of patients achieving MMR, MR4.0 or MR4.5 at selected time points 
of post-randomization (ARM2 patients) and re-treatment phase, as well as cumulative incidence 
of patients’ loss of MMR, MR4.0 or MR4.5 during TFR phase as described in section 2.7.1 will 
be reported.
Note that for loss of MR4.5 population will be restricted to patients achieving MR4.5 as only 
MMR and MR4.0 are expected to be achieved for all patients eligible for TFR phase.
In addition, the proportions of MMR, MR4.0 and MR4.5 will be described based on time-
windows described in section 2.4 (i.e. the last value of the time-window will be displayed). 
The raw cumulative incidence of response will also be graphically displayed over time.
Listings presenting the BCR-ABL(IS) ratio, the total number of ABL copies, and the molecular 
response(s) for each phase will be provided.
4.2
Subgroup definition 
BCR-ABL (IS) ratio at baseline
The following subgroups will be defined based on the BCR-ABL (IS) levels at Baseline: 
-
BCR-ABL(IS) ratio >1%    
-
BCR-ABL(IS) ratio >0.1% - ≤1%                                                        
-
BCR-ABL(IS) ratio >0.01% - ≤0.1%                                               
-
BCR-ABL(IS) ratio ≤0.01% (0% excluded)                                                         
-
Undetectable BCR-ABL (when BCR-ABL(IS) ratio = 0 and the total number of 
ABL copies>10,000)  
BCR-ABL (IS) ratio at Month 3 
The following subgroups will be defined based on the BCR-ABL (IS) levels at Month 3 (i.e. 
last non missing assessment of the corresponding time-window): 
-
BCR-ABL (IS) ratio at Month 3 <= 0.005% (non missing value lower or equal to 
0.005)
-
BCR-ABL (IS) ratio at Month 3 > 0.005%
Molecular response up to Month 3 (suggested by SSMC members)
The following subgroups will be defined based on the derived molecular response up to
Month 3:
-
Molecular response 4.0 up to Month 3
-
Molecular response 4.5 up to Month 3


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Halving time of BCR-ABL (IS) ratio
The following subgroups will be defined based on the halving time, i.e. the time to reach a 
decrease in BCR-ABL (IS) ratio levels of at least 50% from baseline:
-
Halving time <= 3 months (91 Days)
-
Halving time > 3 months (91 Days)
The halving time will be computed as follows: 
-
Halving time = -d * log(2)/[log(b)-log(a)]
where:
a, is the Baseline BCR-ABL (IS) ratio value
b, is the last Month 3 BCR-ABL (IS) ratio value
d, is the actual treatment time in days over the two measurements
Suboptimal response 
Suboptimal response for patients who prematurely discontinued induction/consolidation phase 
using the following criteria:
-
loss of CHR - n (%)          
-
loss of CCyR - n (%)         
-
loss of MMR - n (%)          
-
no MMR up to Month 24 - n (%)
Will be summarized in tables for Pre-randomization and Post-randomization (ARM2) phase.
Time since initial diagnosis of CML
The following subgroups will be defined based on Time since initial diagnosis of CML:
-
<2 years
-
2 to 4 years
-
4 to 6 years
-
6 to 8 years
-
8 to 10 years
-
10 to 12 years
-
>= 12 years
Sokal risk group
The following subgroups will be defined based on Sokal risk category:
-
Low risk (<0.8)
-
Intermediate risk (>=0.8 - <=1.2)  
-
High risk (>1.2)


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4.3
Kinetics of BCR-ABL(IS) transcript levels
Descriptive statistics of BCR-ABL (IS) ratio will be provided at selected time points based on 
time-windows described in section Error! Reference source not found. (i.e. the last value of 
the time-window will be displayed): 
-
For Pre-randomization phase (Arm1, Arm2): Baseline (Month 0) and every 3 months 
until Month 24.
-
For treatment phase (Arm 2): Month 24 (Randomization), and every 3 months until 
Month 36. 
-
For TFR phase: every month until Month 6, every 2 months until Month 12, and every 
3 months until Month 24 or 36 depending on the randomization arm. This will be 
described per treatment arm and overall.
-
For re-treatment phase: Day 1, Week 6, Month 3 and every 3 months until Month 36. 
This will be described in the subset of patients entering the re-treatment phase.
Listings presenting the BCR-ABL(IS) ratio, the total number of ABL copies, and the molecular 
response(s) will be provided for all patients at each phase. 
4.4
Progression free survival after entering the TFR phase
The evaluation of PFS after entering the TFR phase will be estimated in the two treatment arms 
of the FAS population sub-set entering the TFR phase, using Kaplan-Meier analysis. Summary 
statistics from the Kaplan-Meier distributions will be determined, as well as the proportions of 
patients remaining progression-free at 6, 12, 18, 24, 30 and 36 months after entered the TFR 
phase. The incidence of event will be graphically displayed.
A listing of the assessment of PFS will be provided.
4.5
Treatment free survival after entering the TFR phase
The evaluation of TFS after entering the TFR phase will be estimated in the two treatment arms 
of the FAS population sub-set entering the TFR phase, using Kaplan-Meier analysis. Summary 
statistics from the Kaplan-Meier distributions will be determined, as well as the proportions of 
patients remaining treatment-free at 6, 12, 18, 24, 30 and 36 months after entered the TFR phase. 
The incidence of event will be graphically displayed.
A listing of the assessment of TFS will be provided.
4.6
Overall survival after Randomization 
The evaluation of OS after Randomization will be estimated in the two treatment arms of the 
FAS population sub-set Randomized, using Kaplan-Meier analysis. Summary statistics from 
the Kaplan-Meier distributions will be determined, as well as the proportions of patients 
survived at 6, 12, 18, 24, 30 and 36 months after entered the Randomization. The incidence of 
event will be graphically displayed.
A listing of the assessment of OS will be provided.


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*Sample pseudo SAS code for Kaplan Meier time to Event analysis;
ods listing close;
ods trace on/listing;
ods output  ProductLimitEstimates= timelist1  ;
ods output quartiles=quart;
ods output CensoredSummary=summar;
proc lifetest data=dat method=km ATRISK method=km  outsurv=surv1
timelist=Χ1 Χ2 Χ3 …  alpha=0.05;
  time timev*cens(1) ;
  strata strata/ notest;
run;
ods trace off;
************;
*Sample SAS code for Primary Efficacy;
Please check Pearson’s and Fisher’s exact test in section 3.2.4 
4.7
Other efficacy assessments
Listings of bone marrow analysis, mutational analysis and extramedullary involvement will be 
provided for patients who underwent these assessments during the course of the study. 
Listings presenting the Bone Marrow efficacy related data:  Type of bone marrow sample, 
cellularity, and percent of Blasts, Promyelocytes, Basophilis and Eosinophilis, Number of 
metaphases and additional aberrations for Ph+ and Ph-, for each treatment arm, including Not 
evaluable or Not Done assessments, will be provided.
4.8
SDV sensitivity analysis
In order to assess the impact of patient records-visits with SDV (Source Data Verification)
issues, we have performed a sensitivity analysis, excluding specific records involved in SDV 
issues, for key efficacy and safety outputs. There were 13 patients involved in SDV issues, with 
34 visit-records excluded in total. 
The following Safety-Efficacy results were repeated:
Study completion-discontinuation, summary of TFR and Re-treatment phase, Molecular 
response by visit-time window and cumulatively.  
Hematology and biochemistry, ECG and Echocardiography summaries. Fasting glucose and 
Total cholesterol, Vital signs summaries.


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Survival and Safety follow-up summaries and Listing of Deaths.
5
Pharmacokinetic evaluations
Not applicable.
6
Safety evaluation
Descriptive statistics on AE, laboratory abnormalities, clinically notable ECG, and other safety 
parameters will be presented as separate outputs. The safety summary tables will include only 
assessments collected no later than 30 days after study treatment discontinuation.
Safety analysis will be presented per treatment arm and overall during induction/consolidation 
(between baseline and Month 24 for all patients and between Month 27 and Month 36 for 
patients randomized in Arm 2).  Safety analysis will also be presented per treatment arm and 
overall during TFR in the subset of patients entering TFR phase and re-treatment phase in the 
subset of patients entering re-treatment phase. 
The safety summary tables will only include events occurring during the treatment periods (see 
section 2.7.1), while listings will present all assessments (including those occurring during the 
TFR phase).
6.1
Adverse events
Summary tables will include only TEAEs, i.e. AEs starting or worsening during treatment 
emergent periods and collected no later than 30 days after study treatment discontinuation. AEs 
will be coded using the most recent version of the medical dictionary for regulatory activities 
(MedDRA). 
Frequent TEAEs for pre-randomization period, post Randomization (ARM2) and Re-treatment 
period as well as AEs for TFR period will be summarized in tables. TEAEs, AEs present at 5% 
or more of the Total group of patients will be classified as Frequent.
The incidence and occurrence of TEAEs (all grades and grades 3 or 4) will be summarized by 
SOC and PT, as well as the incidence and occurrence of serious TEAEs regardless of their study 
drug relationship, serious TEAEs suspected to be study drug related, TEAEs leading to study 
drug discontinuation (only for re-treatment phase), and TEAEs requiring dosage adjustment or 
temporarily interruption.


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Frequent TEAEs and AEs (during TFR), considering events with frequency >=5% for one or 
more of the treatment Arms, will be presented for pre-randomization induction/consolidation, 
post randomization consolidation (ARM2), TFR and Re-treatment period. Specifically tables 
will be created presenting: Overall summary, TEAEs/ AEs by system organ class and preferred 
term - overall and maximum grade ¾, Serious Treatment Emergent adverse events regardless 
of study drug relationship by system organ class and preferred term - overall and maximum 
grade ¾. Specific groups of AE of interest will be considered. These are groups of AEs for 
which there is a specific clinical interest in connection with nilotinib treatment and will be 
defined through the use of SMQ and PT based on the last version of MedDRA at the time of 
the analysis. The specific groups to display will be the 4 cardiovascular events (CVEs): CVEs 
(IHD: Ischemic heart disease), CVEs (PAOD: Peripheral arterial occlusive disease), CVEs (ICE: 
Ischemic cerebrovascular events) and CVEs (Others). These groups will be defined based on a 
Novartis project-related document, the “Compound Case Retrieval Strategy” stored in CREDI 
under path: “Cabinets / CREDI Projects / A / AMN107A / Integrated Medical Safety”. The 
updated version of this document effective at the time of the analysis will be used. 
The incidence and occurrence of all grades and grades 3 or 4 of specific TEAEs regardless study 
drug relationship will be summarized by specific group and PT. These tables on specific AEs 
will be displayed for the overall FAS, as well as for the 2 following groups of CV risk factors: 
Very high/High risk; Moderate/Low risk, as well as for each of the CV risk factors separately.
In addition, the time-to-first specific AE (i.e. first occurrence of any of the 4 CVEs defined) 
will be summarized using Kaplan-Meier estimates and Kaplan-Meier plots will be provided. 
Deaths occurring during the treatment emergent period will also be tabulated using SOC and 
PT (only for re-treatment phase). 
All summary tables will be presented separately for pre-randomization induction/consolidation 
phase (between baseline and Month 24 for all patients), for post-randomization consolidation 
phase (between Month 27 and Month 36 for patients randomized in Arm 2), and for re-treatment 
phase. In all incidence summaries, at each level of summarization (specific groups, SOC, and 
PT), patients will only be counted once regardless of how many times the AE occurred, while 
in all occurrence summaries, the number of events will be counted. 
All AE will also be listed, including those collected during the pre-treatment and post-treatment 
period (i.e. later than 30 days after study treatment discontinuation). AE occurring outside of 
the treatment emergent period (during TFR phase) will be flagged and presented separately, 
since they will not be considered as Treatment Emergent Adverse Events. Listings will detail 
the verbatim given by the investigator, PT, abbreviated SOC, start date, end date, duration, 
severity (CTCAE grade), relationship to study drug (not suspected or suspected) and action 
taken (none, dose adjusted, temporarily interrupted, permanently discontinued, concomitant 
medication taken, non-drug therapy given, hospitalization/prolonged hospitalization). The AE 
onset will also be displayed relative (in number of days) to the day of the first dose of study 
medication. This listing will be repeated for the subsets of serious AEs, AESI and AEs leading 
to study drug discontinuation.
“TKI withdrawal syndrome” (muscle pain) will be included in the AESI during TFR phase 
since although related to treatment occurs some days after treatment so it cannot be considered 
as TEAE.


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All deaths will be listed detailing principal cause given by the investigator, PT, date of last dose 
and date of death. Deaths occurring outside the treatment emergent period will be flagged. The 
day of last dose and day of death will also be displayed relative to the day of the first dose of 
study medication. The number of days since last dose (calculated as death day – day of last dose 
+ 1) will also be presented. Also, listing of adverse events leading to study drug discontinuation 
during re-treatment phase for the subset of FAS entering the re-treatment period will be 
presented (suggested by SSMC members).
6.2
Laboratory abnormalities
For laboratory tests covered by the CTCAE version 4.03, the laboratory data will be graded 
accordingly. A Grade 0 will be assigned for all non-missing values not graded as 1 or higher. 
Grade 5 will not be used.
The following hematological parameters will be graded according to the CTCAE criteria: 
WBCs, absolute lymphocytes, absolute neutrophils, hemoglobin and platelets. 
The following hematological parameters will be classified using normal range: eosinophils, 
basophils, monocytes, promyelocytes, myelocytes, metamyelocytes and blast.
The following biochemical parameters will be graded according to the CTCAE criteria: 
bilirubin (total, indirect and direct), aspartate aminotransferase (AST), alanine aminotransferase 
(ALT), sodium (hyper & hypo), potassium (hyper & hypo), calcium (hyper & hypo), 
magnesium (hyper & hypo), glucose (hyper & hypo), creatinine, phosphate (or serum 
phosphorus), lipase, amylase, total cholesterol, triglycerides, alkaline phosphatase (hyper) and 
albumin (hypo).
The following biochemical parameters will be classified using normal range: HDL, LDL, LDH 
and HbA1c.
For bi-directional criteria (calcium, glucose, magnesium, potassium and sodium), hyper and 
hypo abnormalities will be described separately and the value graded in the other direction (e.g. 
hyper if the parameter of interest is hypo) will be counted as a grade 0. 
The following rules will be applied to derive the WBC differential counts when only 
percentages are available (this is important for neutrophils and lymphocytes, as the CTC grading 
is based on the absolute counts).
The method to convert the value is as follows: for each patient, the original laboratory value 
(%) is divided by 100 and multiplied by the WBC count, e.g. for neutrophils (NEU): 
NEU count = (WBC count) * (NEU %value / 100)
In order to derive the corresponding absolute normal range, the rule to be applied depends on 
the availability of the % range and the absolute range for the differential:

If the % range is missing and the absolute range is missing, then the pre-defined normal 
range as reported in the Merck manual (see Novartis business guidance FRM-0015557 
- Laboratory value references) will be used.


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
If the absolute range is NOT missing (% range is or isn’t missing), then the absolute 
range provided by the site will be used. 

If the % range is NOT missing and the absolute range is missing, then the % normal 
limits (i.e. lower limit normal (LLN) and upper limit normal (ULN)) are divided by 100 
and multiplied by the corresponding normal limits of WBC count, e.g. for NEU:
-
LLN for NEU count = (LLN for WBC count) * (LLN for NEU % value/ 100)
-
ULN for NEU count = (ULN for WBC count) * (ULN for NEU % value/ 100)
Shift tables using CTCAE grades will be produced for hematology and biochemistry separately 
to compare:

baseline (of induction/consolidation phase) and the worst on-treatment value during 
post-randomization consolidation phase (see baseline definitions in section 2.4)

baseline RT and the worst on-treatment value during re-treatment phase (see baseline 
definitions in section 2.5.3).
Percentages will be calculated using the number of available patients at baseline/baseline RT 
with corresponding grade and at least one non-missing on-treatment value as the denominator.
Additionally, shift tables between baseline (of induction/consolidation phase) and the worst 
value during the whole study period (including TFR phase) will be presented.
For laboratory tests where CTCAE grades are not defined, shift tables using the 
low/normal/high/(low and high) classification will be produced to compare baseline/baseline 
RT to the worst on-treatment value during respectively induction/consolidation phase and re-
treatment phase. Percentages will be calculated using the number of available patients at 
baseline/baseline RT with corresponding classification and at least one non-missing on-
treatment value as the denominator.
In addition, descriptive statistics will be provided for all laboratory parameters at each planned 
visit of the induction/consolidation phase, per treatment arm and overall, and at each planned 
visit of the re-treatment phase in the subset of FAS entering re-treatment phase. 
Listings of hematology and biochemistry laboratory values and normal ranges will be provided, 
including the sample date/study day, test, SI unit (unit as reported by the site), value, low/high 
ranges. Grades will also be listed when CTCAE grades are defined.
6.3
Vital signs 
Vital signs including Height and Weight for Baseline, Body temperature, Sitting pulse and 
Sitting BP Systolic/Diastolic by visit, will be summarized in tables and will be presented in 
detailed Listing.


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6.4
Electrocardiograms (ECGs)
Overall ECG interpretation and details of abnormalities are collected at Screening and selected 
visits. The ECG QTcF result (msec) at each visit will be categorized (≤450, >450 -≤480, >480 
– ≤500, >500 and missing). Shift tables will display the categorized ECG QTcF result at 
baseline/baseline RT compared to the worst on-treatment value during respectively 
induction/consolidation phase and re-treatment phase. 
A shift table displaying the baseline categorized ECG QTcF result compared with the worst 
post-baseline categorized result will be produced. Percentages will be calculated using the 
number of patients with that categorized result at baseline as the denominator.
The number of patients recording notable ECG QTcF increases (Increase from baseline > 30/ 
Increase from baseline > 60) from baseline/baseline RT at least once during the trial will also 
be presented. Percentages will be calculated using the number of patients with both 
baseline/baseline RT and post baseline/baseline RT evaluations.
A listing will be provided including the date of ECG, QTcF interval, and whether there is a 
clinically significant abnormality
6.5
Echocardiography (cardiac imaging)
As per protocol, echocardiography is performed at screening and may be repeated at the 
investigator’s discretion if there are signs or symptoms of cardiotoxicity.
Baseline LVEF data will be descriptively analyzed, together with the overall interpretation 
(normal, clinically insignificant abnormality, clinically significant abnormality). A shift table 
displaying the baseline overall interpretation compared with the worst post-baseline overall 
interpretation will be produced. Percentages will be calculated using the number of patients 
with that overall interpretation at baseline as the denominator.
6.6
Survival Follow-up
Survival follow-up records will be summarized in a table by FU visit, presenting frequency as 
number and percentage of alive patients, Cases of stem cell transplantation, Progression of 
disease to AP/BP, administration of TKI treatment and drug category (Nilotinib, Imatinib, 
Other) if yes.
Time window for Survival follow-up defined in section 2.5.1.
A listing will be provided presenting for each visit: subject status (alive yes /no), if no date of 
death and principal cause of death along with specific details in case of other cause. If subject 
alive or lost to follow-up last date of contact will be presented. Information regarding stem cell 
transplantation, Progression of disease to AP/BP, administration of TKI treatment and drug 
category (Nilotinib, Imatinib, Other) if yes, along with specific details for treatment in case of 
other than standard categories.


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6.7
Safety Follow-up
Safety follow-up information will be summarized in a table of frequency as number and 
percentage, including: type of follow-up (clinical visit, telephone call), as well as if Medical 
intervention was considered necessary.
A listing will be provided including all relevant information collected in the CRF: 
If follow-up happened, if no reason for no safety follow-up, if yes, type of follow-up (clinical 
visit, telephone call), along with the respective date. If Medical intervention was considered 
necessary and date of Medical intervention.
6.8
LSC sub-study analysis
Apart from selected parts of the main study analysis that will be repeated for patients 
participating in the LSC sub-study in addition will be presented:
Descriptive Statistics for Baseline, Months 24, 36, EOP TFR as well as for change from baseline 
for:
-
CD34 cells as Total percentage.
-
CD34+/CD38+ cells Percentage from total CD34+ cells.
-
Descriptive Statistics for number of events sorted in CD34+/CD38+ cells
Then proportion and descriptive statistics tables for patients with presence of Ph+ LSC in bone 
marrow, in terms of in CD34+/CD38+, CD34+/CD38-, Immunophenotypically aberrant 
CD34+ and Immunophenotypically aberrant CD34 negative cells as:
-
Ph+ by HIS status, 
-
Descriptive statistics of Ph+ in CD34+/CD38+ cells
-
BCR-ABL by RT-PCR status, in CD34+/CD38+ cells
Specifically:
-
Percentage from total CD34+ cells, CD34+/CD38+ cells.
-
Percentage from total CD34+ cells, CD34+/CD38- cells.
-
Percentage from total CD34+ cells.
-
Percentage from total CD34+ cells.
-
Percentage of Ph+ cells, CD34+/CD38+ cells.
-
Percentage of Ph+ cells, CD34+/CD38- cells.
-
Percentage of Ph+ cells, Immunophenotypically aberrant CD34+ cells.
-
Percentage of Ph+ cells, Immunophenotypically aberrant CD34 negative cells.
-
Total Percentage of CD34+ cells.


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Frequency and descriptive statistics tables will be created for the above endpoints, along with 
Listings presenting individual data.
For the 24/36 month data analysis for the Leukemic Stem Cell sub-study of the 
CAMN107AIC05 clinical trial, additional analysis will be performed for publication purposes.
Prior Imatinib exposure before screening (<5 vs >=5 years), Major Molecular Response (MMR 
Yes vs No), Age (<65 vs >=60 years) and Sokal score (Low, Intermediate, High risk) by LSC 
category at Baseline, will be presented for Not Randomized and Randomized patients in a 
summary table.
Tables summarizing descriptive statistics of LSC cells for Baseline, Month 24 as well as the 
change from Baseline to Month 24, will be presented for Arm1, Arm2, Not Randomized, 
Randomized (Arm1 and Arm2) and Total (Randomized and Not Randomized), for LSC 
detected subjects.
A table presenting number and percentage of subjects using separate columns for Arm1, Arm2, 
Not Randomized, Randomized (Arm1 and Arm2) and Total (Randomized and Not 
Randomized), at Baseline, Month 24, Month 36 (for Arm 2 subjects only) and EOP TFR will 
be created.
In addition, individual figures for HIS and PCR detected patients, presenting number of sorted 
events for each patient by visit (Baseline, Month 24, Month 36 for ARM2 patients only and 
EOP TFR), will be provided. Separate figures for each one of the 4 basic cell categories will 
be presented:

CD34+ / CD38 +

CD34+ / CD38-

Immunophenotypically aberrant CD34+

Immunophenotypically aberrant CD34-
Summary figures will be created, presenting number and percentage of patients with positive 
result by HIS and PCR by visit (Baseline, Month 24, Month 36 for ARM2 patients only and 
EOP TFR) for :

CD34+ / CD38 +

CD34+ / CD38-

Immunophenotypically aberrant CD34+

Immunophenotypically aberrant CD34-
Number of patients with detectable LSC – LSC sub study for LSCFAS will be presented by 
bar diagram for publication purpose.
7
Other topics 
No other topics will be studied.
8
Sample size calculation
According to the protocol amendment 2, it is expected that approximately 565 patients from 
approximately 300 centers will be recruited into this study.


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This sample size calculation has been based on an estimation of the difference in the percentage 
of patients relapsing during the 12-month TFR phase of the study between the two treatment 
arms. Further details are given in the study protocol.
9
References
Protocol AMN107AIC05, version 04 (including Amendment 4); 01 Jun 2016.
Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, US Department of 
Health and Human Services, National Institutes of Health, National Cancer Institute, NIH 
Publication No. 09-5410, published on May 28, 2009 (v4.03: June 14, 2010)
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE 4.03 2010-06-14 QuickReference 5x7.pdf
Merck Manual of Therapeutics, Normal Laboratory Values; FRM-0015557 v 3.0.
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). 
European Heart Journal (2012) 33, 1635–1701




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Document History – Changes compared to previous version of RAP 
module 7.1
Version
Date
Changes
1.0
08-Jan-2020
First Draft 
1.1
10-Feb-2020
Updated version, added LSC substudy ouputs
1.2
05-Mar-2020
Revised version
1.3
20-Mar-2020
Updated version after tema review
1.4
23-Apr-2020
Updated tables with PPS outputs, added LSC extra analysis
1.5
17-Jun-2020
Updated according to DR1 findings
1.6
31-Aug-2020
Updated according to DR2 findings
1.7
22-Sep-2020
Updated according to Final Run requirements
1.8
06-Oct-2020
Added SSMC requested outputs
Pre-Final
07-Oct-2020
Finalize document
Final
09-Oct-2020
Minor cosmetics update and final version for CSR
Addendum
18-Jan-2021
Sensitivity analysis, repeat key outputs excluding SDV(not done)
involved visits , footnotes updated for populations as per module 3, 
Updated KM TLFs for progression to AP/BC (eCRF captured 
variable) for PFS and TFS. In text tables footnotes are shortned in 
outputs.Table numbers are updated for following :
T14.2-4.2.1.1 to T14.2-4.2.11, T14.3-1.1.2.1 to T14.3-1.1.21, 
T14.3-1.1.2.2 to T14.3-1.1.22,
Figure numbers are updated for following:
F14.2-2.3.1.1 to F14.2-2.3.11, F14.2-2.5.1.1 to F14.2-2.5.11
Cut off date in TLFs footnotes replaced by DBL date
Minor updates in title and footnote as per CSR final run review 
comments.
Addendum 
V1.1
29-Jan-2021
Excluding Safety SDV analysis outputs as they were not affected by 
the SDV record exclusion of specific visits, since they are based on 
Start and Stop dates independently of standard study visits.
Tables 14.3-1.1.4 and 14.3-2.4, 14.3-3.4, 14.3-4.5 and 14.3-4.6 for 
Duration of exposure, Relative dose intension, Dose reduction, 
Concomitant medication during TFR and Re-treatment.
Tables 14.3.1-1.5, 14.3.1- 3.3.3, 14.3.1-4.3.3, 14.3.1-4.4.3
14.3.1-4.8.3, 14.3.1-5.3.3, 14.3.1-6.3.3, 14.3.1-6.6.3, 14.3.1-6.7.3, 
14.3.1-7.3.3, 14.3.1-7.4.3, 14.3.1-7.7.3, 14.3.1-7.8.3    for AEs and 
TEAEs.
Table 14.3.1-9.4 for On treatment deaths.
Tables 14.3.1-10.3.3,  14.3.1-10.4.3, 14.3.1-10.7, 14.3.1-10.8 and 
14.3.1-11.3  for CVEs.
Table 14.3.1-12.2 for Medical History.
Figures 14.3.1-1.5 and 1.6 for Time to CVE.
Addendum 
V1.2
09-Mar-2021
Adding footnote for patient #
 in
Tables: 10-2,14.1-2.1, 14.1-2.5, 14.1-2.6, 14.1-2.6.1,  
12-1, 14.3.1-1.1,14.3.1-2.1, 14.3.1-3.1.1, 14.3.1-3.1.2,14.3.1-3.5.1, 
14.3.1-4.1.1, 14.3.1-4.1.2, 14.3.1-4.6.1, 14.3.1.-4.6.2
12-17, 14.3.1-5.1.1, 14.3.1-5.1.2, 14.3.1-6.1.1, 14.3.1-6.1.2     
Listings: 14.3.2-2.2, 16.2.7-1.1, 16.2.7-2.2, 16.2.1-1.1, 16.2.1-1.2, 
16.2.5-1.1


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Version
Date
Changes
Adding footnote for patient 
 in tables: 12-1, 12-9
14.3.1-1.1, 14.3.1-1.2, 14.3.1-2.1, 14.3.1-3.1.1, 14.3.1-3.1.2,
14.3.1-4.1.1, 14.3.1-4.1.2, 14.3.1-4.6.1, 14.3.1-4.6.2, 14.3.1-6.1.1, 
14.3.1-6.1.2
Listings: 16.2.7-1.1, 16.2.7-2.1
Addendum 
V1.3
20-Apr-2021
Adding footnote for patient #
 in tables:  12-1, 12-9, 12-
17
14.3.1-1.1, 14.3.1-1.2, 14.3.1-2.1, 14.3.1-3.1.1, 14.3.1-3.1.2,
14.3.1-4.1.1, 14.3.1-4.1.2, 14.3.1-4.6.1, 14.3.1-4.6.2, 14.3.1-5.1.1, 
14.3.1-5.1.2,14.3.1-6.1.1, 14.3.1-6.1.2
Listings: 14.3.2-2.2, 16.2.7-1.1, 16.2.7-2.1, 16.2.7-2.2
Adding footnote for patient #
 in tables:
14.1-2.2, 14.1-2.5, 14.1-2.6 and 14.1-2.6.1
Addendum 
V1.4
06-May-2021
Adding Listing 16.1.7-1.1 Randomization schemes on Randomized 
patients
Addendum 2 
06-May-2021
Final version


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Table of contents
Document History – Changes compared to previous version of RAP module 7.1 ....................2
1.
General guidance...............................................................................................................38
1.1
Document headers .................................................................................................38
1.2
Rules of presentation .............................................................................................38
1.3
Document headers .................................................................................................39
1.4
Presentation of table numbering and titles within this document..........................40
1.5
Treatment group labels and ordering.....................................................................40
1.6
Distribution logistics..............................................................................................40
2.
Overall table of contents for statistics and programming output ......................................41
Tables, Listing Figures .............................................................................................................41
3.
Shells and specification for CSR.......................................................................................75
3.1
Shells and specifications for sections 10 of the CSR (In-textText tables, 
listings and figures)................................................................................................75
Section 10........................................................................................................................109
Table 10-1 Analysis sets – All patients...........................................................................109
Table 10-2 Patient disposition during Induction/Consolidation phase and post-
Randomization Consolidation phase -Enrolled patients......................................110
Table 10-3 Demographic and characteristics at baseline – Full Analysis Set.................111
Table 10-4 Disease history – Full Analysis Set...............................................................113
Table 10-5 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation Safety Set .....................................................................116
Table 10-6 Duration of exposure to study treatment during post-randomization 
Consolidation phase (ARM 2) - Subset of Safety Set randomized to Arm 2......116
Table 11-1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................117
Table 11-2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................117
Table 11-3 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................117
Table 11-4 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................118
Table 11-5 Primary endpoint, Molecular response MR4.0 at 12 months of TFR 
phase–Subset of Full Analysis Set entering the TFR phase ................................118
Table 11-6 Secondary endpoint Kaplan-Meier analysis of treatment-free survival 
during the TFR phase – Subset of Full Analysis Set entering the TFR phase.....119
Table 11-7 Secondary endpoint, Molecular response 4.0 during post-randomization 
consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................120
Table 11-8 Secondary endpoint, Kaplan-Meier analysis of overall survival from 
Randomization–Randomized Set.........................................................................121


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Table 12-1 Overall summary of treatment-emergent adverse events occurring during 
pre-randomization Induction/consolidation phase – Full Analysis Set...............122
Table 12-2 Overall summary of treatment-emergent adverse events occurring during 
post-randomization consolidation phase (ARM 2) – Subset of Full Analysis 
Set randomized to Arm 2.....................................................................................123
Table 12-3 Overall summary of treatment-emergent adverse events occurring during 
re-treatment phase – Subset of Full Analysis Set entering the re-treatment 
phase ....................................................................................................................124
Table 12-4 Overall summary of adverse events occurring during TFR phase – Subset 
of Full Analysis Set entering the TFR phase.......................................................125
Table 12-5
Overall summary of frequent [1] treatment-emergent adverse 
events occurring during pre-randomization Induction/consolidation phase –
Full Analysis Set..................................................................................................126
Table 12-6 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during post-randomization Consolidation phase (ARM 2) – Subset 
of Full Analysis Set randomized to Arm 2..........................................................126
Table 12-7 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during re-treatment phase – Subset of Full Analysis Set entering 
the re-treatment phase..........................................................................................126
Table 12-8 Overall summary of frequent [1] adverse events occurring during TFR 
phase – Subset of Full Analysis Set entering the TFR phase ..............................126
Table 12-9 Serious treatment-emergent adverse events incidence, regardless of study 
drug relationship, by system organ class and preferred term during pre-
randomization Induction/consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................127
Table 12-10 Serious treatment-emergent adverse events incidence, regardless of 
study drug relationship, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................128
Table 12-11 Serious treatment-emergent adverse events incidence, regardless of 
study drug relationship, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................128
Table 12-12 Serious adverse events incidence, regardless of study drug relationship, 
by system organ class and preferred term during TFR phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase.......128
Table 12-13 Treatment-emergent adverse events of interest incidence, regardless of 
study drug relationship, by specific group and preferred term during Pre-
randomization Induction/consolidation phase –by treatment arm, overall and 
maximum grade 3/4 – Full Analysis Set..............................................................129
Table 12-14 Treatment-emergent adverse events of interest incidence by specific 
group and preferred term during post-randomization Consolidation phase 
(ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis Set 
randomized to Arm 2...........................................................................................130


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Table 12-15 Treatment-emergent adverse events of interest incidence by specific 
group and preferred term during re-treatment phase – overall and maximum 
grade 3/4 – Subset of Full Analysis Set entering the re-treatment phase............131
Table 12-16 Adverse events of interest incidence by specific group and preferred 
term during TFR phase – overall and maximum grade 3/4 – Subset of Full 
Analysis Set entering the TFR phase...................................................................131
Table 12-17 Treatment-emergent adverse events incidence leading to study drug 
discontinuation by system organ class and preferred term during pre-
randomization Induction/Consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................132
Table 12-18 Treatment-emergent adverse events incidence leading to study drug 
discontinuation by system organ class and preferred term during post-
randomizationphase (ARM 2) – overall and maximum grade 3/4 – Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................133
Table 12-19 On treatment deaths, by system organ class and preferred term during 
pre-randomization Induction/Consolidation phase - Safety Set ..........................133
Table 12-20 On treatment deaths, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – Subset of Safety Set 
randomized to Arm 2...........................................................................................134
Table 12-21 On treatment deaths, by system organ class and preferred term during 
re-treatment phase – Subset of Safety Set entering the re-treatment phase.........134
Listing 12-1 Listing of deaths – Full Analysis Set..........................................................135
Figure 11-1 Primary endpoint, Bar plot MR4.0 at 12 months of TFR phase –Subset 
of Full Analysis Set entering the TFR phase.......................................................136
Figure 11-2 Kaplan-Meier analysis of treatment-free survival during the TFR phase 
–Subset of Full Analysis Set entering the TFR phase .........................................137
3.2
Shells and specifications for Sections 14 and 16 of the CSR..............................138
Section 14 – tables, figures and graphs referred to but not included in the text .............138
Section 14.1 – Demographic data....................................................................................138
Table 14.1-1.1 Enrollment by country and center – All patients ....................................139
Table 14.1-1.2 Randomization by country and center – Randomized patients...............140
Table 14.1-1.3
Patient disposition (Screening failures), All patients..........................141
Table 14.1-2.1 Patient disposition during Induction/Consolidation phase and post-
Randomization Consolidation phase -Enrolled patients......................................143
Table 14.1-2.2 Patient disposition in each randomized arm – Full Analysis Set............144
Table 14.1-2.2.1 Patient disposition – Enrolled patients in LSC substudy.....................147
Table 14.1-2.3 Analysis sets –All patients......................................................................148
Table 14.1-2.4 Not Randomized patients - Enrolled patients .........................................149
Table 14.1-2.5   Patient disposition, Overall and by year-phase -Enrolled patients .......150
Table 14.1-2.6 Patients discontinued and reason for discontinuation – Full Analysis 
Set ........................................................................................................................154
Table 14.1-2.6.1 Patients discontinued and reason for discontinuation, SDV 
sensitivity – Full Analysis Set .............................................................................156


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Table 14.1-2.7 Summary of TFR phase – Full Analysis Set...........................................157
Table 14.1-2.7.1 Summary of TFR phase, SDV sensitivity – Full Analysis Set ............158
Table 14.1-2.8    Summary of re-treatment phase – Full Analysis Set............................159
Table 14.1-2.8.1 Summary of re-treatment phase, SDV sensitivity – Full Analysis 
Set ........................................................................................................................160
Table 14.1-2.9 Summary of patients with relapse during the TFR phase but no 
entering re-treatment phase –-Subset of Full Analysis Set entering the TFR 
phase ....................................................................................................................161
Table 14.1-3.1 Demographic and characteristics at baseline– Full Analysis Set............163
Table 14.1-3.1.1 Demographic and characteristics at baseline– LSC sub-study Full 
Analysis Set .........................................................................................................166
Table 14.1-4.1 Disease history – Full Analysis Set.........................................................167
Table 14.1-4.1.1 Disease history – LSC sub-study Full Analysis Set.............................170
Table 14.1-5.1 History of prior Imatinib therapy – Full Analysis Set ............................171
Table 14.1-5.1.1 History of prior Imatinib therapy – LSC sub-study Full Analysis Set.172
Table 14.1-5.2 Prior antineoplastic therapy, other than Imatinib, by ATC class and 
preferred term -  Full Analysis Set ......................................................................173
Table 14.1-6.1 Cardiovascular risk factors at baseline – Full Analysis Set....................174
Table 14.1-6.2 Cardiovascular risk factors (based on medical history, laboratory 
values and vital signs at baseline) – Full Analysis Set........................................175
Section 14.2 – Efficacy and other non-safety data (e.g. PK, PK/PD, Health Econ., 
QoL).....................................................................................................................177
Figure 14.2-1.1 Box-plot of BCR-ABL ratio (IS) during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................178
Figure 14.2-1.2 Box-plot of BCR-ABL ratio (IS) during post-randomization 
Consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
ARM 2 .................................................................................................................179
Figure 14.2-1.3 Box-plot of BCR-ABL ratio (IS) during TFR phase – Subset of Full 
Analysis Set entered TFR....................................................................................179
Figure 14.2-1.4 Box-plot of BCR-ABL ratio (IS) during re-treatment phase – Subset 
of Full Analysis Set entered re-treatment ............................................................179
Figure 14.2-1.5 Box-plot of BCR-ABL ratio (IS) during TFR phase – , SDV 
sensitivity Subset of Full Analysis Set entered TFR ..........................................180
Figure 14.2-1.6 Box-plot of BCR-ABL ratio (IS) during re-treatment phase, SDV 
sensitivity –Subset of Full Analysis Set entered re-treatment............................180
Figure 14.2-2.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase - Full Analysis Set .............................................181
Figure 14.2-2.1.2 Raw cumulative incidence of MMR during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
ARM 2 .................................................................................................................181
Figure 14.2-2.2.1 Raw cumulative incidence of MMR during pre-randomization
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio - Full 
Analysis Set .........................................................................................................182


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Figure 14.2-2.2.2 Raw cumulative incidence of MMR during post-randomization 
Consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to ARM 2.............................................182
Figure 14.2-2.3.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................183
Figure 14.2-2.3.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
ARM 2 .................................................................................................................183
Figure 14.2-2.3.11 Raw cumulative incidence of MR 4.0, Randomized vs Not 
Randomized, during pre-randomization Induction/Consolidation phase - Full 
Analysis Set .........................................................................................................184
Figure 14.2-2.4.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio - Full 
Analysis Set .........................................................................................................184
Figure 14.2-2.4.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to ARM 2.............................................185
Figure 14.2-2.5.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set .............................................185
Figure 14.2-2.5.11 Raw cumulative incidence of MR 4.5, Randomized vs Not 
Randomized, during pre-randomization Induction/Consolidation phase- Full 
Analysis Set .........................................................................................................185
Figure 14.2-2.5.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
ARM 2 .................................................................................................................185
Figure 14.2-2.6.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio - Full 
Analysis Set .........................................................................................................185
Figure 14.2-2.6.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to ARM 2.............................................186
Figure 14.2-2.7.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline..................................................................................................186
Figure 14.2-2.8.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching MR 
4.0 at baseline ......................................................................................................186
Figure 14.2-2.9.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching MR 
4.5 at baseline ......................................................................................................186
Figure 14.2-2.9.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Induction/Consolidation phase (ARM 2)- Subset of Full Analysis Set patients 
not reaching MR 4.5 at baseline, randomized to ARM 2....................................186
Figure 14.2-2.10.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set .........................................................................................................187


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Figure 14.2-2.10.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) by BCR-ABL(IS) ratio at baseline - Subset of 
Full Analysis Set randomized to ARM 2.............................................................187
Figure 14.2-2.11.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set .........................................................................................................188
Figure 14.2-2.11.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) by BCR-ABL(IS) ratio at baseline - Subset of 
Full Analysis Set randomized to ARM 2.............................................................188
Figure 14.2-2.12.1 Box-plot of BCR-ABL ratio (IS) during pre-randomization 
Induction/Consolidation phase, excluding outliers (BCR-ABL (IS) ratio>10 -
Full Analysis Set..................................................................................................189
Figure 14.2-2.12.2 Box-plot of BCR-ABL ratio (IS) over post-randomization 
Consolidation phase (ARM 2), excluding outliers (BCR-ABL (IS) ratio>10 -
Subset of Full Analysis Set randomized to ARM 2.............................................189
Figure 14.2-13.1 Raw cumulative incidence of loss of MMR during TFR – Subset of 
Full Analysis Set entering the TFR phase ...........................................................191
Figure 14.2-13.2 Raw cumulative incidence of MMR during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................191
Figure 14.2-13.3 Raw cumulative incidence of loss of MMR during TFR, SDV 
sensitivity – Subset of Full Analysis Set entering the TFR phase.......................192
Figure 14.2-13.4 Raw cumulative incidence of MMR during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase..192
Figure 14.2-14.1 Raw cumulative incidence of loss of MR4.0 during TFR phase –
Subset of Full Analysis Set entering the TFR phase ...........................................192
Figure 14.2-14.2 Raw cumulative incidence of MR4.0 during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................192
Figure 14.2-14.3 Raw cumulative incidence of loss of MR4.0 during TFR phase, 
SDV sensitivity –Subset of Full Analysis Set entering the TFR phase...............193
Figure 14.2-14.4 Raw cumulative incidence of MR4.0 during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase..193
Figure 14.2-15.1 Raw cumulative incidence of loss of MR4.5 during TFR phase –
Subset of Full Analysis Set entering the TFR phase with MR4.5.......................193
Figure 14.2-15.2 Raw cumulative incidence of MR4.5 during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................193
Figure 14.2-15.3 Raw cumulative incidence of loss of MR4.5 during TFR phase, 
SDV sensitivity – Subset of Full Analysis Set entering the TFR phase with 
MR4.5..................................................................................................................194
Figure 14.2-15.4 Raw cumulative incidence of MR4.5 during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase..194
Figure 14.2-16 Bar plot MR4.0 at 12 months of TFR phase –Subset of Full Analysis 
Set entering the TFR phase..................................................................................195
Figure 14.2-16.2 Bar plot MR4.0 at month 12 TFR phase , SDV sensitivity –Subset 
of Full Analysis Set entering the TFR phase.......................................................195


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Figure 14.2-17.1 Kaplan-Meier analysis of progression-free survival during the TFR 
phase –Subset of Full Analysis Set entering the TFR phase ...............................196
Figure 14.2-17.2 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase –Subset of Full Analysis Set entering the TFR phase ...............................196
Figure 14.2-17.3 Kaplan-Meier analysis of progression-free survival during the TFR 
phase, SDV sensitivity –Subset of Full Analysis Set entering the TFR phase....197
Figure 14.2-17.4 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase, SDV sensitivity –Subset of Full Analysis Set entering the TFR phase....197
Figure 14.2-18.1 Kaplan-Meier analysis of reachievement of MMR, after loss of 
response in TFR –Subset of Full Analysis Set entering the re-treatment phase..197
Figure 14.2-18.2 Kaplan-Meier analysis of reachievement of MR4.0, after loss of 
response in TFR – Subset of Full Analysis Set entering the re-treatment phase.197
Figure 14.2-18.3 Kaplan-Meier analysis of reachievement of MMR, after loss of 
response in TFR, SDV sensitivity –Subset of Full Analysis Set entering the 
re-treatment phase................................................................................................198
Figure 14.2-18.4 Kaplan-Meier analysis of reachievement of MR4.0, after loss of 
response in TFR, SDV sensitivity – Subset of Full Analysis Set entering the 
re-treatment phase................................................................................................198
Table 14.2-1.1 Description of BCR-ABL (IS) ratio at Month 3 and halving time of 
BCR-ABL (IS) ratio subgroups – Full Analysis Set ...........................................199
Table 14.2-2.1.1 Molecular response MR4.0 at 12 months of TFR–Subset of Full 
Analysis Set entering the TFR phase...................................................................200
Table 14.2-2.1.2 Molecular response MR4.0 at 12 months of TFR–Subset of Per 
Protocol Analysis Set entering the TFR phase ....................................................200
Table 14.2-2.1.3 Molecular response MR4.0 at 12 months of TFR–Full Analysis Set ..201
Table 14.2-2.1.4 Molecular response MR4.0 at 12 months of TFR–Per Protocol 
Analysis Set .........................................................................................................201
Table 14.2-2.1.5 Molecular response MR4.0 at 12 months of TFR– Subset of Full 
Analysis Set entering the TFR phase with MR4.0 achieved up to month 3 of 
pre-randomization Induction/Consolidation phase..............................................202
Table 14.2-2.1.6 Molecular response MR4.0 at 12 months of TFR– Subset of Full 
Analysis Set entering the TFR phase with MR4.5 achieved up to month 3 of 
pre-randomization Induction/Consolidation phase..............................................202
Table 14.2-2.1.7 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –
Subset of Full Analysis Set entering the TFR phase ...........................................202
Table 14.2-2.1.8 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –
Subset of Per Protocol Analysis Set entering the TFR phase..............................202
Table 14.2-2.1.9 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –
Full Analysis Set..................................................................................................202
Table 14.2-2.1.10 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity 
–Per Protocol Analysis Set ..................................................................................203
Table 14.2-2.2.1 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase – Subset of Full Analysis Set entering the TFR phase ..............................204


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Table 14.2-2.2.2 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase – Subset of Per Protocol Analysis Set entering the TFR phase.................205
Table 14.2-2.2.3 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase, SDV sensitivity – Subset of Full Analysis Set entering the TFR phase...205
Table 14.2-2.2.4 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase, SDV sensitivity – Subset of Per Protocol Analysis Set entering the 
TFR phase............................................................................................................205
Table 14.2-2.3 Kaplan-Meier analysis of overall survival from Randomization–
Randomized Set...................................................................................................206
Table 14.2-2.4 Kaplan-Meier analysis of progression-free survival during the TFR 
phase –- Subset of Full Analysis Set entering the TFR phase.............................207
Table 14.2-2.5 Kaplan-Meier analysis of overall survival from Randomization, SDV 
sensitivity –Randomized Set ...............................................................................208
Table 14.2-2.6 Kaplan-Meier analysis of progression-free survival during the TFR 
phase, SDV sensitivity –- Subset of Full Analysis Set entering the TFR phase .208
Table 14.2-3.1 Major molecular response during pre-randomization 
Induction/Consolidation phase –Full Analysis Set..............................................209
Table 14.2-3.1.1 Major molecular response during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................210
Table 14.2-3.2 Major molecular response during post-randomization consolidation 
phase (ARM 2)– Subset of Full Analysis Set randomized to Arm 2...................211
Table 14.2-3.2.1 Major molecular response during post-randomization consolidation 
phase (ARM 2) – LSC sub-study Full Analysis Set randomized to Arm 2.........211
Table 14.2-3.3 Major molecular response during TFR phase –Subset of Full Analysis 
Set patients entered TFR phase ...........................................................................212
Table 14.2-3.4 Major molecular response during re-treatment phase–Subset of Full 
Analysis Set patients entered re- treatment phase ...............................................213
Table 14.2-3.5 Major molecular response during TFR phase –Subset of Full Analysis 
Set patients entered TFR phase with MR4.0 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................214
Table 14.2-3.6 Major molecular response during TFR phase –Subset of Full Analysis 
Set patients entered TFR phase with MR4.5 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................214
Table 14.2-3.7 Major molecular response during TFR phase, SDV sensitivity –
Subset of Full Analysis Set patients entered TFR phase.....................................214
Table 14.2-3.8 Major molecular response during re-treatment phase, SDV sensitivity 
–Subset of Full Analysis Set patients entered re- treatment phase......................214
Table 14.2-4.1 Molecular response 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................215
Table 14.2-4.1.1 Molecular response 4.0 during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................215
Table 14.2-4.2.1 Molecular response 4.0 during post-randomization consolidation 
phase (ARM 2) – Subset of Full Analysis Set randomized to Arm 2..................215


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Table 14.2-4.2.2 Molecular response 4.0 during post-randomization consolidation 
phase (ARM 2) – Subset of  Per Protocol randomized to Arm 2 ........................215
Table 14.2-4.2.11 Molecular response 4.0 during post-randomization consolidation 
phase (ARM 2) – Subset of  LSC sub-study Full Analysis Set randomized to 
Arm 2...................................................................................................................215
Table 14.2-4.3.1 Molecular response 4.0 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase..................................................................................216
Table 14.2-4.3.2 Molecular response 4.0 during TFR phase – Subset of Per Protocol 
Analysis Set entering the TFR phase...................................................................216
Table 14.2-4.3.3 Molecular response 4.0 during TFR phase , SDV sensitivity –
Subset of Full Analysis Set entering the TFR phase ...........................................216
Table 14.2-4.4 Molecular response 4.0 during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................217
Table 14.2-4.5 Molecular response 4.0 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.0 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................217
Table 14.2-4.6 Molecular response 4.0 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.5 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................217
Table 14.2-4.7 Molecular response 4.0 during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase...............................217
Table 14.2-5.1 Molecular response 4.5 during pre-randomization 
Induction/Consolidation– Full Analysis Set........................................................218
Table 14.2-5.1.1 Molecular response 4.5 during pre-randomization 
Induction/Consolidation– LSC sub-study Full Analysis Set...............................218
Table 14.2-5.2 Molecular response 4.5 during post-randomization consolidation 
phase (ARM 2) – Subset of Full Analysis Set randomized to Arm 2..................218
Table 14.2-5.2.1 Molecular response 4.5 during post-randomization consolidation 
phase (ARM 2) – Subset of LSC sub-study Full Analysis Set randomized to  
Arm 2...................................................................................................................218
Table 14.2-5.3 Molecular response 4.5 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase..................................................................................218
Table 14.2-5.4 Molecular response 4.5 during re-treatment phase – Subset of Full
Analysis Set entering the re-treatment phase.......................................................218
Table 14.2-5.5 Molecular response 4.5 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.0 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................219
Table 14.2-5.6 Molecular response 4.5 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.5 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................219
Table 14.2-5.7 Molecular response 4.5 during TFR phase, SDV sensitivity – Subset 
of Full Analysis Set entering the TFR phase.......................................................219
Table 14.2-5.8 Molecular response 4.5 during re-treatment phase, SDV sensitivity  –
Subset of Full Analysis Set entering the re-treatment phase...............................219


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Table 14.2-6.1 Raw cumulative incidence MMR during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................220
Table 14.2-6.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................221
Table 14.2-6.2 Raw cumulative incidence MMR during post-randomization 
Consolidation phase (ARM 2)  - Subset of  Full Analysis Set patients 
randomized to ARM 2 .........................................................................................221
Table 14.2-6.2.1 Raw cumulative incidence MMR during post-randomization 
Consolidation phase (ARM 2)  - Subset of  LSC sub-study Fulls Anslysis Set 
randomized to ARM 2 .........................................................................................221
Table 14.2-6.3 Raw cumulative incidence of MMR during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................222
Table 14.2-6.4 Raw cumulative incidence of MMR during re-treatment phase , SDV 
sensitivity  – Subset of Full Analysis Set entering the re-treatment phase..........222
Table 14.2-7.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................222
Table 14.2-7.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................222
Table 14.2-7.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
ARM 2 .................................................................................................................223
Table 14.2-7.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) – Subset of LSC sub-study Full Analysis Set  
randomized to ARM 2 .........................................................................................223
Table 14.2-7.3 Raw cumulative incidence of MR 4.0 during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................223
Table 14.2-7.4 Raw cumulative incidence of MR 4.0 during re-treatment phase, SDV 
sensitivity  – Subset of Full Analysis Set entering the re-treatment phase..........223
Table 14.2-8.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................224
Table 14.2-8.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................224
Table 14.2-8.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................224
Table 14.2-8.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) - Subset of LSC sub-study Full Analysis Set 
randomized to Arm 2...........................................................................................224
Table 14.2-8.3 Raw cumulative incidence of MR 4.5 during re-treatment phase -
Subset of Full Analysis Set entering the re-treatment phase...............................224
Table 14.2-8.4 Raw cumulative incidence of MR 4.5 during re-treatment phase , 
SDV sensitivity - Subset of Full Analysis Set entering the re-treatment phase ..225
Table 14.2-9.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – Full 
Analysis Set .........................................................................................................226


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Table 14.2-9.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – LSC 
sub-study Full Analysis Set .................................................................................226
Table 14.2-9.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to Arm 2 ..............................................227
Table 14.2-9.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of LSC sub-study Full Analysis Set randomized to Arm 2 .....................228
Table 14.2-9.3 Raw cumulative incidence of MMR during re-treatment phase by 
halving time of BCR-ABL (IS) ratio – Subset of Full Analysis Set entering 
the re-treatment phase..........................................................................................228
Table 14.2-10.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – Full 
Analysis Set .........................................................................................................229
Table 14.2-.10.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – LSC 
sub-study Full Analysis Set .................................................................................229
Table 14.2-10.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to Arm 2 ..............................................229
Table 14.2-10.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of LSC sub-study Full Analysis Set randomized to Arm 2 .....................229
Table 14.2-10.3 Raw cumulative incidence of MR4.0 during re-treatment phase by 
halving time of BCR-ABL (IS) ratio – Subset of Full Analysis Set entering 
the re-treatment phase..........................................................................................229
Table 14.2-11.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – Full 
Analysis Set .........................................................................................................230
Table 14.2-.11.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – LSC 
sub-study Full Analysis Set .................................................................................230
Table 14.2-11.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to Arm 2 ..............................................230
Table14.2-11.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of LSC sub-study Full Analysis Set randomized to Arm 2 .....................230
Table 14.2-11.3 Raw cumulative incidence of MR4.5 during re-treatment phase by 
halving time of BCR-ABL (IS) ratio – Subset of Full Analysis Set entering 
the re-treatment phase..........................................................................................230
Table 14.2-12.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – Full 
Analysis Set .........................................................................................................231


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Table 14.2-12.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – LSC 
sub-study Full Analysis Set .................................................................................231
Table 14.2-12.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................231
Table 14.2-12.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
LSC sub-study Full Analysis Set randomized to Arm 2......................................232
Table 14.2-12.3 Raw cumulative incidence of MMR during re-treatment phase by 
BCR-ABL (IS) ratio at Month 3 – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................232
Table 14.2-13.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – Full 
Analysis Set .........................................................................................................233
Table 14.2-13.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – LSC 
sub-study Full Analysis Set .................................................................................233
Table 14.2-13.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................233
Table 14.2-13.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
LSC sub-study Full Analysis Set randomized to Arm 2......................................233
Table 14.2-13.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by 
BCR-ABL (IS) ratio at Month 3 – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................233
Table 14.2-14.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – Full 
Analysis Set .........................................................................................................234
Table 14.2-14.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – LSC 
sub-study Full Analysis Set .................................................................................234
Table 14.2-14.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................234
Table 14.2-14.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
LSC sub-study Full Analysis Set randomized to Arm 2......................................234
Table 14.2-14.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by 
BCR-ABL (IS) ratio at Month 3 – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................234
Table 14.2-15.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by Sokal Risk category– Full Analysis Set........235
Table 14.2-15.2 Raw cumulative incidence of MR4.0 during pre-randomization 
Induction/Consolidation phase by Sokal Risk category– Full Analysis Set........235


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Table 14.2-15.3 Raw cumulative incidence of MR4.5 during pre-randomization 
Induction/Consolidation phase by Sokal Risk category– Full Analysis Set........236
Table 14.2-16.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by time since initial diagnosis of CML– Full 
Analysis Set .........................................................................................................237
Table 14.2-16.2 Raw cumulative incidence of MR4.0 during pre-randomization 
Induction/Consolidation phase by time since initial diagnosis of CML – Full 
Analysis Set .........................................................................................................238
Table 14.2-16.3 Raw cumulative incidence of MR4.5 during pre-randomization 
Induction/Consolidation phase by time since initial diagnosis of CML – Full 
Analysis Set .........................................................................................................238
Table 14.2-17.1 Suboptimal response up to 24 months of pre-randomization 
Induction/Consolidation phase -  Full Analysis Set patients who prematurely 
discontinued the pre-randomization Induction/Consolidation phase ..................239
Table 14.2-17.2 Suboptimal response up to 12 months of post-randomization 
Consolidation phase (ARM 2)  - Subset of  Full Analysis Set patients who 
prematurely discontinued the Induction/Consolidation phase randomized to 
Arm 2...................................................................................................................240
Table 14.2-18.1 Suboptimal response up to 24 months of pre-randomization 
Induction/Consolidation phase - Full Analysis Set .............................................240
Table 14.2-18.2 Suboptimal response up to 12 months of post-randomization 
Consolidation phase - Subset of Full Analysis Set, randomized to ARM 2........240
Table 14.2-19.1 Kinetics of BCR-ABL (IS) ratio during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................241
Table 14.2-19.1.1 Kinetics of BCR-ABL (IS) ratio during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................241
Table 14.2-19.2 Kinetics of BCR-ABL (IS) ratio during post-randomization 
consolidation phase (ARM 2) –Subset of Full Analysis Set randomized to
Arm 2...................................................................................................................242
Table 14.2-19.2.1 Kinetics of BCR-ABL (IS) ratio during post-randomization 
consolidation phase (ARM 2) –Subset of LSC sub-study Full Analysis Set 
randomized to Arm 2...........................................................................................242
Table 14.2-19.3 Kinetics of BCR-ABL (IS) ratio during TFR phase – Subset of Full 
Analysis Set entering the TFR phase...................................................................243
Table 14.2-19.4 Kinetics of BCR-ABL (IS) ratio during re-treatment phase – Subset 
of Full Analysis Set entering the re-treatment phase...........................................245
Table 14.2-19.5 Kinetics of BCR-ABL (IS) ratio during TFR phase, SDV sensitivity   
– Subset of Full Analysis Set entering the TFR phase ........................................246
Table 14.2-19.6 Kinetics of BCR-ABL (IS) ratio during re-treatment phase , SDV 
sensitivity  – Subset of Full Analysis Set entering the re-treatment phase..........246
Table 14.2-20.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline..................................................................................................247


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Table 14.2-20.2 Raw cumulative incidence of MMR during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MMR at baseline, randomized to ARM 2.............................................247
Table 14.2-21.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching MR 
4.0 at baseline ......................................................................................................247
Table 14.2-21.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MR 4.0 at baseline, randomized to ARM 2 ..........................................247
Table 14.2-22.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase -   Full Analysis Set patients not reaching MR 
4.5 at baseline ......................................................................................................247
Table 14.2-22.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2)  - Subset of  Full Analysis Set patients not 
reaching MR 4.5 at baseline, randomized to ARM 2 ..........................................248
Table 14.2-22.3 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline..................................................................................................248
Table 14.2-22.4 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MMR at baseline, randomized to ARM 2.............................................248
Table 14.2-22.5 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline..................................................................................................248
Table 14.2-22.6 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MMR at baseline, randomized to ARM 2.............................................248
Table 14.2-23.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline -  Full 
Analysis Set .........................................................................................................249
Table 14.2-23.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at baseline– LSC sub-
study Full Analysis Set........................................................................................250
Table 14.2-23.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
Full Analysis Set, randomized to ARM 2............................................................250
Table 14.2-23.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................251
Table 14.2-23.3 Raw cumulative incidence of MMR during re-treatment phase by 
BCR-BL(IS) ratio at baseline – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................251
Table 14.2-24.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set .........................................................................................................252


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Table 14.2-24.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at baseline– LSC sub-
study Full Analysis Set........................................................................................252
Table 14.2-24.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
Full Analysis Set, randomized to ARM 2............................................................252
Table 14.2-24.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................252
Table 14.2-24.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by 
BCR-BL(IS) ratio at baseline – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................252
Table 14.2-25.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set .........................................................................................................253
Table 14.2-25.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at baseline– LSC sub-
study Full Analysis Set........................................................................................253
Table 14.2-25.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
Full Analysis Set, randomized to ARM 2............................................................253
Table 14.2-25.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................253
Table 14.2-25.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by 
BCR-BL(IS) ratio at baseline – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................253
Table 14.2-26.1 Raw cumulative loss of MMR during TFR phase –Subset of Full 
Analysis Set entering the TFR phase...................................................................254
Table 14.2-26.2 Raw cumulative loss of MR4.0 during TFR phase –Subset of Full 
Analysis Set entering the TFR phase...................................................................255
Table 14.2-26.3 Raw cumulative loss of MR4.5 during TFR phase –Subset of Full 
Analysis Set entering the TFR phase with MR4.5 ..............................................255
Table 14.2-26.4 Raw cumulative loss of MMR during TFR phase, SDV sensitivity  –
Subset of Full Analysis Set entering the TFR phase ...........................................256
Table 14.2-26.5 Raw cumulative loss of MR4.0 during TFR phase, SDV sensitivity 
–Subset of Full Analysis Set entering the TFR phase .........................................256
Table 14.2-26.6 Raw cumulative loss of MR4.5 during TFR phase, SDV sensitivity 
–Subset of Full Analysis Set entering the TFR phase with MR4.5.....................256
Table 14.2-27.1 Descriptive Statistics for CD34 cells: Total percentage – LSC sub-
study Full Analysis Set........................................................................................257
Table 14.2-28.1 Descriptive Statistics for CD34+/CD38+ cells: Percentage from 
total CD34+ cells – LSC sub-study Full Analysis Set.........................................259
Table 14.2-28.2 Descriptive Statistics for number of events sorted in CD34+/CD38+ 
cells – LSC sub-study Full Analysis Set..............................................................260


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Table 14.2-28.3 Ph+ by HIS status, in CD34+/CD38+ cells – LSC sub-study Full 
Analysis Set .........................................................................................................261
Table 14.2-28.4 Descriptive statistics of Ph+ in CD34+/CD38+ cells– LSC sub-study 
Full Analysis Set..................................................................................................261
Table 14.2-28.5 BCR-ABL by RT-PCR status, in CD34+/CD38+ cells – LSC sub-
study Full Analysis Set........................................................................................261
Table 14.2-29.1 Descriptive Statistics for CD34+/CD38- cells: Percentage from total 
CD34+ cells – LSC sub-study Full Analysis Set.................................................262
Table 14.2-29.2 Descriptive Statistics for number of events sorted in CD34+/CD38-
cells – LSC sub-study Full Analysis Set..............................................................262
Table 14.2-29.3 Ph+ by HIS status, in CD34+/CD38- cells – LSC sub-study Full 
Analysis Set .........................................................................................................262
Table 14.2-29.4 Descriptive statistics of Ph+ in CD34+/CD38- cells– LSC sub-study 
Full Analysis Set..................................................................................................262
Table 14.2-29.5 BCR-ABL by RT-PCR status, in CD34+/CD38- cells – LSC sub-
study Full Analysis Set........................................................................................262
Table 14.2-30.1 Descriptive Statistics for Immunophenotypically aberrant CD34+ 
cells: Percentage from total CD34+ cells –LSC sub-study Full Analysis Set.....263
Table 14.2-30.2 Descriptive Statistics for number of events sorted in 
Immunophenotypically aberrant CD34+ cells – LSC sub-study Full Analysis 
Set ........................................................................................................................263
Table 14.2-30.3 Ph+ by HIS status, in Immunophenotypically aberrant CD34+ cells 
– LSC sub-study Full Analysis Set......................................................................263
Table 14.2-30.4 Descriptive statistics of Ph+ in Immunophenotypically aberrant
CD34+ cells– LSC sub-study Full Analysis Set..................................................263
Table 14.2-30.5 BCR-ABL by RT-PCR status, in Immunophenotypically aberrant
CD34+ cells – LSC sub-study Full Analysis Set.................................................263
Table 14.2-31.1 Descriptive Statistics for Immunophenotypically aberrant CD34-
cells: Percentage from total CD34+ cells – LSC sub-study Full Analysis Set ..264
Table 14.2-31.2 Descriptive Statistics for number of events sorted in 
Immunophenotypically aberrant CD34- cells- LSC sub-study Full Analysis 
Set ........................................................................................................................264
Table 14.2-31.3 Ph+ by HIS status, in Immunophenotypically aberrant CD34- cells –
LSC sub-study Full Analysis Set.........................................................................264
Table 14.2-31.4 Descriptive statistics of Ph+ in Immunophenotypically aberrant 
CD34- cells– LSC sub-study Full Analysis Set...................................................264
Table 14.2-31.5 BCR-ABL by RT-PCR status, in Immunophenotypically aberrant 
CD34- cells – LSC sub-study Full Analysis Set..................................................264
Table 14.2-32.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by duration of prior exposure to Imatinib -  
Full Analysis Set..................................................................................................265
Table 14.2-32.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by by prior Imatib treatment duration – LSC 
sub-study Full Analysis Set .................................................................................266


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Table 14.2-32.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
Full Analysis Set, randomized to ARM 2............................................................266
Table 14.2-32.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................267
Table 14.2-32.3 Raw cumulative incidence of MMR during re-treatment phase by 
prior Imatib treatment duration – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................267
Table 14.2-33.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration - Full 
Analysis Set .........................................................................................................268
Table 14.2-33.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration – LSC sub-
study Full Analysis Set........................................................................................268
Table 14.2-33.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
Full Analysis Set, randomized to ARM 2............................................................268
Table 14.2-33.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................268
Table 14.2-33.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by 
prior Imatib treatment duration – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................268
Table 14.2-34.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration - Full 
Analysis Set .........................................................................................................269
Table 14.2-34.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration – LSC sub-
study Full Analysis Set........................................................................................269
Table 14.2-34.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
Full Analysis Set, randomized to ARM 2............................................................269
Table 14.2-34.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................269
Table 14.2-34.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by 
prior Imatib treatment duration – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................269
Section 14.3 – Safety data ...............................................................................................271
Table 14.3-1.1 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation– Safety Set...................................................................271
Table 14.3-1.1.1 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation– LSC sub-study Safety Set ..........................................272


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Table 14.3-1.2 Duration of exposure to study treatment during post-randomization 
Consolidation phase (ARM 2) - Subset of Safety Set randomized to Arm 2......272
Table 14.3-1.2.1 Duration of exposure to study treatment during post-randomization 
Consolidation phase (ARM 2) - Subset of LSC sub-study Safety Set 
randomized to Arm 2...........................................................................................272
Table 14.3-1.1.3 Duration of exposure to study treatment during re-treatment phase –
Subset of Safety Set entering the re-treatment phase ..........................................273
Table 14.3-1.1.21 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation phase, by stable MR4.0 at 24 months and halving 
time - Safety Set...................................................................................................273
Table 14.3-1.1.22 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation phase, by stable MR4.0 by 24 months and halving 
time - Safety Set...................................................................................................275
Table 14.3-2.1 Relative dose intensity and average daily dose during pre-
randomization Induction/Consolidation phase – Safety Set................................276
Table 14.3-2.1.1 Relative dose intensity and average daily dose during pre-
randomization Induction/Consolidation phase – LSC sub-study Safety Set.......277
Table 14.3-2.2 Relative dose intensity and average daily dose during post-
randomization consolidation phase (ARM 2) – Subset of Safety Set 
randomized to Arm 2...........................................................................................277
Table 14.3-2.2.1 Relative dose intensity and average daily dose during post-
randomization consolidation phase (ARM 2) – Subset of LSC sub-study 
Safety Set randomized to Arm 2..........................................................................277
Table 14.3-2.3 Relative dose intensity and average daily dose during re-treatment 
phase – Subset of Safety Set entering the re-treatment phase .............................278
Table 14.3-3.1 Dose reduction and interruption during pre-randomization 
Induction/Consolidation phase - Safety Set.........................................................279
Table 14.3-3.1.1 Dose reduction and interruption during pre-randomization 
Induction/Consolidation phase – LSC sub-study Safety Set...............................279
Table 14.3-3.2 Dose reduction and interruption during post-randomization 
consolidation phase (ARM 2) – Subset of Safety Set randomized to Arm 2 ......280
Table 14.3-3.2.1 Dose reduction and interruption during post-randomization 
consolidation phase (ARM 2) – Subset of LSC sub-study Safety Set 
randomized to Arm 2...........................................................................................280
Table 14.3-3.3 Dose reduction and interruption during re-treatment phase – Subset of 
Safety Set entering the re-treatment phase ..........................................................281
Table 14.3-4.1 Concomitant medication by ATC class and preferred term during pre-
randomization Induction/Consolidation phase Full Analysis Set........................282
Table 14.3-4.1.1 Concomitant medication by ATC class and preferred term during
pre-randomization Induction/Consolidation phase LSC sub-study Full 
Analysis Set .........................................................................................................282
Table 14.3-4.2 Concomitant medication by ATC class and preferred term during 
post-randomization consolidation phase (ARM 2)– Subset of Full Analysis 
Set randomized to Arm 2.....................................................................................283


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Table 14.3-4.2.1 Concomitant medication by ATC class and preferred term during 
post-randomization consolidation phase (ARM 2)– Subset of LSC sub-study 
Full Analysis Set randomized to Arm 2 ..............................................................284
Table 14.3-4.3 Concomitant medication by ATC class and preferred term during 
TFR phase – Subset of Full Analysis Set entering the TFR phase......................285
Table 14.3-4.4 Concomitant medication by ATC class and preferred term during re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase..286
Table 14.3-5.1.1 Hematology shift table based on CTCAE grade during Pre-
Randomization pre-randomization Induction/Consolidation –Full Analysis 
Set ........................................................................................................................287
Table 14.3-5.1.2 Hematology shift table based on CTCAE grade during post-
randomization consolidation phase (ARM 2)– Subset of Full Analysis Set 
randomized to Arm 2...........................................................................................289
Table 14.3-5.1.3 Hematology shift table based on CTCAE grade during re-treatment 
phase – Subset of Full Analysis Set entering the re-treatment phase..................290
Table 14.3-5.1.4 Hematology shift table based on CTCAE grade during whole study 
period – Full Analysis Set ...................................................................................292
Table 14.3-5.1.5 Hematology shift table based on CTCAE grade during re-treatment 
phase, SDV sensitivity   – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................293
Table 14.3-5.1.6 Hematology shift table based on CTCAE grade during whole study 
period , SDV sensitivity– Full Analysis Set........................................................293
Table 14.3-5.2.1 Biochemistry shift table based on CTCAE grade during post-
randomization consolidation phase (ARM 2)– Subset of Full Analysis Set 
randomized to Arm 2...........................................................................................294
Table 14.3-5.2.2 Biochemistry shift table based on CTCAE grade during re-
treatment phase– Subset of Full Analysis Set entering the re-treatment phase...294
Table 14.3-5.2.3 Biochemistry shift table based on CTCAE grade during whole 
study period – Full Analysis Set..........................................................................294
Table 14.3-5.2.4 Biochemistry shift table based on CTCAE grade during re-
treatment phase, SDV sensitivity– Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................294
Table 14.3-5.2.5 Biochemistry shift table based on CTCAE grade during whole 
study period, SDV sensitivity – Full Analysis Set ..............................................294
Table 14.3-6.1.1 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during post-randomization consolidation phase 
(ARM 2)– Subset of Full Analysis Set randomized to Arm 2.............................295
Table 14.3-6.1.2 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................296
Table 14.3-6.1.3 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period –Full Analysis Set.........297
Table 14.3-6.1.4 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase...............................298


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Table 14.3-6.1.5 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period, SDV sensitivity –Full 
Analysis Set .........................................................................................................298
Table 14.3-6.2.1 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during post-randomization consolidation phase 
(ARM 2) – Subset of Full Analysis Set randomized to Arm 2............................299
Table 14.3-6.2.2 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................299
Table 14.3-6.2.3 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period –Full Analysis Set.........299
Table 14.3-6.2.4 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase...............................299
Table 14.3-6.2.5 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period, SDV sensitivity –Full 
Analysis Set .........................................................................................................299
Table 14.3-7.1 ECG shift table based on notable values during Pre-randomization 
Induction Consolidation–Full Analysis Set.........................................................300
Table 14.3-7.2 ECG shift table based on notable values during post-randomization 
consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................301
Table 14.3-7.3 ECG shift table based on notable values during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................302
Table 14.3-7.4 Notable ECG values during pre-randomization Ind/Cons –Full 
Analysis Set .........................................................................................................303
Table 14.3-7.5 Notable ECG values during post-randomization consolidation phase 
(ARM 2)– Subset of Full Analysis Set randomized to Arm 2.............................304
Table 14.3-7.6 Notable ECG values during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................305
Table 14.3-7.7 ECG shift table based on notable values during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase..305
Table 14.3-7.8 Notable ECG values during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase...............................305
Table 14.3-8.1 Echocardiography assessment at baseline – Full Analysis Set...............306
Table 14.3-8.2 Echocardiography shift table based on overall interpretation - Full 
Analysis Set .........................................................................................................307
Table 14.3-8.3 Echocardiography shift table based on overall interpretation, SDV 
sensitivity - Full Analysis Set..............................................................................308
Table 14.3-9.1 Summary statistics of total cholesterol, HDL, LDL, glucose, 
microalbumin and HbA1c over Induction/Consolidation phase – Full 
Analysis Set .........................................................................................................309
Table 14.3-9.2.1 Total cholesterol shift table based on specific levels during 
Induction Consolidation  – Full Analysis Set......................................................310


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Table 14.3-9.2.2 Total cholesterol shift table based on specific levels during TFR 
phase  – Subset of Full Analysis Set entering the TFR phase .............................311
Table 14.3-9.2.3 Total cholesterol shift table based on specific levels during Re-
treatment phase  – Subset of Full Analysis Set entering the Re-treatment 
phase ....................................................................................................................311
Table 14.3-9.2.4 Total cholesterol shift table based on specific levels during TFR 
phase, SDV sensitivity  – Subset of Full Analysis Set entering the TFR phase..311
Table 14.3-9.2.5 Total cholesterol shift table based on specific levels during Re-
treatment phase, SDV sensitivity  – Subset of Full Analysis Set entering the 
Re-treatment phase ..............................................................................................312
Table 14.3-10.1.1 Fasting glucose shift table based on specific levels during 
Induction Consolidation – Full Analysis Set.......................................................313
Table 14.3-10.1.2 Fasting glucose shift table based on specific levels during TFR 
phase  – Subset of Full Analysis Set entering the TFR phase .............................314
Table 14.3-10.1.3 Fasting glucose shift table based on specific levels during Re-
treatment phase  – Subset of Full Analysis Set entering the Re-treatment 
phase ....................................................................................................................314
Table 14.3-10.1.4 Fasting glucose shift table based on specific levels during TFR 
phase, SDV sensitivity   – Subset of Full Analysis Set entering the TFR phase.314
Table 14.3-10.1.5 Fasting glucose shift table based on specific levels during Re-
treatment phase, SDV sensitivity   – Subset of Full Analysis Set entering the 
Re-treatment phase ..............................................................................................315
Table 14.3-11.1 Vital Signs during Induction Consolidation – Full Analysis Set..........316
Table 14.3-11.2 Vital Signs during TFR phase – Subset of Full Analysis Set entering 
the TFR phase......................................................................................................319
Table 14.3-11.3 Vital Signs during Re-treatment phase  – Subset of Full Analysis Set 
entering the Re-treatment phase ..........................................................................319
Table 14.3-11.4 Vital Signs during TFR phase, SDV sensitivity – Subset of Full 
Analysis Set entering the TFR phase...................................................................320
Table 14.3-11.5 Vital Signs during Re-treatment phase, SDV sensitivity – Subset of 
Full Analysis Set entering the Re-treatment phase..............................................320
Table 14.3-12.1 Survival follow-up – Full Analysis Set.................................................321
Table 14.3-12.2 Survival follow-up, SDV sensitivity  – Full Analysis Set ....................322
Table 14.3-13.1 Safety follow-up – Full analysis Set .....................................................323
Table 14.3-13.2 Safety follow-up, SDV sensitivity  – Full analysis Set.........................323
Section 14.3.1 – Displays of adverse events ...................................................................324
Figure 14.3.1-1.1 Kaplan-Meier analysis of time-to-first CVEs during the pre-
randomization Induction/Consolidation phase – Full Analysis Set.....................324
Figure 14.3.1-1.2 Kaplan-Meier analysis of time-to-first CVEs during the post-
randomization consolidation phase (ARM 2) – Subset of Full Analysis Set 
randomized to Arm 2...........................................................................................325
Figure 14.3.1-1.3 Kaplan-Meier analysis of time-to-first CVEs during the the TFR 
phase – Subset of Full Analysis Set entering the TFR phase ..............................326


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Figure 14.3.1-1.4 Kaplan-Meier analysis of time-to-first CVEs during the re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase..326
Figure 14.3.1-2.1 Number of sorted events by HIS CD34+/CD38+ cells ......................327
Figure 14.3.1-2.2 Number of sorted events by PCR CD34+/CD38+ cells .....................328
Figure 14.3.1-3.1 Number of sorted events by HIS CD34+/CD38- cells .......................328
Figure 14.3.1-3.2 Number of sorted events by PCR CD34+/CD38- cells ......................328
Figure 14.3.1-4.1 Number of sorted events by HIS Immunophenotypically aberrant 
CD34+ cells .........................................................................................................328
Figure 14.3.1-4.2 Number of sorted events by PCR Immunophenotypically aberrant 
CD34+ cells .........................................................................................................328
Figure 14.3.1-5.1 Number of sorted events by HIS Immunophenotypically aberrant 
CD34- cells..........................................................................................................328
Figure 14.3.1-5.2 Number of sorted events by PCR Immunophenotypically aberrant 
CD34- cells..........................................................................................................328
Figure 14.3.1-6.1 Number of HIS+ subjects CD34+/CD38+ cells – LSC substudy 
Full Analysis Set..................................................................................................329
Figure 14.3.1-6.2 Number of PCR subjects CD34+/CD38+ cells – LSC substudy 
Full Analysis Set..................................................................................................330
Figure 14.3.1-7.1 Number of HIS+ subjects CD34+/CD38- cells – LSC substudy 
Full Analysis Set..................................................................................................330
Figure 14.3.1-7.2 Number of PCR subjects CD34+/CD38- cells – LSC substudy Full 
Analysis Set .........................................................................................................330
Figure 14.3.1-8.1 Number of HIS+ subjects Immunophenotypically aberrant CD34+ 
cells – LSC substudy Full Analysis Set...............................................................330
Figure 14.3.1-8.2 Number of PCR subjects Immunophenotypically aberrant CD34+ 
cells – LSC substudy Full Analysis Set...............................................................330
Figure 14.3.1-9.1 Number of HIS+ subjects Immunophenotypically aberrant CD34-
cells – LSC substudy Full Analysis Set...............................................................330
Figure 14.3.1-9.2 Number of PCR subjects Immunophenotypically aberrant CD34-
cells – LSC substudy FAS...................................................................................330
Figure 14.3.1-10 Number of patients with detectable LSC – LSC substudy Full 
Analysis Set .........................................................................................................331
Table 14.3.1-1.1 Overall summary of treatment-emergent adverse events occurring 
during pre-randomization Induction/consolidation phase – Full Analysis Set....332
Table 14.3.1-1.2 Overall summary of treatment-emergent adverse events occurring 
during post-randomization consolidation phase (ARM 2) – Subset of Full 
Analysis Set randomized to Arm 2......................................................................334
Table 14.3.1-1.3 Overall summary of treatment-emergent adverse events occurring 
during re-treatment phase – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................336
Table 14.3.1-1.4 Overall summary of adverse events occurring during TFR phase –
Subset of Full Analysis Set entering the TFR phase ...........................................337


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Table 14.3.1-2.1 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during pre-randomization Induction/consolidation phase – Full 
Analysis Set .........................................................................................................338
Table 14.3.1-2.2 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during post-randomization consolidation phase (ARM 2) – Subset 
of Full Analysis Set randomized to Arm 2..........................................................338
Table 14.3.1-2.3 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during re-treatment phase – Subset of Full Analysis Set entering 
the re-treatment phase..........................................................................................338
Table 14.3.1-2.4 Overall summary of frequent [1] adverse events occurring during 
TFR phase – Subset of Full Analysis Set entering the TFR phase......................339
Table 14.3.1-3.1.1 Treatment Emergent adverse events incidence, regardless of study 
drug relationship, occurring during pre-randomization 
Induction/consolidation phase by system organ class and preferred term -
overall and maximum grade 3/4 – Full Analysis Set...........................................340
Table 14.3.1-3.1.2 Treatment Emergent adverse events occurence, regardless of 
study drug relationship, occurring during pre-randomization 
Induction/consolidation phase by system organ class and preferred term -
overall and maximum grade 3/4 – Full Analysis Set...........................................341
Table 14.3.1-3.2.1 Treatment Emergent adverse events incidence, regardless of study 
drug relationship, occurring during post-randomization consolidation phase 
(ARM 2) by system organ class and preferred term - overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................342
Table 14.3.1-3.2.2 Treatment Emergent adverse events occurence, regardless of 
study drug relationship, occurring during post-randomization consolidation 
phase (ARM 2) by system organ class and preferred term - overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ..........343
Table 14.3.1-3.3.1 Treatment-emergent adverse events incidence, regardless of study 
drug relationship, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................344
Table 14.3.1-3.3.2 Treatment-emergent adverse events occurrence, regardless of 
study drug relationship, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................345
Table 14.3.1-3.4.1 Adverse events incidence, regardless of study drug relationship, 
by system organ class and preferred term during TFR phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase.......345
Table 14.3.1-3.4.2 Adverse events occurrence, regardless of study drug relationship, 
by system organ class and preferred term during TFR phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase.......345
Table 14.3.1-3.5.1 Frequent [1] Treatment Emergent adverse events incidence, 
regardless of study drug relationship occurring during pre-randomization 
Induction/consolidation phase by system organ class and preferred term -
overall and maximum grade 3/4 – Full Analysis Set...........................................346


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Table 14.3.1-3.5.2 Frequent [1] Treatment Emergent adverse events incidence, 
regardless of study drug relationship occurring during post-randomization 
consolidation phase (ARM 2) by system organ class and preferred term-
overall and maximum grade 3/4  – Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................346
Table 14.3.1-3.5.3 Frequent [1] Treatment Emergent adverse events incidence, 
regardless of study drug relationship occurring during re-treatment phase by 
system organ class and preferred term- overall and maximum grade 3/4  –
Subset of Full Analysis Set entering the re-treatment phase...............................347
Table 14.3.1-3.5.4 Frequent [1] adverse events incidence, regardless of study drug 
relationship occurring during TFR phase by system organ class and preferred 
term - overall and maximum grade 3/4 – Subset of Full Analysis Set entering 
the TFR phase......................................................................................................347
Table 14.3.1-4.1.1 Serious treatment-emergent adverse events incidence, regardless 
of study drug relationship, by system organ class and preferred term during 
pre-randomization Induction/consolidation phase – overall and maximum 
grade 3/4 –Full Analysis Set................................................................................348
Table 14.3.1-4.1.2 Serious treatment-emergent adverse events occurence, regardless 
of study drug relationship, by system organ class and preferred term during 
pre-randomization Induction/consolidation phase – overall and maximum 
grade 3/4 –Full Analysis Set................................................................................348
Table 14.3.1-4.2.1 Serious treatment-emergent adverse events incidence, regardless 
of study drug relationship, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................349
Table 14.3.1-4.2.2 Serious treatment-emergent adverse events occurrence, regardless 
of study drug relationship, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................349
Table 14.3.1-4.3.1 Serious treatment-emergent adverse events incidence, regardless 
of study drug relationship, by system organ class and preferred term during 
re-treatment phase – overall and maximum grade 3/4 – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................350
Table 14.3.1-4.3.2 Serious treatment-emergent adverse events occurrence, regardless 
of study drug relationship, by system organ class and preferred term during 
re-treatment phase – overall and maximum grade 3/4 – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................350
Table 14.3.1-4.4.1 Serious adverse events incidence, regardless of study drug 
relationship, by system organ class and preferred term during TFR phase –
overall and maximum grade 3/4 – Subset of Full Analysis Set entering the 
TFR phase............................................................................................................350
Table 14.3.1-4.4.2 Serious adverse events occurence, regardless of study drug 
relationship, by system organ class and preferred term during TFR phase –
overall and maximum grade 3/4 – Subset of Full Analysis Set entering the 
TFR phase............................................................................................................350
Table 14.3.1-4.5.1 Frequent [1] Serious Treatment Emergent adverse events 
incidence, regardless of study drug relationship occurring during pre-


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randomization Induction/consolidation phase by system organ class and 
preferred term - overall and maximum grade 3/4 – Full Analysis Set ................351
Table 14.3.1-4.5.2 Frequent [1] Serious Treatment Emergent adverse events 
incidence, regardless of study drug relationship occurring during post-
randomization consolidation phase (ARM 2) by system organ class and 
preferred term - overall and maximum grade 3/4  – Subset of Full Analysis 
Set randomized to Arm 2.....................................................................................351
Table 14.3.1-4.5.3 Frequent [1] Serious Treatment Emergent adverse events 
incidence, regardless of study drug relationship occurring during re-treatment 
phase by system organ class and preferred term - overall and maximum grade 
3/4  – Subset of Full Analysis Set entering the re-treatment phase.....................351
Table 14.3.1-4.5.4 Frequent [1] Serious adverse events incidence, regardless of study 
drug relationship  occurring during TFR phase by system organ class and 
preferred term - overall and maximum grade 3/4  – Subset of Full Analysis 
Set entering the TFR phase..................................................................................351
Table 14.3.1-4.6.1 Serious treatment-emergent adverse events incidence, suspected 
to be study drug related, by system organ class and preferred term during pre-
randomization Induction/consolidation phase  – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................352
Table 14.3.1-4.6.2 Serious treatment-emergent adverse events occurence, suspected 
to be study drug related, by system organ class and preferred term during pre-
randomization Induction/consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................352
Table 14.3.1-4.7.1 Serious treatment-emergent adverse events incidence, suspected 
to be study drug related, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................353
Table 14.3.1-4.7.2 Serious treatment-emergent adverse events occurrence, suspected 
to be study drug related, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................353
Table 14.3.1-4.8.1 Serious treatment-emergent adverse events incidence, suspected 
to be study drug related, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................353
Table 14.3.1-4.8.2 Serious treatment-emergent adverse events occurrence, suspected 
to be study drug related, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................353
Table 14.3.1-4.9.1 Serious adverse events incidence, suspected to be study drug 
related, by system organ class and preferred term during TFR phase – overall 
and maximum grade 3/4 – Subset of Full Analysis Set entering the TFR 
phase ....................................................................................................................353
Table 14.3.1-4.9.2 Serious adverse events occurrence, suspected to be study drug 
related, by system organ class and preferred term during TFR phase – overall 
and maximum grade 3/4 – Subset of Full Analysis Set entering the TFR 
phase ....................................................................................................................354


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Table 14.3.1-5.1.1 Treatment-emergent adverse events incidence leading to study 
drug discontinuation by system organ class and preferred term during pre-
randomization Induction/Consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................354
Table 14.3.1-5.1.2 Treatment-emergent adverse events occurence leading to study 
drug discontinuation by system organ class and preferred term during pre-
randomization Induction/Consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................355
Table 14.3.1-5.2.1 Treatment-emergent adverse events incidence leading to study 
drug discontinuation by system organ class and preferred term during post-
randomization phase (ARM 2) – overall and maximum grade 3/4 – Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................355
Table 14.3.1-5.2.2 Treatment-emergent adverse events occurrence leading to study 
drug discontinuation by system organ class and preferred term during post-
randomization phase (ARM 2)– overall and maximum grade 3/4 – Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................355
Table 14.3.1-5.3.1 Treatment-emergent adverse events incidence leading to study 
drug discontinuation by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................356
Table 14.3.1-5.3.2 Treatment-emergent adverse events occurrence leading to study 
drug discontinuation by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................356
Table 14.3.1-6.1.1 Treatment-emergent adverse events incidence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during pre-randomization Induction/ consolidation phase  – overall and 
maximum grade 3/4 –Full Analysis Set ..............................................................356
Table 14.3.1-6.1.2 Treatment-emergent adverse events occurrence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during pre-randomization Induction/consolidation phase – overall and 
maximum grade 3/4 –Full Analysis Set ..............................................................357
Table 14.3.1-6.2.1 Treatment-emergent adverse events incidence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during post-randomization consolidation phase (ARM 2) – overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ..........357
Table 14.3.1-6.2.2 Treatment-emergent adverse events occurrence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during post-randomization consolidation phase (ARM 2) – overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ..........357
Table 14.3.1-6.3.1 Treatment-emergent adverse events incidence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during re-treatment phase – overall and maximum grade 3/4 – Subset of 
Full Analysis Set entering the re-treatment phase...............................................358
Table 14.3.1-6.3.2 Treatment-emergent adverse events occurrence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 


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term during re-treatment phase – overall and maximum grade 3/4 – Subset of 
Full Analysis Set entering the re-treatment phase...............................................358
Table 14.3.1-6.4.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, by specific group and preferred term 
during Pre-randomization Induction/consolidation phase –by treatment arm, 
overall and maximum grade 3/4 – Full Analysis Set...........................................359
Table 14.3.1-6.4.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, by specific group and preferred term 
during Pre-randomization Induction/consolidation phase – by treatment arm, 
overall and maximum grade 3/4 –Full Analysis Set............................................360
Table 14.3.1-6.5.1 Treatment-emergent adverse events of interest incidence by 
specific group and preferred term during post-randomization consolidation 
phase (ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis 
Set randomized to Arm 2.....................................................................................361
Table 14.3.1-6.5.2 Treatment-emergent adverse events of interest occurrence, by  
specific group and preferred term during post-randomization consolidation 
phase (ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis 
Set randomized to Arm 2.....................................................................................362
Table 14.3.1-6.6.1 Treatment-emergent adverse events of interest incidence by 
specific group and preferred term during re-treatment phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment 
phase ....................................................................................................................363
Table 14.3.1-6.6.2 Treatment-emergent adverse events of interest occurrence by 
specific group and preferred term during re-treatment phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment 
phase ....................................................................................................................364
Table 14.3.1-6.7.1 Adverse events of interest incidence by specific group and 
preferred term during TFR phase – overall and maximum grade 3/4 – Subset 
of Full Analysis Set entering the TFR phase.......................................................364
Table 14.3.1-6.7.2 Adverse events of interest occurrence by specific group and 
preferred term during TFR phase – overall and maximum grade 3/4 – Subset 
of Full Analysis Set entering the TFR phase.......................................................364
Table 14.3.1-7.1.1 Treatment Emergent adverse events of interest incidence, 
regardless of study drug relationship, by specific group and preferred term 
and by cardiovascular risk factors during Pre-randomization 
Induction/consolidation phase – by treatment arm, overall and maximum 
grade 3/4 – Full Analysis Set...............................................................................365
Table 14.3.1-7.1.2 Treatment Emergent adverse events of interest occurrence, 
regardless of study drug relationship, by specific group and preferred term 
and by cardiovascular risk factors during Pre-randomization 
Induction/consolidation phase – by treatment arm, overall and maximum 
grade 3/4 –Full Analysis Set................................................................................366
Table 14.3.1-7.2.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 
cardiovascular risk factor– overall and maximum grade 3 or 4 – Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................367


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Table 14.3.1-7.2.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 
cardiovascular risk factor – overall and maximum grade 3 or 4 – Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................368
Table 14.3.1-7.3.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during re-treatment phase, by specific 
group and preferred term, and by cardiovascular risk factor – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................369
Table 14.3.1-7.3.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during re-treatment phase, by specific 
group and preferred term, and by cardiovascular risk factor – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................370
Table 14.3.1-7.4.1 Adverse events of interest incidence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
cardiovascular risk factor – Subset of Full Analysis Set entering the TFR 
phase ....................................................................................................................371
Table 14.3.1-7.4.2 Adverse events of interest occurrence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
cardiovascular risk factor – Subset of Full Analysis Set entering the TFR 
phase ....................................................................................................................371
Table 14.3.1-7.5.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during pre-randomization 
Induction/consolidation phase, by specific group and preferred term and by 4 
cardiovascular risk factors – overall and maximum grade 3/4  –Full Analysis 
Set ........................................................................................................................372
Table 14.3.1-7.5.2 Treatment-emergent adverse events of interest occurence, 
regardless of study drug relationship, during pre-randomization 
Induction/consolidation phase, by specific group and preferred term and by 4 
cardiovascular risk factors – overall and maximum grade 3/4 –Full Analysis 
Set ........................................................................................................................372
Table 14.3.1-7.6.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 4 
categories of cardiovascular risk factors– overall and maximum grade 3 or 4 
– Subset of Full Analysis Set randomized to Arm 2 ...........................................372
Table 14.3.1-7.6.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 4 
categories of cardiovascular risk factors – overall and maximum grade 3 or 4 
– Subset of Full Analysis Set randomized to Arm 2 ...........................................372
Table 14.3.1-7.7.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during re-treatment phase, by specific 
group and preferred term, and by 4 categories of cardiovascular risk factors –
Subset of Full Analysis Set entering the re-treatment phase...............................373
Table 14.3.1-7.7.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during re-treatment phase, by specific 


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group and preferred term, and by 4 categories of cardiovascular risk factors–
Subset of Full Analysis Set entering the re-treatment phase...............................373
Table 14.3.1-7.8.1 Adverse events of interest incidence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
4 categories of cardiovascular risk factors – Subset of Full Analysis Set 
entering the TFR phase........................................................................................374
Table 14.3.1-7.8.2 Adverse events of interest occurrence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
4 categories of cardiovascular risk factors– Subset of Full Analysis Set 
entering the TFR phase........................................................................................374
Table 14.3.1-9.1 On treatment deaths, by system organ class and preferred term 
during pre-randomization Induction/Consolidation phase - Safety Set...............375
Table 14.3.1-9.2 On treatment deaths, by system organ class and preferred term 
during post-randomization consolidation phase (ARM 2) – Subset of Safety 
Set randomized to Arm 2.....................................................................................376
Table 14.3.1-9.3  On treatment deaths, by system organ class and preferred term 
during re-treatment phase – Subset of Safety Set entering the re-treatment 
phase ....................................................................................................................376
Table 14.3.1-10.1.1 Cardiac and vascular adverse events of interest, incidence, by 
treatment arm during the pre-randomization induction/consolidation phase -
Full Analysis Set..................................................................................................377
Table 14.3.1-10.1.2 Cardiac and vascular adverse events of interest, occurence, by 
treatment arm during the pre-randomization induction/consolidation phase -
Full Analysis Set..................................................................................................379
Table 14.3.1-10.2.1 Cardiac and vascular adverse events of interest incidence, during 
the post-randomization consolidation phase (ARM 2) - Subset of Full 
Analysis Set randomized to Arm 2......................................................................380
Table 14.3.1-10.2.2 Cardiac and vascular adverse events of interest occurrence, 
during the post-randomization consolidation phase (ARM 2) - Subset of Full 
Analysis Set randomized to Arm 2......................................................................381
Table 14.3.1-10.3.1 Cardiac and vascular adverse events of interest, incidence, by 
treatment arm during the re-treatment phase – Subset of Full Analysis Set 
entered re-treatment phase...................................................................................381
Table 14.3.1-10.3.2 Cardiac and vascular adverse events of interest, occurence, by 
treatment arm during the re-treatment phase - Subset of Full Analysis Set 
entered re-treatment phase...................................................................................382
Table 14.3.1-10.4.1 Cardiac and vascular adverse events of interest, incidence, by 
treatment arm during the TFR phase – Subset of Full Analysis Set entered 
TFR phase............................................................................................................383
Table 14.3.1-10.4.2 Cardiac and vascular adverse events of interest, occurence, by 
treatment arm during the TFR phase - Subset of Full Analysis Set entered 
TFR phase............................................................................................................383
Table 14.3.1-10.5 Relationship between cardiac and vascular adverse events of 
interest with total cholesterol values - Full Analysis Set.....................................384
Table 14.3.1-10.6 Relationship between cardiac and vascular adverse events of 
interest with glycemic values - Full Analysis Set................................................385


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Table 14.3.1-11.1.1 Kaplan-Meier estimate of time-to-first CVEs during the pre-
randomization induction/consolidation phase – Full analysis set........................386
Table 14.3.1-11.1.2 Kaplan-Meier estimate of time-to-first CVEs during the post-
randomization consolidation phase (ARM 2)– Subset of Full Analysis Set 
patients randomized on Arm 2.............................................................................389
Table 14.3.1-11.2 Kaplan-Meier estimate of time-to-first CVEs during the re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase..390
Table 14.3.1-12.1 Medical history by system organ class and preferred term- Full 
Analysis Set .........................................................................................................391
Table 14.3.1-13.1 Prior exposure to imatinib before screening, MMR, age, and Sokal 
by LSC detection category - LSC sub-study Full Analysis Set...........................392
Table 14.3.1-13.2.1 Percentage from total CD34+ cells, CD34+/CD38+ cells -
Subgroup of LSC sub-study Full Analysis Set, LSC detected ............................393
Table 14.3.1-13.2.2 Percentage from total CD34+ cells, CD34+/CD38- cells -
Subgroup of LSC sub-study Full Analysis Set, LSC detected ............................394
Table 14.3.1-13.2.3 Percentage from total CD34+ cells, Immunophenotypically 
aberrant CD34+ cells - Subgroup of LSC sub-study Full Analysis Set, LSC 
detected................................................................................................................394
Table 14.3.1-13.2.4 Percentage from total CD34+ cells, Immunophenotypically 
aberrant CD34 negative cells - Subgroup of LSC sub-study Full Analysis Set, 
LSC detected........................................................................................................395
Table 14.3.1-13.3.1 Percentage of Ph+ cells, CD34+/CD38- cells - Subgroup of LSC 
sub-study Full Analysis Set, LSC detected..........................................................395
Table 14.3.1-13.3.2 Percentage of Ph+ cells, CD34+/CD38- cells - Subgroup of LSC 
sub-study Full Analysis Set, LSC detected..........................................................395
Table 14.3.1-13.3.3 Percentage of Ph+ cells, Immunophenotypically aberrant CD34+ 
cells - Subgroup of LSC sub-study Full Analysis Set, LSC detected..................395
Table 14.3.1-13.3.4 Percentage of Ph+ cells, Immunophenotypically aberrant CD34 
negative cells - Subgroup of LSC sub-study Full Analysis Set, LSC detected...395
Table 14.3.1-13.4 Total Percentage of CD34+ cells- Subgroup of LSC sub-study Full 
Analysis Set, LSC detected..................................................................................395
Table 14.3.1-13.5 LSC detection - LSC sub-study Full Analysis Set.............................396
Section 14.3.2 – Listings of deaths, other serious and significant adverse events..........397
Listing 14.3.2-1.1 Listing of deaths – Full Analysis Set.................................................397
Listing 14.3.2-1.2 Listing of deaths SDV sensitivity – Full Analysis Set.......................397
Listing 14.3.2-2.1    Listing of adverse events of special interest – Full Analysis Set....398
Listing 14.3.2-2.2   Listing of adverse events leading to study drug discontinuation –
Full Analysis Set..................................................................................................398
Listing 14.3.2-2.3   Listing of adverse events leading to study drug discontinuation 
during re-treatment phase – Subset of Full Analysis Set entering the re-
treatment period...................................................................................................399
Section 14.3.3 – Narratives of deaths, other serious and significant adverse 
events (non statistics and programming deliverables) ........................400
Section 14.3.4 – Abnormal laboratory value listings ......................................................400


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Listing 14.3.4-1.1   Listing of abnormal hematology laboratory value – Full Analysis 
Set ........................................................................................................................400
Listing 14.3.4-2.1   Listing of abnormal biochemistry laboratory value – Full 
Analysis Set .........................................................................................................400
Section 16 – Appendices .................................................................................................401
Section 16.1 – Study information........................................................................401
Section 16.1.6 – Listing of patients receiving test drug(s)/investigational 
product(s) from specific batches where more than one batch was 
used .....................................................................................................401
Section 16.1.7 – Randomization scheme and codes (subject identification and 
treatment assigned)..............................................................................402
Listing 16.1.7-1.1 Randomization schemes - Randomized patients ...............................402
Section 16.1.9 – Documentation of statistical methods.......................................403
Listing 16.1.9.1 Raw Statistical output from Demographic and characteristics at 
baseline– Full Analysis Set..................................................................................404
Listing 16.1.9.1.1 Raw Statistical output from Demographic and characteristics at 
baseline– LSC sub-study Full Analysis Set.........................................................404
Listing 16.1.9.2 Raw Statistical output from History of prior Imatinib therapy – Full 
Analysis Set .........................................................................................................404
Listing 16.1.9.2.1 Raw Statistical output from History of prior Imatinib therapy –
LSC sub-study Full Analysis Set.........................................................................404
Listing 16.1.9.3    Raw Statistical output from Cardiovascular risk factors at baseline 
– Full Analysis Set...............................................................................................405
Listing 16.1.9.4.1   Raw Statistical output from Molecular response MR4.0 at 12 
months of TFR–Subset of Full Analysis Set entering the TFR phase.................405
Listing 16.1.9.4.2   Raw Statistical output from Molecular response MR4.0 at 12 
months of TFR–Subset of Per Protocol Analysis Set entering the TFR phase ...405
Listing 16.1.9.5.1   Raw Statistical output from Kaplan-Meier analysis of treatment-
free survival during the TFR phase – Subset of Full Analysis Set entering the 
TFR phase............................................................................................................406
Listing 16.1.9.5.2   Raw Statistical output from Kaplan-Meier analysis of treatment-
free survival during the TFR phase – Subset of Per Protocol Analysis Set 
entering the TFR phase........................................................................................406
Listing 16.1.9.5.3   Raw Statistical output from Kaplan-Meier analysis of overall 
survival from Randomization–Randomized Set..................................................406
Listing 16.1.9.5.4   Raw Statistical output from Kaplan-Meier analysis of 
progression-free survival during the TFR phase – Subset of Full Analysis Set 
entering the TFR phase........................................................................................406
Listing 16.1.9.6.1   Raw Statistical output from Kaplan-Meier estimate of time-to-
first CVEs during the pre-randomization induction/consolidation phase – Full 
analysis set...........................................................................................................407
Listing 16.1.9.6.2   Raw Statistical output from Kaplan-Meier estimate of time-to-
first CVEs during the post-randomization consolidation phase (ARM 2)–
Subset of Full Analysis Set patients randomized on Arm 2................................407


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Listing 16.1.9.6.3   Raw Statistical output from Kaplan-Meier estimate of time-to-
first CVEs during the re-treatment phase – Subset of Full Analysis Set 
entering the re-treatment phase............................................................................407
Section 16.2 – Patient data listings..................................................................................409
Listing 16.2-1.1 Enrolled patients ...................................................................................409
Section 16.2.1 – Discontinued subjects...........................................................................410
Listing 16.2.1-1.1 Treatment and study completion - Safety Set....................................410
Listing 16.2.1-1.2 Study discontinuation – Full Analysis Set.........................................411
Listing 16.2.1-1.3
Screen failures (All subjects enrolled) ............................................412
Section 16.2.2 – Protocol deviations...............................................................................413
Listing 16.2.2-1.1 Protocol deviations – Enrolled patients .............................................413
Section 16.2.3 – Patients excluded from the efficacy analysis........................................414
Listing 16.2.3-1.1 Analysis set –  All patients ................................................................414
Section 16.2.4 – Demographics and data at screening....................................................415
Listing 16.2.4-1.1 Demographic data – Full Analysis Set ..............................................415
Listing 16.2.4-2.1 Family history – Full Analysis Set ....................................................415
Listing 16.2.4-2.2 Disease history– Full Analysis Set ....................................................416
Listing 16.2.4-3.1 Disease history I– Full Analysis Set..................................................417
Listing 16.2.4-3.2   Disease history II– Full Analysis Set...............................................418
Listing 16.2.4-3.3   Medical history/current medical condition – Full Analysis Set ......418
Listing 16.2.4.4    Cardiovascular risk factors at baseline for patients with not 
evaluable CV risk factor, Full Analysis Set.........................................................419
Section 16.2.5 – Compliance and/or drug concentration data if available (including 
Bioanalytical Data Report) ..................................................................................420
Listing 16.2.5-1.1 Dosage administration records – Full Analysis Set...........................420
Section 16.2.6 – Individual efficacy response data.........................................................420
Listing 16.2.6-1.1 BCR-ABL(IS) ratio and molecular responses during 
Induction/Consolidation and post-randomization consolidation phase (ARM 
2) – Full Analysis Set ..........................................................................................420
Listing 16.2.6-1.2 BCR-ABL(IS) ratio and molecular responses during TFR phase –
Subset of Full Analysis Set entering the TFR phase ...........................................421
Listing 16.2.6-1.3 BCR-ABL(IS) ratio and molecular responses during re-treatment 
phase – Subset of Full Analysis Set entering the re-treatment phase..................421
Listing 16.2.6-2.1 Criteria of successful TFR – Subset of Full Analysis Set entering 
the TFR phase......................................................................................................422
Listing 16.2.6-3.1 Assessment of progression-free survival during the TFR phase –
Subset of Full Analysis Set entering the TFR phase ...........................................423
Listing 16.2.6-3.2 Assessment of treatment-free survival during the TFR phase –
Subset of Full Analysis Set entering the TFR phase ...........................................424
Listing 16.2.6-3.3 Assessment of overall survival From Randomization –
Randomized set....................................................................................................425


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Listing 16.2.6-3.4 Assessment of relapse and treatment status during the TFR phase 
–Subset of Full Analysis Set entering the TFR phase and relapsed ....................426
Listing 16.2.6-4.1    WBC and molecular response in patients with WBC increase 
(CTCAE grade>G1) – Full Analysis Set.............................................................427
Listing 16.2.6-5.1   Individual Efficacy data, Molecular response – Full Analysis Set..428
Listing 16.2.6-5.2   Individual Efficacy data, Bone-marrow I – Full Analysis Set.........429
Listing 16.2.6-5.3   Individual Efficacy data, Bone -marrow II – Full Analysis Set ......430
Listing 16.2.6-6.1.1 Total percentage of CD34+ cells – LSC sub-study Full Analysis 
Set ........................................................................................................................431
Listing 16.2.6-6.2.1 Percentage of cells from total CD34 positive– LSC sub-study 
Full Analysis Set..................................................................................................432
Listing 16.2.6-6.3.1 Number of events sorted– LSC sub-study Full Analysis Set .........433
Listing 16.2.6-6.4.1 Ph+ by HIS– LSC sub-study Full Analysis Set..............................434
Listing 16.2.6-6.5.1 BCR-ABL by RT-PCR– LSC sub-study Full Analysis Set............435
Section 16.2.7 – Adverse event listings...........................................................................436
Listing 16.2.7-1.1 All adverse events – Full Analysis Set ..............................................436
Listing 16.2.7-2.1 Serious adverse events Full Analysis Set ..........................................437
Listing 16.2.7-2.2 Adverse events leading to study drug discontinuation – Full 
Analysis Set .........................................................................................................438
Listing 16.2.7-2.3 Adverse events of interest – Full Analysis Set ..................................439
Listing 16.2.7-3.1 CV risk factors, Nilotinib exposure, glucose and total cholesterol 
rates for patients with cardiac and vascular adverse events of interest, Full 
Analysis Set .........................................................................................................440
Listing 16.2.7-3.2 Cardiac and vascular adverse events of interest, Full Analysis Set...441
Listing 16.2.7-3.3 Outcomes and subsequent concomitant medications for patients 
with cardiac adverse events of interest, Full Analysis Set...................................443
Listing 16.2.7-3.4 Outcomes and subsequent concomitant medications for patients 
with vascular adverse events of interest, Full Analysis Set.................................444
Section 16.2.8 – Laboratory measurements ....................................................................445
Listing 16.2.8-1.1  Hematology laboratory values and normal ranges – Full Analysis 
Set ........................................................................................................................445
Listing 16.2.8-2.1 Biochemistry laboratory values and normal ranges – Full Analysis 
Set ........................................................................................................................446
Listing 16.2.8-3.1 Hematological data and molecular response in patients with 
absolute blasts higher than normal ranges, Full Analysis Set .............................448
Listing 16.2.8-3.2 Hematological data and molecular response in patients with 
absolute metamyelocytes higher than normal ranges, Full Analysis Set.............449
Section 16.2.9 – Vital signs, physical findings and other observations related to 
safety listings .......................................................................................................450
Listing 16.2.9-1.1    Vital signs – Full Analysis Set........................................................450
Listing 16.2.9-2.1    Electrocardiograms – Full Analysis Set..........................................451
Listing 16.2.9-2.2    Echocardiography – Full Analysis Set............................................451


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Listing 16.2.9-3.1    Concomitant medications – Full Analysis Set................................452
Listing 16.2.9- 3.2   Prohibited concomitant medications – Full Analysis Set...............452
Listing 16.2.9-4.1     Prior Imatinib therapy– Full Analysis Set .....................................453
Listing 16.2.9-4.2     Prior antineoplastic therapy, other than Imatinib – Full Analysis 
Set ........................................................................................................................453
Listing 16.2.9-5.1    Survival follow-up– Full Analysis set ............................................454
Listing 16.2.9-5.2    Safety follow-up– Full Analysis set................................................455
Listing 16.2.9-6    Prior imatinib exposure – LSC sub-study Full Analysis Set .............456


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1. General guidance
1.1
Document headers
The following header will be used for all tables, listings and figures in sections 14 and 16 
outlined in this document:  CAMN107AIC05.
1.2
Rules of presentation
Programming rules for tables and listings are described as follows. 

Add one space between a number and before the opening parenthesis and no spaces 
within the parenthesis e.g. ‘xx (xx.x)’ not ‘xx( xx.x)’.

There should be no spaces between a symbol and a number e.g. ‘<XX’ and not 
‘< XX’. A space is recommended between a special character and a number in order for 
a printout to print correctly, e.g. ‘≥ XX’ instead of ‘≥XX’.

There should be no ‘%’ sign after a result in any data cell. The ‘n (%)’ should appear 
once in the column header or in the first column next to the variable name. If result = 0, 
then there should be no parenthesis with zero percentage only a zero e.g. ‘0’ and not ‘0 
(0.0)’. The same holds for estimates and their CIs when they are not estimable (NE), 
they should be presented as ‘NE’ and not ‘NE (NE, NE)’.

Confidence intervals (CI) are provided in parenthesis, separated by a coma and a space 
after e.g. ‘(xx.x, xx.x)’.

All categorical data will be summarized by frequencies and percentages. Where 
categorical data is missing, a ‘Missing’ row will be included at the bottom with 
frequencies also presented. 

Decimal places will be as follows:
o
3 decimal places for p-values; if p-value is less than 0.001, it will be displayed 
as <0.001.
o
1 decimal place more than the original data is recorded to for means, medians 
and percentiles.
o
Two decimal places more for standard errors and standard deviations.
o
The same precision for minimums and maximums.
o
Frequency distribution: % has 1 decimal place.
o
Confidence intervals are given with the same number of decimal places as for 
the associated estimate.
o
If percentage = 100, no decimal is required and no percentage will be displayed 
if the frequency count is zero.

Default summary statistics for a continuous variable include n, mean, median, standard 
deviation, 25th and 75th percentiles. For CSR outputs min and max are optional and have 
only been displayed if needed.

For all laboratory parameters, ‘SI’ unit is used.

For AE tables, the preferred term will be sorted by descending frequency, unless 
indicated otherwise.

All listings will be sorted by country, center, patient number and visit/ event date.


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
Partial dates (day and/or month missing) will be listed as partial (not missing), unless 
the date has been imputed, in which case then the imputed date will be listed and flagged.

AE listings: when AE end date is missing, i.e., AE continued at final examination, 
“continuing” should be listed as the AE end date in the listings.

Day is relative to ‘day 1’ (defined above) and is calculated as: date of interest – ‘Day 1’ 
date + 1. For visits/events occurring prior to Day 1 the ‘+1’ will be excluded, so the day 
before Day 1 is Day -1.

Variables in days will be converted to different time unit if necessary, using following 
conversion rule.
-
1 month = 30.4375 days
-
year = 365.25 days
1.3
Document headers
The following header will be considered as standard for all CSR tables, listings and figures 
outlined in this document: 
CAMN107AIC05 – UNBLINDED – ANALYSIS CUT-OFF/ DBL DATE: DDMMMYYYY 
DRAFT/FINAL
…
Location/Program name – rundate
As the study is an open-label trial only one version of the tables, listings and figures will be 
produced.


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1.4
Presentation of table numbering and titles within this document
In order to facilitate the inclusion of a table of contents for all output, the format of the number 
and title for each layout should be in the Novstyle format “Non-TOC Heading” and therefore 
does not exactly match the layout that is intended for the final deliverable.
In practice, the numbering and title for all outputs defined in this document will be of the 
following formats respectively:
                            Table XX.X-X.X
Title Title Title Title Title Title
Population
Listing XX.X-X.X
Title Title Title Title Title Title
Population
1.5
Treatment group labels and ordering
The following treatment labels will be used for all tables, listings and figures in the order 
provided here:

ARM 1: the nilotinib 24 months treatment arm

ARM 2: the nilotinib 36 months treatment arm

Randomized (ARM 1 + ARM 2)

Not Randomized 
     
1.6
Distribution logistics

in-text tables/figures

Post-text tables/figures/listings

Appendix tables/figures/listings


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2. Overall table of contents for statistics and programming output
Tables, Listing Figures
Document History – Changes compared to previous version of RAP module 7.1 ....................2
1.
General guidance...............................................................................................................38
1.1
Document headers .................................................................................................38
1.2
Rules of presentation .............................................................................................38
1.3
Document headers .................................................................................................39
1.4
Presentation of table numbering and titles within this document..........................40
1.5
Treatment group labels and ordering.....................................................................40
1.6
Distribution logistics..............................................................................................40
2.
Overall table of contents for statistics and programming output ......................................41
Tables, Listing Figures .............................................................................................................41
3.
Shells and specification for CSR.......................................................................................75
3.1
Shells and specifications for sections 10 of the CSR (In-textText tables, 
listings and figures)................................................................................................75
Section 10........................................................................................................................109
Table 10-1 Analysis sets – All patients...........................................................................109
Table 10-2 Patient disposition during Induction/Consolidation phase and post-
Randomization Consolidation phase -Enrolled patients......................................110
Table 10-3 Demographic and characteristics at baseline – Full Analysis Set.................111
Table 10-4 Disease history – Full Analysis Set...............................................................113
Table 10-5 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation Safety Set .....................................................................116
Table 10-6 Duration of exposure to study treatment during post-randomization 
Consolidation phase (ARM 2) - Subset of Safety Set randomized to Arm 2......116
Table 11-1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................117
Table 11-2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................117
Table 11-3 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................117
Table 11-4 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................118
Table 11-5 Primary endpoint, Molecular response MR4.0 at 12 months of TFR 
phase–Subset of Full Analysis Set entering the TFR phase ................................118
Table 11-6 Secondary endpoint Kaplan-Meier analysis of treatment-free survival 
during the TFR phase – Subset of Full Analysis Set entering the TFR phase.....119
Table 11-7 Secondary endpoint, Molecular response 4.0 during post-randomization 
consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................120


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Table 11-8 Secondary endpoint, Kaplan-Meier analysis of overall survival from 
Randomization–Randomized Set.........................................................................121
Table 12-1 Overall summary of treatment-emergent adverse events occurring during 
pre-randomization Induction/consolidation phase – Full Analysis Set...............122
Table 12-2 Overall summary of treatment-emergent adverse events occurring during 
post-randomization consolidation phase (ARM 2) – Subset of Full Analysis 
Set randomized to Arm 2.....................................................................................123
Table 12-3 Overall summary of treatment-emergent adverse events occurring during 
re-treatment phase – Subset of Full Analysis Set entering the re-treatment 
phase ....................................................................................................................124
Table 12-4 Overall summary of adverse events occurring during TFR phase – Subset 
of Full Analysis Set entering the TFR phase.......................................................125
Table 12-5
Overall summary of frequent [1] treatment-emergent adverse 
events occurring during pre-randomization Induction/consolidation phase –
Full Analysis Set..................................................................................................126
Table 12-6 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during post-randomization Consolidation phase (ARM 2) – Subset 
of Full Analysis Set randomized to Arm 2..........................................................126
Table 12-7 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during re-treatment phase – Subset of Full Analysis Set entering 
the re-treatment phase..........................................................................................126
Table 12-8 Overall summary of frequent [1] adverse events occurring during TFR 
phase – Subset of Full Analysis Set entering the TFR phase ..............................126
Table 12-9 Serious treatment-emergent adverse events incidence, regardless of study 
drug relationship, by system organ class and preferred term during pre-
randomization Induction/consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................127
Table 12-10 Serious treatment-emergent adverse events incidence, regardless of 
study drug relationship, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................128
Table 12-11 Serious treatment-emergent adverse events incidence, regardless of 
study drug relationship, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................128
Table 12-12 Serious adverse events incidence, regardless of study drug relationship, 
by system organ class and preferred term during TFR phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase.......128
Table 12-13 Treatment-emergent adverse events of interest incidence, regardless of 
study drug relationship, by specific group and preferred term during Pre-
randomization Induction/consolidation phase –by treatment arm, overall and 
maximum grade 3/4 – Full Analysis Set..............................................................129
Table 12-14 Treatment-emergent adverse events of interest incidence by specific 
group and preferred term during post-randomization Consolidation phase 
(ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis Set 
randomized to Arm 2...........................................................................................130


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Table 12-15 Treatment-emergent adverse events of interest incidence by specific 
group and preferred term during re-treatment phase – overall and maximum 
grade 3/4 – Subset of Full Analysis Set entering the re-treatment phase............131
Table 12-16 Adverse events of interest incidence by specific group and preferred 
term during TFR phase – overall and maximum grade 3/4 – Subset of Full 
Analysis Set entering the TFR phase...................................................................131
Table 12-17 Treatment-emergent adverse events incidence leading to study drug 
discontinuation by system organ class and preferred term during pre-
randomization Induction/Consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................132
Table 12-18 Treatment-emergent adverse events incidence leading to study drug 
discontinuation by system organ class and preferred term during post-
randomizationphase (ARM 2) – overall and maximum grade 3/4 – Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................133
Table 12-19 On treatment deaths, by system organ class and preferred term during 
pre-randomization Induction/Consolidation phase - Safety Set ..........................133
Table 12-20 On treatment deaths, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – Subset of Safety Set 
randomized to Arm 2...........................................................................................134
Table 12-21 On treatment deaths, by system organ class and preferred term during 
re-treatment phase – Subset of Safety Set entering the re-treatment phase.........134
Listing 12-1 Listing of deaths – Full Analysis Set..........................................................135
Figure 11-1 Primary endpoint, Bar plot MR4.0 at 12 months of TFR phase –Subset 
of Full Analysis Set entering the TFR phase.......................................................136
Figure 11-2 Kaplan-Meier analysis of treatment-free survival during the TFR phase 
–Subset of Full Analysis Set entering the TFR phase .........................................137
3.2
Shells and specifications for Sections 14 and 16 of the CSR..............................138
Section 14 – tables, figures and graphs referred to but not included in the text .............138
Section 14.1 – Demographic data....................................................................................138
Table 14.1-1.1 Enrollment by country and center – All patients ....................................139
Table 14.1-1.2 Randomization by country and center – Randomized patients...............140
Table 14.1-1.3
Patient disposition (Screening failures), All patients..........................141
Table 14.1-2.1 Patient disposition during Induction/Consolidation phase and post-
Randomization Consolidation phase -Enrolled patients......................................143
Table 14.1-2.2 Patient disposition in each randomized arm – Full Analysis Set............144
Table 14.1-2.2.1 Patient disposition – Enrolled patients in LSC substudy.....................147
Table 14.1-2.3 Analysis sets –All patients......................................................................148
Table 14.1-2.4 Not Randomized patients - Enrolled patients .........................................149
Table 14.1-2.5   Patient disposition, Overall and by year-phase -Enrolled patients .......150
Table 14.1-2.6 Patients discontinued and reason for discontinuation – Full Analysis 
Set ........................................................................................................................154
Table 14.1-2.6.1 Patients discontinued and reason for discontinuation, SDV 
sensitivity – Full Analysis Set .............................................................................156


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Table 14.1-2.7 Summary of TFR phase – Full Analysis Set...........................................157
Table 14.1-2.7.1 Summary of TFR phase, SDV sensitivity – Full Analysis Set ............158
Table 14.1-2.8    Summary of re-treatment phase – Full Analysis Set............................159
Table 14.1-2.8.1 Summary of re-treatment phase, SDV sensitivity – Full Analysis 
Set ........................................................................................................................160
Table 14.1-2.9 Summary of patients with relapse during the TFR phase but no 
entering re-treatment phase –-Subset of Full Analysis Set entering the TFR 
phase ....................................................................................................................161
Table 14.1-3.1 Demographic and characteristics at baseline– Full Analysis Set............163
Table 14.1-3.1.1 Demographic and characteristics at baseline– LSC sub-study Full 
Analysis Set .........................................................................................................166
Table 14.1-4.1 Disease history – Full Analysis Set.........................................................167
Table 14.1-4.1.1 Disease history – LSC sub-study Full Analysis Set.............................170
Table 14.1-5.1 History of prior Imatinib therapy – Full Analysis Set ............................171
Table 14.1-5.1.1 History of prior Imatinib therapy – LSC sub-study Full Analysis Set.172
Table 14.1-5.2 Prior antineoplastic therapy, other than Imatinib, by ATC class and 
preferred term -  Full Analysis Set ......................................................................173
Table 14.1-6.1 Cardiovascular risk factors at baseline – Full Analysis Set....................174
Table 14.1-6.2 Cardiovascular risk factors (based on medical history, laboratory 
values and vital signs at baseline) – Full Analysis Set........................................175
Section 14.2 – Efficacy and other non-safety data (e.g. PK, PK/PD, Health Econ., 
QoL).....................................................................................................................177
Figure 14.2-1.1 Box-plot of BCR-ABL ratio (IS) during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................178
Figure 14.2-1.2 Box-plot of BCR-ABL ratio (IS) during post-randomization 
Consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
ARM 2 .................................................................................................................179
Figure 14.2-1.3 Box-plot of BCR-ABL ratio (IS) during TFR phase – Subset of Full 
Analysis Set entered TFR....................................................................................179
Figure 14.2-1.4 Box-plot of BCR-ABL ratio (IS) during re-treatment phase – Subset 
of Full Analysis Set entered re-treatment ............................................................179
Figure 14.2-1.5 Box-plot of BCR-ABL ratio (IS) during TFR phase – , SDV 
sensitivity Subset of Full Analysis Set entered TFR ..........................................180
Figure 14.2-1.6 Box-plot of BCR-ABL ratio (IS) during re-treatment phase, SDV 
sensitivity –Subset of Full Analysis Set entered re-treatment............................180
Figure 14.2-2.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase - Full Analysis Set .............................................181
Figure 14.2-2.1.2 Raw cumulative incidence of MMR during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
ARM 2 .................................................................................................................181
Figure 14.2-2.2.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio - Full 
Analysis Set .........................................................................................................182


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Figure 14.2-2.2.2 Raw cumulative incidence of MMR during post-randomization 
Consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to ARM 2.............................................182
Figure 14.2-2.3.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................183
Figure 14.2-2.3.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
ARM 2 .................................................................................................................183
Figure 14.2-2.3.11 Raw cumulative incidence of MR 4.0, Randomized vs Not 
Randomized, during pre-randomization Induction/Consolidation phase - Full 
Analysis Set .........................................................................................................184
Figure 14.2-2.4.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio - Full 
Analysis Set .........................................................................................................184
Figure 14.2-2.4.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to ARM 2.............................................185
Figure 14.2-2.5.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set .............................................185
Figure 14.2-2.5.11 Raw cumulative incidence of MR 4.5, Randomized vs Not 
Randomized, during pre-randomization Induction/Consolidation phase- Full 
Analysis Set .........................................................................................................185
Figure 14.2-2.5.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
ARM 2 .................................................................................................................185
Figure 14.2-2.6.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio - Full 
Analysis Set .........................................................................................................185
Figure 14.2-2.6.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to ARM 2.............................................186
Figure 14.2-2.7.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline..................................................................................................186
Figure 14.2-2.8.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching MR 
4.0 at baseline ......................................................................................................186
Figure 14.2-2.9.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching MR 
4.5 at baseline ......................................................................................................186
Figure 14.2-2.9.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Induction/Consolidation phase (ARM 2)- Subset of Full Analysis Set patients 
not reaching MR 4.5 at baseline, randomized to ARM 2....................................186
Figure 14.2-2.10.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set .........................................................................................................187


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Figure 14.2-2.10.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) by BCR-ABL(IS) ratio at baseline - Subset of 
Full Analysis Set randomized to ARM 2.............................................................187
Figure 14.2-2.11.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set .........................................................................................................188
Figure 14.2-2.11.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) by BCR-ABL(IS) ratio at baseline - Subset of 
Full Analysis Set randomized to ARM 2.............................................................188
Figure 14.2-2.12.1 Box-plot of BCR-ABL ratio (IS) during pre-randomization 
Induction/Consolidation phase, excluding outliers (BCR-ABL (IS) ratio>10 -
Full Analysis Set..................................................................................................189
Figure 14.2-2.12.2 Box-plot of BCR-ABL ratio (IS) over post-randomization 
Consolidation phase (ARM 2), excluding outliers (BCR-ABL (IS) ratio>10 -
Subset of Full Analysis Set randomized to ARM 2.............................................189
Figure 14.2-13.1 Raw cumulative incidence of loss of MMR during TFR – Subset of 
Full Analysis Set entering the TFR phase ...........................................................191
Figure 14.2-13.2 Raw cumulative incidence of MMR during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................191
Figure 14.2-13.3 Raw cumulative incidence of loss of MMR during TFR, SDV 
sensitivity – Subset of Full Analysis Set entering the TFR phase.......................192
Figure 14.2-13.4 Raw cumulative incidence of MMR during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase..192
Figure 14.2-14.1 Raw cumulative incidence of loss of MR4.0 during TFR phase –
Subset of Full Analysis Set entering the TFR phase ...........................................192
Figure 14.2-14.2 Raw cumulative incidence of MR4.0 during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................192
Figure 14.2-14.3 Raw cumulative incidence of loss of MR4.0 during TFR phase, 
SDV sensitivity –Subset of Full Analysis Set entering the TFR phase...............193
Figure 14.2-14.4 Raw cumulative incidence of MR4.0 during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase..193
Figure 14.2-15.1 Raw cumulative incidence of loss of MR4.5 during TFR phase –
Subset of Full Analysis Set entering the TFR phase with MR4.5.......................193
Figure 14.2-15.2 Raw cumulative incidence of MR4.5 during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................193
Figure 14.2-15.3 Raw cumulative incidence of loss of MR4.5 during TFR phase, 
SDV sensitivity – Subset of Full Analysis Set entering the TFR phase with 
MR4.5..................................................................................................................194
Figure 14.2-15.4 Raw cumulative incidence of MR4.5 during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase..194
Figure 14.2-16 Bar plot MR4.0 at 12 months of TFR phase –Subset of Full Analysis 
Set entering the TFR phase..................................................................................195
Figure 14.2-16.2 Bar plot MR4.0 at month 12 TFR phase , SDV sensitivity –Subset 
of Full Analysis Set entering the TFR phase.......................................................195


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Figure 14.2-17.1 Kaplan-Meier analysis of progression-free survival during the TFR 
phase –Subset of Full Analysis Set entering the TFR phase ...............................196
Figure 14.2-17.2 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase –Subset of Full Analysis Set entering the TFR phase ...............................196
Figure 14.2-17.3 Kaplan-Meier analysis of progression-free survival during the TFR 
phase, SDV sensitivity –Subset of Full Analysis Set entering the TFR phase....197
Figure 14.2-17.4 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase, SDV sensitivity –Subset of Full Analysis Set entering the TFR phase....197
Figure 14.2-18.1 Kaplan-Meier analysis of reachievement of MMR, after loss of 
response in TFR –Subset of Full Analysis Set entering the re-treatment phase..197
Figure 14.2-18.2 Kaplan-Meier analysis of reachievement of MR4.0, after loss of 
response in TFR – Subset of Full Analysis Set entering the re-treatment phase.197
Figure 14.2-18.3 Kaplan-Meier analysis of reachievement of MMR, after loss of 
response in TFR, SDV sensitivity –Subset of Full Analysis Set entering the 
re-treatment phase................................................................................................198
Figure 14.2-18.4 Kaplan-Meier analysis of reachievement of MR4.0, after loss of 
response in TFR, SDV sensitivity – Subset of Full Analysis Set entering the 
re-treatment phase................................................................................................198
Table 14.2-1.1 Description of BCR-ABL (IS) ratio at Month 3 and halving time of 
BCR-ABL (IS) ratio subgroups – Full Analysis Set ...........................................199
Table 14.2-2.1.1 Molecular response MR4.0 at 12 months of TFR–Subset of Full 
Analysis Set entering the TFR phase...................................................................200
Table 14.2-2.1.2 Molecular response MR4.0 at 12 months of TFR–Subset of Per 
Protocol Analysis Set entering the TFR phase ....................................................200
Table 14.2-2.1.3 Molecular response MR4.0 at 12 months of TFR–Full Analysis Set ..201
Table 14.2-2.1.4 Molecular response MR4.0 at 12 months of TFR–Per Protocol 
Analysis Set .........................................................................................................201
Table 14.2-2.1.5 Molecular response MR4.0 at 12 months of TFR– Subset of Full 
Analysis Set entering the TFR phase with MR4.0 achieved up to month 3 of 
pre-randomization Induction/Consolidation phase..............................................202
Table 14.2-2.1.6 Molecular response MR4.0 at 12 months of TFR– Subset of Full 
Analysis Set entering the TFR phase with MR4.5 achieved up to month 3 of 
pre-randomization Induction/Consolidation phase..............................................202
Table 14.2-2.1.7 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –
Subset of Full Analysis Set entering the TFR phase ...........................................202
Table 14.2-2.1.8 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –
Subset of Per Protocol Analysis Set entering the TFR phase..............................202
Table 14.2-2.1.9 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –
Full Analysis Set..................................................................................................202
Table 14.2-2.1.10 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity 
–Per Protocol Analysis Set ..................................................................................203
Table 14.2-2.2.1 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase – Subset of Full Analysis Set entering the TFR phase ..............................204


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Table 14.2-2.2.2 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase – Subset of Per Protocol Analysis Set entering the TFR phase.................205
Table 14.2-2.2.3 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase, SDV sensitivity – Subset of Full Analysis Set entering the TFR phase...205
Table 14.2-2.2.4 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase, SDV sensitivity – Subset of Per Protocol Analysis Set entering the 
TFR phase............................................................................................................205
Table 14.2-2.3 Kaplan-Meier analysis of overall survival from Randomization–
Randomized Set...................................................................................................206
Table 14.2-2.4 Kaplan-Meier analysis of progression-free survival during the TFR 
phase –- Subset of Full Analysis Set entering the TFR phase.............................207
Table 14.2-2.5 Kaplan-Meier analysis of overall survival from Randomization, SDV 
sensitivity –Randomized Set ...............................................................................208
Table 14.2-2.6 Kaplan-Meier analysis of progression-free survival during the TFR 
phase, SDV sensitivity –- Subset of Full Analysis Set entering the TFR phase .208
Table 14.2-3.1 Major molecular response during pre-randomization 
Induction/Consolidation phase –Full Analysis Set..............................................209
Table 14.2-3.1.1 Major molecular response during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................210
Table 14.2-3.2 Major molecular response during post-randomization consolidation 
phase (ARM 2)– Subset of Full Analysis Set randomized to Arm 2...................211
Table 14.2-3.2.1 Major molecular response during post-randomization consolidation 
phase (ARM 2) – LSC sub-study Full Analysis Set randomized to Arm 2.........211
Table 14.2-3.3 Major molecular response during TFR phase –Subset of Full Analysis 
Set patients entered TFR phase ...........................................................................212
Table 14.2-3.4 Major molecular response during re-treatment phase–Subset of Full 
Analysis Set patients entered re- treatment phase ...............................................213
Table 14.2-3.5 Major molecular response during TFR phase –Subset of Full Analysis 
Set patients entered TFR phase with MR4.0 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................214
Table 14.2-3.6 Major molecular response during TFR phase –Subset of Full Analysis 
Set patients entered TFR phase with MR4.5 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................214
Table 14.2-3.7 Major molecular response during TFR phase, SDV sensitivity –
Subset of Full Analysis Set patients entered TFR phase.....................................214
Table 14.2-3.8 Major molecular response during re-treatment phase, SDV sensitivity 
–Subset of Full Analysis Set patients entered re- treatment phase......................214
Table 14.2-4.1 Molecular response 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................215
Table 14.2-4.1.1 Molecular response 4.0 during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................215
Table 14.2-4.2.1 Molecular response 4.0 during post-randomization consolidation 
phase (ARM 2) – Subset of Full Analysis Set randomized to Arm 2..................215


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Table 14.2-4.2.2 Molecular response 4.0 during post-randomization consolidation 
phase (ARM 2) – Subset of  Per Protocol randomized to Arm 2 ........................215
Table 14.2-4.2.11 Molecular response 4.0 during post-randomization consolidation 
phase (ARM 2) – Subset of  LSC sub-study Full Analysis Set randomized to 
Arm 2...................................................................................................................215
Table 14.2-4.3.1 Molecular response 4.0 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase..................................................................................216
Table 14.2-4.3.2 Molecular response 4.0 during TFR phase – Subset of Per Protocol 
Analysis Set entering the TFR phase...................................................................216
Table 14.2-4.3.3 Molecular response 4.0 during TFR phase , SDV sensitivity –
Subset of Full Analysis Set entering the TFR phase ...........................................216
Table 14.2-4.4 Molecular response 4.0 during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................217
Table 14.2-4.5 Molecular response 4.0 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.0 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................217
Table 14.2-4.6 Molecular response 4.0 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.5 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................217
Table 14.2-4.7 Molecular response 4.0 during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase...............................217
Table 14.2-5.1 Molecular response 4.5 during pre-randomization 
Induction/Consolidation– Full Analysis Set........................................................218
Table 14.2-5.1.1 Molecular response 4.5 during pre-randomization 
Induction/Consolidation– LSC sub-study Full Analysis Set...............................218
Table 14.2-5.2 Molecular response 4.5 during post-randomization consolidation 
phase (ARM 2) – Subset of Full Analysis Set randomized to Arm 2..................218
Table 14.2-5.2.1 Molecular response 4.5 during post-randomization consolidation 
phase (ARM 2) – Subset of LSC sub-study Full Analysis Set randomized to  
Arm 2...................................................................................................................218
Table 14.2-5.3 Molecular response 4.5 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase..................................................................................218
Table 14.2-5.4 Molecular response 4.5 during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................218
Table 14.2-5.5 Molecular response 4.5 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.0 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................219
Table 14.2-5.6 Molecular response 4.5 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.5 achieved up to month 3 of pre-
randomization Induction/Consolidation phase ....................................................219
Table 14.2-5.7 Molecular response 4.5 during TFR phase, SDV sensitivity – Subset
of Full Analysis Set entering the TFR phase.......................................................219
Table 14.2-5.8 Molecular response 4.5 during re-treatment phase, SDV sensitivity  –
Subset of Full Analysis Set entering the re-treatment phase...............................219


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Table 14.2-6.1 Raw cumulative incidence MMR during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................220
Table 14.2-6.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................221
Table 14.2-6.2 Raw cumulative incidence MMR during post-randomization 
Consolidation phase (ARM 2)  - Subset of  Full Analysis Set patients 
randomized to ARM 2 .........................................................................................221
Table 14.2-6.2.1 Raw cumulative incidence MMR during post-randomization 
Consolidation phase (ARM 2)  - Subset of  LSC sub-study Fulls Anslysis Set 
randomized to ARM 2 .........................................................................................221
Table 14.2-6.3 Raw cumulative incidence of MMR during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................222
Table 14.2-6.4 Raw cumulative incidence of MMR during re-treatment phase , SDV 
sensitivity  – Subset of Full Analysis Set entering the re-treatment phase..........222
Table 14.2-7.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................222
Table 14.2-7.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................222
Table 14.2-7.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
ARM 2 .................................................................................................................223
Table 14.2-7.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) – Subset of LSC sub-study Full Analysis Set  
randomized to ARM 2 .........................................................................................223
Table 14.2-7.3 Raw cumulative incidence of MR 4.0 during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................223
Table 14.2-7.4 Raw cumulative incidence of MR 4.0 during re-treatment phase, SDV 
sensitivity  – Subset of Full Analysis Set entering the re-treatment phase..........223
Table 14.2-8.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................224
Table 14.2-8.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................224
Table 14.2-8.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................224
Table 14.2-8.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) - Subset of LSC sub-study Full Analysis Set 
randomized to Arm 2...........................................................................................224
Table 14.2-8.3 Raw cumulative incidence of MR 4.5 during re-treatment phase -
Subset of Full Analysis Set entering the re-treatment phase...............................224
Table 14.2-8.4 Raw cumulative incidence of MR 4.5 during re-treatment phase , 
SDV sensitivity - Subset of Full Analysis Set entering the re-treatment phase ..225
Table 14.2-9.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – Full 
Analysis Set .........................................................................................................226


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Table 14.2-9.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – LSC 
sub-study Full Analysis Set .................................................................................226
Table 14.2-9.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to Arm 2 ..............................................227
Table 14.2-9.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of LSC sub-study Full Analysis Set randomized to Arm 2 .....................228
Table 14.2-9.3 Raw cumulative incidence of MMR during re-treatment phase by 
halving time of BCR-ABL (IS) ratio – Subset of Full Analysis Set entering 
the re-treatment phase..........................................................................................228
Table 14.2-10.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – Full 
Analysis Set .........................................................................................................229
Table 14.2-.10.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – LSC 
sub-study Full Analysis Set .................................................................................229
Table 14.2-10.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to Arm 2 ..............................................229
Table 14.2-10.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of LSC sub-study Full Analysis Set randomized to Arm 2 .....................229
Table 14.2-10.3 Raw cumulative incidence of MR4.0 during re-treatment phase by 
halving time of BCR-ABL (IS) ratio – Subset of Full Analysis Set entering 
the re-treatment phase..........................................................................................229
Table 14.2-11.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – Full 
Analysis Set .........................................................................................................230
Table 14.2-.11.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – LSC 
sub-study Full Analysis Set .................................................................................230
Table 14.2-11.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to Arm 2 ..............................................230
Table14.2-11.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of LSC sub-study Full Analysis Set randomized to Arm 2 .....................230
Table 14.2-11.3 Raw cumulative incidence of MR4.5 during re-treatment phase by 
halving time of BCR-ABL (IS) ratio – Subset of Full Analysis Set entering 
the re-treatment phase..........................................................................................230
Table 14.2-12.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – Full 
Analysis Set .........................................................................................................231


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Table 14.2-12.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – LSC 
sub-study Full Analysis Set .................................................................................231
Table 14.2-12.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................231
Table 14.2-12.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
LSC sub-study Full Analysis Set randomized to Arm 2......................................232
Table 14.2-12.3 Raw cumulative incidence of MMR during re-treatment phase by 
BCR-ABL (IS) ratio at Month 3 – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................232
Table 14.2-13.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – Full 
Analysis Set .........................................................................................................233
Table 14.2-13.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – LSC 
sub-study Full Analysis Set .................................................................................233
Table 14.2-13.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................233
Table 14.2-13.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
LSC sub-study Full Analysis Set randomized to Arm 2......................................233
Table 14.2-13.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by 
BCR-ABL (IS) ratio at Month 3 – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................233
Table 14.2-14.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – Full 
Analysis Set .........................................................................................................234
Table 14.2-14.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – LSC 
sub-study Full Analysis Set .................................................................................234
Table 14.2-14.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................234
Table 14.2-14.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
LSC sub-study Full Analysis Set randomized to Arm 2......................................234
Table 14.2-14.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by 
BCR-ABL (IS) ratio at Month 3 – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................234
Table 14.2-15.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by Sokal Risk category– Full Analysis Set........235
Table 14.2-15.2 Raw cumulative incidence of MR4.0 during pre-randomization 
Induction/Consolidation phase by Sokal Risk category– Full Analysis Set........235


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Table 14.2-15.3 Raw cumulative incidence of MR4.5 during pre-randomization 
Induction/Consolidation phase by Sokal Risk category– Full Analysis Set........236
Table 14.2-16.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by time since initial diagnosis of CML– Full 
Analysis Set .........................................................................................................237
Table 14.2-16.2 Raw cumulative incidence of MR4.0 during pre-randomization 
Induction/Consolidation phase by time since initial diagnosis of CML – Full 
Analysis Set .........................................................................................................238
Table 14.2-16.3 Raw cumulative incidence of MR4.5 during pre-randomization 
Induction/Consolidation phase by time since initial diagnosis of CML – Full 
Analysis Set .........................................................................................................238
Table 14.2-17.1 Suboptimal response up to 24 months of pre-randomization 
Induction/Consolidation phase -  Full Analysis Set patients who prematurely 
discontinued the pre-randomization Induction/Consolidation phase ..................239
Table 14.2-17.2 Suboptimal response up to 12 months of post-randomization 
Consolidation phase (ARM 2)  - Subset of  Full Analysis Set patients who 
prematurely discontinued the Induction/Consolidation phase randomized to 
Arm 2...................................................................................................................240
Table 14.2-18.1 Suboptimal response up to 24 months of pre-randomization 
Induction/Consolidation phase - Full Analysis Set .............................................240
Table 14.2-18.2 Suboptimal response up to 12 months of post-randomization 
Consolidation phase - Subset of Full Analysis Set, randomized to ARM 2........240
Table 14.2-19.1 Kinetics of BCR-ABL (IS) ratio during pre-randomization 
Induction/Consolidation phase – Full Analysis Set.............................................241
Table 14.2-19.1.1 Kinetics of BCR-ABL (IS) ratio during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set....................241
Table 14.2-19.2 Kinetics of BCR-ABL (IS) ratio during post-randomization 
consolidation phase (ARM 2) –Subset of Full Analysis Set randomized to
Arm 2...................................................................................................................242
Table 14.2-19.2.1 Kinetics of BCR-ABL (IS) ratio during post-randomization 
consolidation phase (ARM 2) –Subset of LSC sub-study Full Analysis Set 
randomized to Arm 2...........................................................................................242
Table 14.2-19.3 Kinetics of BCR-ABL (IS) ratio during TFR phase – Subset of Full 
Analysis Set entering the TFR phase...................................................................243
Table 14.2-19.4 Kinetics of BCR-ABL (IS) ratio during re-treatment phase – Subset 
of Full Analysis Set entering the re-treatment phase...........................................245
Table 14.2-19.5 Kinetics of BCR-ABL (IS) ratio during TFR phase, SDV sensitivity   
– Subset of Full Analysis Set entering the TFR phase ........................................246
Table 14.2-19.6 Kinetics of BCR-ABL (IS) ratio during re-treatment phase , SDV 
sensitivity  – Subset of Full Analysis Set entering the re-treatment phase..........246
Table 14.2-20.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline..................................................................................................247


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Table 14.2-20.2 Raw cumulative incidence of MMR during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MMR at baseline, randomized to ARM 2.............................................247
Table 14.2-21.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching MR 
4.0 at baseline ......................................................................................................247
Table 14.2-21.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MR 4.0 at baseline, randomized to ARM 2 ..........................................247
Table 14.2-22.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase -   Full Analysis Set patients not reaching MR 
4.5 at baseline ......................................................................................................247
Table 14.2-22.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2)  - Subset of  Full Analysis Set patients not 
reaching MR 4.5 at baseline, randomized to ARM 2 ..........................................248
Table 14.2-22.3 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline..................................................................................................248
Table 14.2-22.4 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MMR at baseline, randomized to ARM 2.............................................248
Table 14.2-22.5 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline..................................................................................................248
Table 14.2-22.6 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MMR at baseline, randomized to ARM 2.............................................248
Table 14.2-23.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline -  Full 
Analysis Set .........................................................................................................249
Table 14.2-23.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at baseline– LSC sub-
study Full Analysis Set........................................................................................250
Table 14.2-23.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
Full Analysis Set, randomized to ARM 2............................................................250
Table 14.2-23.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................251
Table 14.2-23.3 Raw cumulative incidence of MMR during re-treatment phase by 
BCR-BL(IS) ratio at baseline – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................251
Table 14.2-24.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set .........................................................................................................252


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Table 14.2-24.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at baseline– LSC sub-
study Full Analysis Set........................................................................................252
Table 14.2-24.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
Full Analysis Set, randomized to ARM 2............................................................252
Table 14.2-24.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................252
Table 14.2-24.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by 
BCR-BL(IS) ratio at baseline – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................252
Table 14.2-25.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set .........................................................................................................253
Table 14.2-25.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at baseline– LSC sub-
study Full Analysis Set........................................................................................253
Table 14.2-25.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
Full Analysis Set, randomized to ARM 2............................................................253
Table 14.2-25.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................253
Table 14.2-25.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by 
BCR-BL(IS) ratio at baseline – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................253
Table 14.2-26.1 Raw cumulative loss of MMR during TFR phase –Subset of Full 
Analysis Set entering the TFR phase...................................................................254
Table 14.2-26.2 Raw cumulative loss of MR4.0 during TFR phase –Subset of Full 
Analysis Set entering the TFR phase...................................................................255
Table 14.2-26.3 Raw cumulative loss of MR4.5 during TFR phase –Subset of Full 
Analysis Set entering the TFR phase with MR4.5 ..............................................255
Table 14.2-26.4 Raw cumulative loss of MMR during TFR phase, SDV sensitivity  –
Subset of Full Analysis Set entering the TFR phase ...........................................256
Table 14.2-26.5 Raw cumulative loss of MR4.0 during TFR phase, SDV sensitivity 
–Subset of Full Analysis Set entering the TFR phase .........................................256
Table 14.2-26.6 Raw cumulative loss of MR4.5 during TFR phase, SDV sensitivity 
–Subset of Full Analysis Set entering the TFR phase with MR4.5.....................256
Table 14.2-27.1 Descriptive Statistics for CD34 cells: Total percentage – LSC sub-
study Full Analysis Set........................................................................................257
Table 14.2-28.1 Descriptive Statistics for CD34+/CD38+ cells: Percentage from 
total CD34+ cells – LSC sub-study Full Analysis Set.........................................259
Table 14.2-28.2 Descriptive Statistics for number of events sorted in CD34+/CD38+ 
cells – LSC sub-study Full Analysis Set..............................................................260


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Table 14.2-28.3 Ph+ by HIS status, in CD34+/CD38+ cells – LSC sub-study Full 
Analysis Set .........................................................................................................261
Table 14.2-28.4 Descriptive statistics of Ph+ in CD34+/CD38+ cells– LSC sub-study 
Full Analysis Set..................................................................................................261
Table 14.2-28.5 BCR-ABL by RT-PCR status, in CD34+/CD38+ cells – LSC sub-
study Full Analysis Set........................................................................................261
Table 14.2-29.1 Descriptive Statistics for CD34+/CD38- cells: Percentage from total 
CD34+ cells – LSC sub-study Full Analysis Set.................................................262
Table 14.2-29.2 Descriptive Statistics for number of events sorted in CD34+/CD38-
cells – LSC sub-study Full Analysis Set..............................................................262
Table 14.2-29.3 Ph+ by HIS status, in CD34+/CD38- cells – LSC sub-study Full 
Analysis Set .........................................................................................................262
Table 14.2-29.4 Descriptive statistics of Ph+ in CD34+/CD38- cells– LSC sub-study 
Full Analysis Set..................................................................................................262
Table 14.2-29.5 BCR-ABL by RT-PCR status, in CD34+/CD38- cells – LSC sub-
study Full Analysis Set........................................................................................262
Table 14.2-30.1 Descriptive Statistics for Immunophenotypically aberrant CD34+ 
cells: Percentage from total CD34+ cells –LSC sub-study Full Analysis Set.....263
Table 14.2-30.2 Descriptive Statistics for number of events sorted in 
Immunophenotypically aberrant CD34+ cells – LSC sub-study Full Analysis 
Set ........................................................................................................................263
Table 14.2-30.3 Ph+ by HIS status, in Immunophenotypically aberrant CD34+ cells 
– LSC sub-study Full Analysis Set......................................................................263
Table 14.2-30.4 Descriptive statistics of Ph+ in Immunophenotypically aberrant
CD34+ cells– LSC sub-study Full Analysis Set..................................................263
Table 14.2-30.5 BCR-ABL by RT-PCR status, in Immunophenotypically aberrant
CD34+ cells – LSC sub-study Full Analysis Set.................................................263
Table 14.2-31.1 Descriptive Statistics for Immunophenotypically aberrant CD34-
cells: Percentage from total CD34+ cells – LSC sub-study Full Analysis Set ..264
Table 14.2-31.2 Descriptive Statistics for number of events sorted in 
Immunophenotypically aberrant CD34- cells- LSC sub-study Full Analysis 
Set ........................................................................................................................264
Table 14.2-31.3 Ph+ by HIS status, in Immunophenotypically aberrant CD34- cells –
LSC sub-study Full Analysis Set.........................................................................264
Table 14.2-31.4 Descriptive statistics of Ph+ in Immunophenotypically aberrant 
CD34- cells– LSC sub-study Full Analysis Set...................................................264
Table 14.2-31.5 BCR-ABL by RT-PCR status, in Immunophenotypically aberrant 
CD34- cells – LSC sub-study Full Analysis Set..................................................264
Table 14.2-32.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by duration of prior exposure to Imatinib -  
Full Analysis Set..................................................................................................265
Table 14.2-32.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by by prior Imatib treatment duration – LSC 
sub-study Full Analysis Set .................................................................................266


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Table 14.2-32.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
Full Analysis Set, randomized to ARM 2............................................................266
Table 14.2-32.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................267
Table 14.2-32.3 Raw cumulative incidence of MMR during re-treatment phase by 
prior Imatib treatment duration – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................267
Table 14.2-33.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration - Full 
Analysis Set .........................................................................................................268
Table 14.2-33.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration – LSC sub-
study Full Analysis Set........................................................................................268
Table 14.2-33.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
Full Analysis Set, randomized to ARM 2............................................................268
Table 14.2-33.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................268
Table 14.2-33.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by 
prior Imatib treatment duration – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................268
Table 14.2-34.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration - Full 
Analysis Set .........................................................................................................269
Table 14.2-34.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration – LSC sub-
study Full Analysis Set........................................................................................269
Table 14.2-34.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
Full Analysis Set, randomized to ARM 2............................................................269
Table 14.2-34.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2.................................269
Table 14.2-34.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by 
prior Imatib treatment duration – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................269
Section 14.3 – Safety data ...............................................................................................271
Table 14.3-1.1 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation– Safety Set...................................................................271
Table 14.3-1.1.1 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation– LSC sub-study Safety Set ..........................................272


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Table 14.3-1.2 Duration of exposure to study treatment during post-randomization 
Consolidation phase (ARM 2) - Subset of Safety Set randomized to Arm 2......272
Table 14.3-1.2.1 Duration of exposure to study treatment during post-randomization 
Consolidation phase (ARM 2) - Subset of LSC sub-study Safety Set 
randomized to Arm 2...........................................................................................272
Table 14.3-1.1.3 Duration of exposure to study treatment during re-treatment phase –
Subset of Safety Set entering the re-treatment phase ..........................................273
Table 14.3-1.1.21 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation phase, by stable MR4.0 at 24 months and halving 
time - Safety Set...................................................................................................273
Table 14.3-1.1.22 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation phase, by stable MR4.0 by 24 months and halving 
time - Safety Set...................................................................................................275
Table 14.3-2.1 Relative dose intensity and average daily dose during pre-
randomization Induction/Consolidation phase – Safety Set................................276
Table 14.3-2.1.1 Relative dose intensity and average daily dose during pre-
randomization Induction/Consolidation phase – LSC sub-study Safety Set.......277
Table 14.3-2.2 Relative dose intensity and average daily dose during post-
randomization consolidation phase (ARM 2) – Subset of Safety Set 
randomized to Arm 2...........................................................................................277
Table 14.3-2.2.1 Relative dose intensity and average daily dose during post-
randomization consolidation phase (ARM 2) – Subset of LSC sub-study 
Safety Set randomized to Arm 2..........................................................................277
Table 14.3-2.3 Relative dose intensity and average daily dose during re-treatment 
phase – Subset of Safety Set entering the re-treatment phase .............................278
Table 14.3-3.1 Dose reduction and interruption during pre-randomization 
Induction/Consolidation phase - Safety Set.........................................................279
Table 14.3-3.1.1 Dose reduction and interruption during pre-randomization 
Induction/Consolidation phase – LSC sub-study Safety Set...............................279
Table 14.3-3.2 Dose reduction and interruption during post-randomization 
consolidation phase (ARM 2) – Subset of Safety Set randomized to Arm 2 ......280
Table 14.3-3.2.1 Dose reduction and interruption during post-randomization 
consolidation phase (ARM 2) – Subset of LSC sub-study Safety Set 
randomized to Arm 2...........................................................................................280
Table 14.3-3.3 Dose reduction and interruption during re-treatment phase – Subset of 
Safety Set entering the re-treatment phase ..........................................................281
Table 14.3-4.1 Concomitant medication by ATC class and preferred term during pre-
randomization Induction/Consolidation phase Full Analysis Set........................282
Table 14.3-4.1.1 Concomitant medication by ATC class and preferred term during 
pre-randomization Induction/Consolidation phase LSC sub-study Full 
Analysis Set .........................................................................................................282
Table 14.3-4.2 Concomitant medication by ATC class and preferred term during 
post-randomization consolidation phase (ARM 2)– Subset of Full Analysis 
Set randomized to Arm 2.....................................................................................283


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Table 14.3-4.2.1 Concomitant medication by ATC class and preferred term during 
post-randomization consolidation phase (ARM 2)– Subset of LSC sub-study 
Full Analysis Set randomized to Arm 2 ..............................................................284
Table 14.3-4.3 Concomitant medication by ATC class and preferred term during 
TFR phase – Subset of Full Analysis Set entering the TFR phase......................285
Table 14.3-4.4 Concomitant medication by ATC class and preferred term during re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase..286
Table 14.3-5.1.1 Hematology shift table based on CTCAE grade during Pre-
Randomization pre-randomization Induction/Consolidation –Full Analysis 
Set ........................................................................................................................287
Table 14.3-5.1.2 Hematology shift table based on CTCAE grade during post-
randomization consolidation phase (ARM 2)– Subset of Full Analysis Set 
randomized to Arm 2...........................................................................................289
Table 14.3-5.1.3 Hematology shift table based on CTCAE grade during re-treatment 
phase – Subset of Full Analysis Set entering the re-treatment phase..................290
Table 14.3-5.1.4 Hematology shift table based on CTCAE grade during whole study 
period – Full Analysis Set ...................................................................................292
Table 14.3-5.1.5 Hematology shift table based on CTCAE grade during re-treatment 
phase, SDV sensitivity   – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................293
Table 14.3-5.1.6 Hematology shift table based on CTCAE grade during whole study 
period , SDV sensitivity– Full Analysis Set........................................................293
Table 14.3-5.2.1 Biochemistry shift table based on CTCAE grade during post-
randomization consolidation phase (ARM 2)– Subset of Full Analysis Set 
randomized to Arm 2...........................................................................................294
Table 14.3-5.2.2 Biochemistry shift table based on CTCAE grade during re-
treatment phase– Subset of Full Analysis Set entering the re-treatment phase...294
Table 14.3-5.2.3 Biochemistry shift table based on CTCAE grade during whole 
study period – Full Analysis Set..........................................................................294
Table 14.3-5.2.4 Biochemistry shift table based on CTCAE grade during re-
treatment phase, SDV sensitivity– Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................294
Table 14.3-5.2.5 Biochemistry shift table based on CTCAE grade during whole 
study period, SDV sensitivity – Full Analysis Set ..............................................294
Table 14.3-6.1.1 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during post-randomization consolidation phase 
(ARM 2)– Subset of Full Analysis Set randomized to Arm 2.............................295
Table 14.3-6.1.2 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................296
Table 14.3-6.1.3 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period –Full Analysis Set.........297
Table 14.3-6.1.4 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase...............................298


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Table 14.3-6.1.5 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period, SDV sensitivity –Full 
Analysis Set .........................................................................................................298
Table 14.3-6.2.1 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during post-randomization consolidation phase 
(ARM 2) – Subset of Full Analysis Set randomized to Arm 2............................299
Table 14.3-6.2.2 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................299
Table 14.3-6.2.3 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period –Full Analysis Set.........299
Table 14.3-6.2.4 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase...............................299
Table 14.3-6.2.5 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period, SDV sensitivity –Full 
Analysis Set .........................................................................................................299
Table 14.3-7.1 ECG shift table based on notable values during Pre-randomization 
Induction Consolidation–Full Analysis Set.........................................................300
Table 14.3-7.2 ECG shift table based on notable values during post-randomization
consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................301
Table 14.3-7.3 ECG shift table based on notable values during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase...............................302
Table 14.3-7.4 Notable ECG values during pre-randomization Ind/Cons –Full 
Analysis Set .........................................................................................................303
Table 14.3-7.5 Notable ECG values during post-randomization consolidation phase 
(ARM 2)– Subset of Full Analysis Set randomized to Arm 2.............................304
Table 14.3-7.6 Notable ECG values during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................305
Table 14.3-7.7 ECG shift table based on notable values during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase..305
Table 14.3-7.8 Notable ECG values during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase...............................305
Table 14.3-8.1 Echocardiography assessment at baseline – Full Analysis Set...............306
Table 14.3-8.2 Echocardiography shift table based on overall interpretation - Full 
Analysis Set .........................................................................................................307
Table 14.3-8.3 Echocardiography shift table based on overall interpretation, SDV 
sensitivity - Full Analysis Set..............................................................................308
Table 14.3-9.1 Summary statistics of total cholesterol, HDL, LDL, glucose, 
microalbumin and HbA1c over Induction/Consolidation phase – Full 
Analysis Set .........................................................................................................309
Table 14.3-9.2.1 Total cholesterol shift table based on specific levels during 
Induction Consolidation  – Full Analysis Set......................................................310


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Table 14.3-9.2.2 Total cholesterol shift table based on specific levels during TFR 
phase  – Subset of Full Analysis Set entering the TFR phase .............................311
Table 14.3-9.2.3 Total cholesterol shift table based on specific levels during Re-
treatment phase  – Subset of Full Analysis Set entering the Re-treatment 
phase ....................................................................................................................311
Table 14.3-9.2.4 Total cholesterol shift table based on specific levels during TFR 
phase, SDV sensitivity  – Subset of Full Analysis Set entering the TFR phase..311
Table 14.3-9.2.5 Total cholesterol shift table based on specific levels during Re-
treatment phase, SDV sensitivity  – Subset of Full Analysis Set entering the 
Re-treatment phase ..............................................................................................312
Table 14.3-10.1.1 Fasting glucose shift table based on specific levels during 
Induction Consolidation – Full Analysis Set.......................................................313
Table 14.3-10.1.2 Fasting glucose shift table based on specific levels during TFR 
phase  – Subset of Full Analysis Set entering the TFR phase .............................314
Table 14.3-10.1.3 Fasting glucose shift table based on specific levels during Re-
treatment phase  – Subset of Full Analysis Set entering the Re-treatment 
phase ....................................................................................................................314
Table 14.3-10.1.4 Fasting glucose shift table based on specific levels during TFR 
phase, SDV sensitivity   – Subset of Full Analysis Set entering the TFR phase.314
Table 14.3-10.1.5 Fasting glucose shift table based on specific levels during Re-
treatment phase, SDV sensitivity   – Subset of Full Analysis Set entering the 
Re-treatment phase ..............................................................................................315
Table 14.3-11.1 Vital Signs during Induction Consolidation – Full Analysis Set..........316
Table 14.3-11.2 Vital Signs during TFR phase – Subset of Full Analysis Set entering 
the TFR phase......................................................................................................319
Table 14.3-11.3 Vital Signs during Re-treatment phase  – Subset of Full Analysis Set 
entering the Re-treatment phase ..........................................................................319
Table 14.3-11.4 Vital Signs during TFR phase, SDV sensitivity – Subset of Full 
Analysis Set entering the TFR phase...................................................................320
Table 14.3-11.5 Vital Signs during Re-treatment phase, SDV sensitivity – Subset of 
Full Analysis Set entering the Re-treatment phase..............................................320
Table 14.3-12.1 Survival follow-up – Full Analysis Set.................................................321
Table 14.3-12.2 Survival follow-up, SDV sensitivity  – Full Analysis Set ....................322
Table 14.3-13.1 Safety follow-up – Full analysis Set .....................................................323
Table 14.3-13.2 Safety follow-up, SDV sensitivity  – Full analysis Set.........................323
Section 14.3.1 – Displays of adverse events ...................................................................324
Figure 14.3.1-1.1 Kaplan-Meier analysis of time-to-first CVEs during the pre-
randomization Induction/Consolidation phase – Full Analysis Set.....................324
Figure 14.3.1-1.2 Kaplan-Meier analysis of time-to-first CVEs during the post-
randomization consolidation phase (ARM 2) – Subset of Full Analysis Set 
randomized to Arm 2...........................................................................................325
Figure 14.3.1-1.3 Kaplan-Meier analysis of time-to-first CVEs during the the TFR 
phase – Subset of Full Analysis Set entering the TFR phase ..............................326


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Figure 14.3.1-1.4 Kaplan-Meier analysis of time-to-first CVEs during the re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase..326
Figure 14.3.1-2.1 Number of sorted events by HIS CD34+/CD38+ cells ......................327
Figure 14.3.1-2.2 Number of sorted events by PCR CD34+/CD38+ cells .....................328
Figure 14.3.1-3.1 Number of sorted events by HIS CD34+/CD38- cells .......................328
Figure 14.3.1-3.2 Number of sorted events by PCR CD34+/CD38- cells ......................328
Figure 14.3.1-4.1 Number of sorted events by HIS Immunophenotypically aberrant 
CD34+ cells .........................................................................................................328
Figure 14.3.1-4.2 Number of sorted events by PCR Immunophenotypically aberrant 
CD34+ cells .........................................................................................................328
Figure 14.3.1-5.1 Number of sorted events by HIS Immunophenotypically aberrant 
CD34- cells..........................................................................................................328
Figure 14.3.1-5.2 Number of sorted events by PCR Immunophenotypically aberrant 
CD34- cells..........................................................................................................328
Figure 14.3.1-6.1 Number of HIS+ subjects CD34+/CD38+ cells – LSC substudy 
Full Analysis Set..................................................................................................329
Figure 14.3.1-6.2 Number of PCR subjects CD34+/CD38+ cells – LSC substudy 
Full Analysis Set..................................................................................................330
Figure 14.3.1-7.1 Number of HIS+ subjects CD34+/CD38- cells – LSC substudy 
Full Analysis Set..................................................................................................330
Figure 14.3.1-7.2 Number of PCR subjects CD34+/CD38- cells – LSC substudy Full 
Analysis Set .........................................................................................................330
Figure 14.3.1-8.1 Number of HIS+ subjects Immunophenotypically aberrant CD34+ 
cells – LSC substudy Full Analysis Set...............................................................330
Figure 14.3.1-8.2 Number of PCR subjects Immunophenotypically aberrant CD34+ 
cells – LSC substudy Full Analysis Set...............................................................330
Figure 14.3.1-9.1 Number of HIS+ subjects Immunophenotypically aberrant CD34-
cells – LSC substudy Full Analysis Set...............................................................330
Figure 14.3.1-9.2 Number of PCR subjects Immunophenotypically aberrant CD34-
cells – LSC substudy FAS...................................................................................330
Figure 14.3.1-10 Number of patients with detectable LSC – LSC substudy Full 
Analysis Set .........................................................................................................331
Table 14.3.1-1.1 Overall summary of treatment-emergent adverse events occurring 
during pre-randomization Induction/consolidation phase – Full Analysis Set....332
Table 14.3.1-1.2 Overall summary of treatment-emergent adverse events occurring 
during post-randomization consolidation phase (ARM 2) – Subset of Full 
Analysis Set randomized to Arm 2......................................................................334
Table 14.3.1-1.3 Overall summary of treatment-emergent adverse events occurring 
during re-treatment phase – Subset of Full Analysis Set entering the re-
treatment phase....................................................................................................336
Table 14.3.1-1.4 Overall summary of adverse events occurring during TFR phase –
Subset of Full Analysis Set entering the TFR phase ...........................................337


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Table 14.3.1-2.1 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during pre-randomization Induction/consolidation phase – Full 
Analysis Set .........................................................................................................338
Table 14.3.1-2.2 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during post-randomization consolidation phase (ARM 2) – Subset 
of Full Analysis Set randomized to Arm 2..........................................................338
Table 14.3.1-2.3 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during re-treatment phase – Subset of Full Analysis Set entering 
the re-treatment phase..........................................................................................338
Table 14.3.1-2.4 Overall summary of frequent [1] adverse events occurring during 
TFR phase – Subset of Full Analysis Set entering the TFR phase......................339
Table 14.3.1-3.1.1 Treatment Emergent adverse events incidence, regardless of study 
drug relationship, occurring during pre-randomization 
Induction/consolidation phase by system organ class and preferred term -
overall and maximum grade 3/4 – Full Analysis Set...........................................340
Table 14.3.1-3.1.2 Treatment Emergent adverse events occurence, regardless of 
study drug relationship, occurring during pre-randomization 
Induction/consolidation phase by system organ class and preferred term -
overall and maximum grade 3/4 – Full Analysis Set...........................................341
Table 14.3.1-3.2.1 Treatment Emergent adverse events incidence, regardless of study 
drug relationship, occurring during post-randomization consolidation phase 
(ARM 2) by system organ class and preferred term - overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................342
Table 14.3.1-3.2.2 Treatment Emergent adverse events occurence, regardless of 
study drug relationship, occurring during post-randomization consolidation 
phase (ARM 2) by system organ class and preferred term - overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ..........343
Table 14.3.1-3.3.1 Treatment-emergent adverse events incidence, regardless of study 
drug relationship, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................344
Table 14.3.1-3.3.2 Treatment-emergent adverse events occurrence, regardless of 
study drug relationship, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................345
Table 14.3.1-3.4.1 Adverse events incidence, regardless of study drug relationship, 
by system organ class and preferred term during TFR phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase.......345
Table 14.3.1-3.4.2 Adverse events occurrence, regardless of study drug relationship, 
by system organ class and preferred term during TFR phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase.......345
Table 14.3.1-3.5.1 Frequent [1] Treatment Emergent adverse events incidence, 
regardless of study drug relationship occurring during pre-randomization 
Induction/consolidation phase by system organ class and preferred term -
overall and maximum grade 3/4 – Full Analysis Set...........................................346


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Table 14.3.1-3.5.2 Frequent [1] Treatment Emergent adverse events incidence, 
regardless of study drug relationship occurring during post-randomization 
consolidation phase (ARM 2) by system organ class and preferred term-
overall and maximum grade 3/4  – Subset of Full Analysis Set randomized to 
Arm 2...................................................................................................................346
Table 14.3.1-3.5.3 Frequent [1] Treatment Emergent adverse events incidence, 
regardless of study drug relationship occurring during re-treatment phase by 
system organ class and preferred term- overall and maximum grade 3/4  –
Subset of Full Analysis Set entering the re-treatment phase...............................347
Table 14.3.1-3.5.4 Frequent [1] adverse events incidence, regardless of study drug 
relationship occurring during TFR phase by system organ class and preferred 
term - overall and maximum grade 3/4 – Subset of Full Analysis Set entering 
the TFR phase......................................................................................................347
Table 14.3.1-4.1.1 Serious treatment-emergent adverse events incidence, regardless 
of study drug relationship, by system organ class and preferred term during 
pre-randomization Induction/consolidation phase – overall and maximum 
grade 3/4 –Full Analysis Set................................................................................348
Table 14.3.1-4.1.2 Serious treatment-emergent adverse events occurence, regardless 
of study drug relationship, by system organ class and preferred term during 
pre-randomization Induction/consolidation phase – overall and maximum 
grade 3/4 –Full Analysis Set................................................................................348
Table 14.3.1-4.2.1 Serious treatment-emergent adverse events incidence, regardless 
of study drug relationship, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................349
Table 14.3.1-4.2.2 Serious treatment-emergent adverse events occurrence, regardless 
of study drug relationship, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................349
Table 14.3.1-4.3.1 Serious treatment-emergent adverse events incidence, regardless 
of study drug relationship, by system organ class and preferred term during 
re-treatment phase – overall and maximum grade 3/4 – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................350
Table 14.3.1-4.3.2 Serious treatment-emergent adverse events occurrence, regardless 
of study drug relationship, by system organ class and preferred term during 
re-treatment phase – overall and maximum grade 3/4 – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................350
Table 14.3.1-4.4.1 Serious adverse events incidence, regardless of study drug 
relationship, by system organ class and preferred term during TFR phase –
overall and maximum grade 3/4 – Subset of Full Analysis Set entering the 
TFR phase............................................................................................................350
Table 14.3.1-4.4.2 Serious adverse events occurence, regardless of study drug 
relationship, by system organ class and preferred term during TFR phase –
overall and maximum grade 3/4 – Subset of Full Analysis Set entering the 
TFR phase............................................................................................................350
Table 14.3.1-4.5.1 Frequent [1] Serious Treatment Emergent adverse events 
incidence, regardless of study drug relationship occurring during pre-


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randomization Induction/consolidation phase by system organ class and 
preferred term - overall and maximum grade 3/4 – Full Analysis Set ................351
Table 14.3.1-4.5.2 Frequent [1] Serious Treatment Emergent adverse events 
incidence, regardless of study drug relationship occurring during post-
randomization consolidation phase (ARM 2) by system organ class and 
preferred term - overall and maximum grade 3/4  – Subset of Full Analysis 
Set randomized to Arm 2.....................................................................................351
Table 14.3.1-4.5.3 Frequent [1] Serious Treatment Emergent adverse events 
incidence, regardless of study drug relationship occurring during re-treatment 
phase by system organ class and preferred term - overall and maximum grade 
3/4  – Subset of Full Analysis Set entering the re-treatment phase.....................351
Table 14.3.1-4.5.4 Frequent [1] Serious adverse events incidence, regardless of study 
drug relationship  occurring during TFR phase by system organ class and 
preferred term - overall and maximum grade 3/4  – Subset of Full Analysis 
Set entering the TFR phase..................................................................................351
Table 14.3.1-4.6.1 Serious treatment-emergent adverse events incidence, suspected 
to be study drug related, by system organ class and preferred term during pre-
randomization Induction/consolidation phase  – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................352
Table 14.3.1-4.6.2 Serious treatment-emergent adverse events occurence, suspected 
to be study drug related, by system organ class and preferred term during pre-
randomization Induction/consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................352
Table 14.3.1-4.7.1 Serious treatment-emergent adverse events incidence, suspected 
to be study drug related, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................353
Table 14.3.1-4.7.2 Serious treatment-emergent adverse events occurrence, suspected 
to be study drug related, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ...........................353
Table 14.3.1-4.8.1 Serious treatment-emergent adverse events incidence, suspected 
to be study drug related, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................353
Table 14.3.1-4.8.2 Serious treatment-emergent adverse events occurrence, suspected 
to be study drug related, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................353
Table 14.3.1-4.9.1 Serious adverse events incidence, suspected to be study drug 
related, by system organ class and preferred term during TFR phase – overall 
and maximum grade 3/4 – Subset of Full Analysis Set entering the TFR 
phase ....................................................................................................................353
Table 14.3.1-4.9.2 Serious adverse events occurrence, suspected to be study drug 
related, by system organ class and preferred term during TFR phase – overall 
and maximum grade 3/4 – Subset of Full Analysis Set entering the TFR 
phase ....................................................................................................................354


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Table 14.3.1-5.1.1 Treatment-emergent adverse events incidence leading to study 
drug discontinuation by system organ class and preferred term during pre-
randomization Induction/Consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................354
Table 14.3.1-5.1.2 Treatment-emergent adverse events occurence leading to study 
drug discontinuation by system organ class and preferred term during pre-
randomization Induction/Consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set..........................................................................................355
Table 14.3.1-5.2.1 Treatment-emergent adverse events incidence leading to study 
drug discontinuation by system organ class and preferred term during post-
randomization phase (ARM 2) – overall and maximum grade 3/4 – Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................355
Table 14.3.1-5.2.2 Treatment-emergent adverse events occurrence leading to study 
drug discontinuation by system organ class and preferred term during post-
randomization phase (ARM 2)– overall and maximum grade 3/4 – Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................355
Table 14.3.1-5.3.1 Treatment-emergent adverse events incidence leading to study 
drug discontinuation by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................356
Table 14.3.1-5.3.2 Treatment-emergent adverse events occurrence leading to study 
drug discontinuation by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase......................................................................356
Table 14.3.1-6.1.1 Treatment-emergent adverse events incidence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during pre-randomization Induction/ consolidation phase  – overall and 
maximum grade 3/4 –Full Analysis Set ..............................................................356
Table 14.3.1-6.1.2 Treatment-emergent adverse events occurrence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during pre-randomization Induction/consolidation phase – overall and 
maximum grade 3/4 –Full Analysis Set ..............................................................357
Table 14.3.1-6.2.1 Treatment-emergent adverse events incidence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during post-randomization consolidation phase (ARM 2) – overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ..........357
Table 14.3.1-6.2.2 Treatment-emergent adverse events occurrence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during post-randomization consolidation phase (ARM 2) – overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2 ..........357
Table 14.3.1-6.3.1 Treatment-emergent adverse events incidence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during re-treatment phase – overall and maximum grade 3/4 – Subset of 
Full Analysis Set entering the re-treatment phase...............................................358
Table 14.3.1-6.3.2 Treatment-emergent adverse events occurrence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 


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term during re-treatment phase – overall and maximum grade 3/4 – Subset of 
Full Analysis Set entering the re-treatment phase...............................................358
Table 14.3.1-6.4.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, by specific group and preferred term 
during Pre-randomization Induction/consolidation phase –by treatment arm, 
overall and maximum grade 3/4 – Full Analysis Set...........................................359
Table 14.3.1-6.4.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, by specific group and preferred term 
during Pre-randomization Induction/consolidation phase – by treatment arm, 
overall and maximum grade 3/4 –Full Analysis Set............................................360
Table 14.3.1-6.5.1 Treatment-emergent adverse events of interest incidence by 
specific group and preferred term during post-randomization consolidation 
phase (ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis 
Set randomized to Arm 2.....................................................................................361
Table 14.3.1-6.5.2 Treatment-emergent adverse events of interest occurrence, by  
specific group and preferred term during post-randomization consolidation 
phase (ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis 
Set randomized to Arm 2.....................................................................................362
Table 14.3.1-6.6.1 Treatment-emergent adverse events of interest incidence by 
specific group and preferred term during re-treatment phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment 
phase ....................................................................................................................363
Table 14.3.1-6.6.2 Treatment-emergent adverse events of interest occurrence by 
specific group and preferred term during re-treatment phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment 
phase ....................................................................................................................364
Table 14.3.1-6.7.1 Adverse events of interest incidence by specific group and 
preferred term during TFR phase – overall and maximum grade 3/4 – Subset 
of Full Analysis Set entering the TFR phase.......................................................364
Table 14.3.1-6.7.2 Adverse events of interest occurrence by specific group and 
preferred term during TFR phase – overall and maximum grade 3/4 – Subset 
of Full Analysis Set entering the TFR phase.......................................................364
Table 14.3.1-7.1.1 Treatment Emergent adverse events of interest incidence, 
regardless of study drug relationship, by specific group and preferred term 
and by cardiovascular risk factors during Pre-randomization 
Induction/consolidation phase – by treatment arm, overall and maximum 
grade 3/4 – Full Analysis Set...............................................................................365
Table 14.3.1-7.1.2 Treatment Emergent adverse events of interest occurrence, 
regardless of study drug relationship, by specific group and preferred term 
and by cardiovascular risk factors during Pre-randomization 
Induction/consolidation phase – by treatment arm, overall and maximum 
grade 3/4 –Full Analysis Set................................................................................366
Table 14.3.1-7.2.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 
cardiovascular risk factor– overall and maximum grade 3 or 4 – Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................367


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Table 14.3.1-7.2.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 
cardiovascular risk factor – overall and maximum grade 3 or 4 – Subset of 
Full Analysis Set randomized to Arm 2 ..............................................................368
Table 14.3.1-7.3.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during re-treatment phase, by specific 
group and preferred term, and by cardiovascular risk factor – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................369
Table 14.3.1-7.3.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during re-treatment phase, by specific 
group and preferred term, and by cardiovascular risk factor – Subset of Full 
Analysis Set entering the re-treatment phase.......................................................370
Table 14.3.1-7.4.1 Adverse events of interest incidence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
cardiovascular risk factor – Subset of Full Analysis Set entering the TFR 
phase ....................................................................................................................371
Table 14.3.1-7.4.2 Adverse events of interest occurrence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
cardiovascular risk factor – Subset of Full Analysis Set entering the TFR 
phase ....................................................................................................................371
Table 14.3.1-7.5.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during pre-randomization 
Induction/consolidation phase, by specific group and preferred term and by 4 
cardiovascular risk factors – overall and maximum grade 3/4  –Full Analysis 
Set ........................................................................................................................372
Table 14.3.1-7.5.2 Treatment-emergent adverse events of interest occurence, 
regardless of study drug relationship, during pre-randomization 
Induction/consolidation phase, by specific group and preferred term and by 4 
cardiovascular risk factors – overall and maximum grade 3/4 –Full Analysis 
Set ........................................................................................................................372
Table 14.3.1-7.6.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 4 
categories of cardiovascular risk factors– overall and maximum grade 3 or 4 
– Subset of Full Analysis Set randomized to Arm 2 ...........................................372
Table 14.3.1-7.6.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 4 
categories of cardiovascular risk factors – overall and maximum grade 3 or 4 
– Subset of Full Analysis Set randomized to Arm 2 ...........................................372
Table 14.3.1-7.7.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during re-treatment phase, by specific 
group and preferred term, and by 4 categories of cardiovascular risk factors –
Subset of Full Analysis Set entering the re-treatment phase...............................373
Table 14.3.1-7.7.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during re-treatment phase, by specific 


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group and preferred term, and by 4 categories of cardiovascular risk factors–
Subset of Full Analysis Set entering the re-treatment phase...............................373
Table 14.3.1-7.8.1 Adverse events of interest incidence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
4 categories of cardiovascular risk factors – Subset of Full Analysis Set 
entering the TFR phase........................................................................................374
Table 14.3.1-7.8.2 Adverse events of interest occurrence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
4 categories of cardiovascular risk factors– Subset of Full Analysis Set 
entering the TFR phase........................................................................................374
Table 14.3.1-9.1 On treatment deaths, by system organ class and preferred term 
during pre-randomization Induction/Consolidation phase - Safety Set...............375
Table 14.3.1-9.2 On treatment deaths, by system organ class and preferred term 
during post-randomization consolidation phase (ARM 2) – Subset of Safety 
Set randomized to Arm 2.....................................................................................376
Table 14.3.1-9.3  On treatment deaths, by system organ class and preferred term 
during re-treatment phase – Subset of Safety Set entering the re-treatment 
phase ....................................................................................................................376
Table 14.3.1-10.1.1 Cardiac and vascular adverse events of interest, incidence, by 
treatment arm during the pre-randomization induction/consolidation phase -
Full Analysis Set..................................................................................................377
Table 14.3.1-10.1.2 Cardiac and vascular adverse events of interest, occurence, by 
treatment arm during the pre-randomization induction/consolidation phase -
Full Analysis Set..................................................................................................379
Table 14.3.1-10.2.1 Cardiac and vascular adverse events of interest incidence, during 
the post-randomization consolidation phase (ARM 2) - Subset of Full 
Analysis Set randomized to Arm 2......................................................................380
Table 14.3.1-10.2.2 Cardiac and vascular adverse events of interest occurrence, 
during the post-randomization consolidation phase (ARM 2) - Subset of Full 
Analysis Set randomized to Arm 2......................................................................381
Table 14.3.1-10.3.1 Cardiac and vascular adverse events of interest, incidence, by 
treatment arm during the re-treatment phase – Subset of Full Analysis Set 
entered re-treatment phase...................................................................................381
Table 14.3.1-10.3.2 Cardiac and vascular adverse events of interest, occurence, by 
treatment arm during the re-treatment phase - Subset of Full Analysis Set 
entered re-treatment phase...................................................................................382
Table 14.3.1-10.4.1 Cardiac and vascular adverse events of interest, incidence, by 
treatment arm during the TFR phase – Subset of Full Analysis Set entered 
TFR phase............................................................................................................383
Table 14.3.1-10.4.2 Cardiac and vascular adverse events of interest, occurence, by 
treatment arm during the TFR phase - Subset of Full Analysis Set entered 
TFR phase............................................................................................................383
Table 14.3.1-10.5 Relationship between cardiac and vascular adverse events of 
interest with total cholesterol values - Full Analysis Set.....................................384
Table 14.3.1-10.6 Relationship between cardiac and vascular adverse events of 
interest with glycemic values - Full Analysis Set................................................385


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Table 14.3.1-11.1.1 Kaplan-Meier estimate of time-to-first CVEs during the pre-
randomization induction/consolidation phase – Full analysis set........................386
Table 14.3.1-11.1.2 Kaplan-Meier estimate of time-to-first CVEs during the post-
randomization consolidation phase (ARM 2)– Subset of Full Analysis Set 
patients randomized on Arm 2.............................................................................389
Table 14.3.1-11.2 Kaplan-Meier estimate of time-to-first CVEs during the re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase..390
Table 14.3.1-12.1 Medical history by system organ class and preferred term- Full 
Analysis Set .........................................................................................................391
Table 14.3.1-13.1 Prior exposure to imatinib before screening, MMR, age, and Sokal 
by LSC detection category - LSC sub-study Full Analysis Set...........................392
Table 14.3.1-13.2.1 Percentage from total CD34+ cells, CD34+/CD38+ cells -
Subgroup of LSC sub-study Full Analysis Set, LSC detected ............................393
Table 14.3.1-13.2.2 Percentage from total CD34+ cells, CD34+/CD38- cells -
Subgroup of LSC sub-study Full Analysis Set, LSC detected ............................394
Table 14.3.1-13.2.3 Percentage from total CD34+ cells, Immunophenotypically 
aberrant CD34+ cells - Subgroup of LSC sub-study Full Analysis Set, LSC 
detected................................................................................................................394
Table 14.3.1-13.2.4 Percentage from total CD34+ cells, Immunophenotypically 
aberrant CD34 negative cells - Subgroup of LSC sub-study Full Analysis Set, 
LSC detected........................................................................................................395
Table 14.3.1-13.3.1 Percentage of Ph+ cells, CD34+/CD38- cells - Subgroup of LSC 
sub-study Full Analysis Set, LSC detected..........................................................395
Table 14.3.1-13.3.2 Percentage of Ph+ cells, CD34+/CD38- cells - Subgroup of LSC 
sub-study Full Analysis Set, LSC detected..........................................................395
Table 14.3.1-13.3.3 Percentage of Ph+ cells, Immunophenotypically aberrant CD34+ 
cells - Subgroup of LSC sub-study Full Analysis Set, LSC detected..................395
Table 14.3.1-13.3.4 Percentage of Ph+ cells, Immunophenotypically aberrant CD34 
negative cells - Subgroup of LSC sub-study Full Analysis Set, LSC detected...395
Table 14.3.1-13.4 Total Percentage of CD34+ cells- Subgroup of LSC sub-study Full 
Analysis Set, LSC detected..................................................................................395
Table 14.3.1-13.5 LSC detection - LSC sub-study Full Analysis Set.............................396
Section 14.3.2 – Listings of deaths, other serious and significant adverse events..........397
Listing 14.3.2-1.1 Listing of deaths – Full Analysis Set.................................................397
Listing 14.3.2-1.2 Listing of deaths SDV sensitivity – Full Analysis Set.......................397
Listing 14.3.2-2.1    Listing of adverse events of special interest – Full Analysis Set....398
Listing 14.3.2-2.2   Listing of adverse events leading to study drug discontinuation –
Full Analysis Set..................................................................................................398
Listing 14.3.2-2.3   Listing of adverse events leading to study drug discontinuation 
during re-treatment phase – Subset of Full Analysis Set entering the re-
treatment period...................................................................................................399
Section 14.3.3 – Narratives of deaths, other serious and significant adverse 
events (non statistics and programming deliverables) ........................400
Section 14.3.4 – Abnormal laboratory value listings ......................................................400


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Listing 14.3.4-1.1   Listing of abnormal hematology laboratory value – Full Analysis 
Set ........................................................................................................................400
Listing 14.3.4-2.1   Listing of abnormal biochemistry laboratory value – Full 
Analysis Set .........................................................................................................400
Section 16 – Appendices .................................................................................................401
Section 16.1 – Study information........................................................................401
Section 16.1.6 – Listing of patients receiving test drug(s)/investigational 
product(s) from specific batches where more than one batch was 
used .....................................................................................................401
Section 16.1.7 – Randomization scheme and codes (subject identification and 
treatment assigned)..............................................................................402
Listing 16.1.7-1.1 Randomization schemes - Randomized patients ...............................402
Section 16.1.9 – Documentation of statistical methods.......................................403
Listing 16.1.9.1 Raw Statistical output from Demographic and characteristics at 
baseline– Full Analysis Set..................................................................................404
Listing 16.1.9.1.1 Raw Statistical output from Demographic and characteristics at 
baseline– LSC sub-study Full Analysis Set.........................................................404
Listing 16.1.9.2 Raw Statistical output from History of prior Imatinib therapy – Full 
Analysis Set .........................................................................................................404
Listing 16.1.9.2.1 Raw Statistical output from History of prior Imatinib therapy –
LSC sub-study Full Analysis Set.........................................................................404
Listing 16.1.9.3    Raw Statistical output from Cardiovascular risk factors at baseline 
– Full Analysis Set...............................................................................................405
Listing 16.1.9.4.1   Raw Statistical output from Molecular response MR4.0 at 12 
months of TFR–Subset of Full Analysis Set entering the TFR phase.................405
Listing 16.1.9.4.2   Raw Statistical output from Molecular response MR4.0 at 12 
months of TFR–Subset of Per Protocol Analysis Set entering the TFR phase ...405
Listing 16.1.9.5.1   Raw Statistical output from Kaplan-Meier analysis of treatment-
free survival during the TFR phase – Subset of Full Analysis Set entering the 
TFR phase............................................................................................................406
Listing 16.1.9.5.2   Raw Statistical output from Kaplan-Meier analysis of treatment-
free survival during the TFR phase – Subset of Per Protocol Analysis Set 
entering the TFR phase........................................................................................406
Listing 16.1.9.5.3   Raw Statistical output from Kaplan-Meier analysis of overall 
survival from Randomization–Randomized Set..................................................406
Listing 16.1.9.5.4   Raw Statistical output from Kaplan-Meier analysis of 
progression-free survival during the TFR phase – Subset of Full Analysis Set 
entering the TFR phase........................................................................................406
Listing 16.1.9.6.1   Raw Statistical output from Kaplan-Meier estimate of time-to-
first CVEs during the pre-randomization induction/consolidation phase – Full 
analysis set...........................................................................................................407
Listing 16.1.9.6.2   Raw Statistical output from Kaplan-Meier estimate of time-to-
first CVEs during the post-randomization consolidation phase (ARM 2)–
Subset of Full Analysis Set patients randomized on Arm 2................................407


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Listing 16.1.9.6.3   Raw Statistical output from Kaplan-Meier estimate of time-to-
first CVEs during the re-treatment phase – Subset of Full Analysis Set 
entering the re-treatment phase............................................................................407
Section 16.2 – Patient data listings..................................................................................409
Listing 16.2-1.1 Enrolled patients ...................................................................................409
Section 16.2.1 – Discontinued subjects...........................................................................410
Listing 16.2.1-1.1 Treatment and study completion - Safety Set....................................410
Listing 16.2.1-1.2 Study discontinuation – Full Analysis Set.........................................411
Listing 16.2.1-1.3
Screen failures (All subjects enrolled) ............................................412
Section 16.2.2 – Protocol deviations...............................................................................413
Listing 16.2.2-1.1 Protocol deviations – Enrolled patients .............................................413
Section 16.2.3 – Patients excluded from the efficacy analysis........................................414
Listing 16.2.3-1.1 Analysis set –  All patients ................................................................414
Section 16.2.4 – Demographics and data at screening....................................................415
Listing 16.2.4-1.1 Demographic data – Full Analysis Set ..............................................415
Listing 16.2.4-2.1 Family history – Full Analysis Set ....................................................415
Listing 16.2.4-2.2 Disease history– Full Analysis Set ....................................................416
Listing 16.2.4-3.1 Disease history I– Full Analysis Set..................................................417
Listing 16.2.4-3.2   Disease history II– Full Analysis Set...............................................418
Listing 16.2.4-3.3   Medical history/current medical condition – Full Analysis Set ......418
Listing 16.2.4.4    Cardiovascular risk factors at baseline for patients with not 
evaluable CV risk factor, Full Analysis Set.........................................................419
Section 16.2.5 – Compliance and/or drug concentration data if available (including 
Bioanalytical Data Report) ..................................................................................420
Listing 16.2.5-1.1 Dosage administration records – Full Analysis Set...........................420
Section 16.2.6 – Individual efficacy response data.........................................................420
Listing 16.2.6-1.1 BCR-ABL(IS) ratio and molecular responses during 
Induction/Consolidation and post-randomization consolidation phase (ARM 
2) – Full Analysis Set ..........................................................................................420
Listing 16.2.6-1.2 BCR-ABL(IS) ratio and molecular responses during TFR phase –
Subset of Full Analysis Set entering the TFR phase ...........................................421
Listing 16.2.6-1.3 BCR-ABL(IS) ratio and molecular responses during re-treatment 
phase – Subset of Full Analysis Set entering the re-treatment phase..................421
Listing 16.2.6-2.1 Criteria of successful TFR – Subset of Full Analysis Set entering 
the TFR phase......................................................................................................422
Listing 16.2.6-3.1 Assessment of progression-free survival during the TFR phase –
Subset of Full Analysis Set entering the TFR phase ...........................................423
Listing 16.2.6-3.2 Assessment of treatment-free survival during the TFR phase –
Subset of Full Analysis Set entering the TFR phase ...........................................424
Listing 16.2.6-3.3 Assessment of overall survival From Randomization –
Randomized set....................................................................................................425


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Listing 16.2.6-3.4 Assessment of relapse and treatment status during the TFR phase 
–Subset of Full Analysis Set entering the TFR phase and relapsed ....................426
Listing 16.2.6-4.1    WBC and molecular response in patients with WBC increase 
(CTCAE grade>G1) – Full Analysis Set.............................................................427
Listing 16.2.6-5.1   Individual Efficacy data, Molecular response – Full Analysis Set..428
Listing 16.2.6-5.2   Individual Efficacy data, Bone-marrow I – Full Analysis Set.........429
Listing 16.2.6-5.3   Individual Efficacy data, Bone -marrow II – Full Analysis Set ......430
Listing 16.2.6-6.1.1 Total percentage of CD34+ cells – LSC sub-study Full Analysis 
Set ........................................................................................................................431
Listing 16.2.6-6.2.1 Percentage of cells from total CD34 positive– LSC sub-study 
Full Analysis Set..................................................................................................432
Listing 16.2.6-6.3.1 Number of events sorted– LSC sub-study Full Analysis Set .........433
Listing 16.2.6-6.4.1 Ph+ by HIS– LSC sub-study Full Analysis Set..............................434
Listing 16.2.6-6.5.1 BCR-ABL by RT-PCR– LSC sub-study Full Analysis Set............435
Section 16.2.7 – Adverse event listings...........................................................................436
Listing 16.2.7-1.1 All adverse events – Full Analysis Set ..............................................436
Listing 16.2.7-2.1 Serious adverse events Full Analysis Set ..........................................437
Listing 16.2.7-2.2 Adverse events leading to study drug discontinuation – Full 
Analysis Set .........................................................................................................438
Listing 16.2.7-2.3 Adverse events of interest – Full Analysis Set ..................................439
Listing 16.2.7-3.1 CV risk factors, Nilotinib exposure, glucose and total cholesterol 
rates for patients with cardiac and vascular adverse events of interest, Full 
Analysis Set .........................................................................................................440
Listing 16.2.7-3.2 Cardiac and vascular adverse events of interest, Full Analysis Set...441
Listing 16.2.7-3.3 Outcomes and subsequent concomitant medications for patients 
with cardiac adverse events of interest, Full Analysis Set...................................443
Listing 16.2.7-3.4 Outcomes and subsequent concomitant medications for patients 
with vascular adverse events of interest, Full Analysis Set.................................444
Section 16.2.8 – Laboratory measurements ....................................................................445
Listing 16.2.8-1.1  Hematology laboratory values and normal ranges – Full Analysis 
Set ........................................................................................................................445
Listing 16.2.8-2.1 Biochemistry laboratory values and normal ranges – Full Analysis 
Set ........................................................................................................................446
Listing 16.2.8-3.1 Hematological data and molecular response in patients with 
absolute blasts higher than normal ranges, Full Analysis Set .............................448
Listing 16.2.8-3.2 Hematological data and molecular response in patients with 
absolute metamyelocytes higher than normal ranges, Full Analysis Set.............449
Section 16.2.9 – Vital signs, physical findings and other observations related to 
safety listings .......................................................................................................450
Listing 16.2.9-1.1    Vital signs – Full Analysis Set........................................................450
Listing 16.2.9-2.1    Electrocardiograms – Full Analysis Set..........................................451
Listing 16.2.9-2.2    Echocardiography – Full Analysis Set............................................451


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Listing 16.2.9-3.1    Concomitant medications – Full Analysis Set................................452
Listing 16.2.9- 3.2   Prohibited concomitant medications – Full Analysis Set...............452
Listing 16.2.9-4.1     Prior Imatinib therapy– Full Analysis Set .....................................453
Listing 16.2.9-4.2     Prior antineoplastic therapy, other than Imatinib – Full Analysis 
Set ........................................................................................................................453
Listing 16.2.9-5.1    Survival follow-up– Full Analysis set ............................................454
Listing 16.2.9-5.2    Safety follow-up– Full Analysis set................................................455
Listing 16.2.9-6    Prior imatinib exposure – LSC sub-study Full Analysis Set .............456


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3. Shells and specification for CSR
3.1
Shells and specifications for sections 10 of the CSR (In-textText 
tables, listings and figures)
Document History – Changes compared to previous version of RAP module 7.1
1.
General guidance
1.1
Document headers
1.2
Rules of presentation
1.3
Document headers
1.4
Presentation of table numbering and titles within this document
1.5
Treatment group labels and ordering
1.6
Distribution logistics
2.
Overall table of contents for statistics and programming output
Tables, Listing Figures
3.
Shells and specification for CSR
3.1
Shells and specifications for sections 10 of the CSR (In-textText tables, 
listings and figures)
Section 10
Table 10-1 Analysis sets – All patients
Table 10-2 Patient disposition during Induction/Consolidation phase and post-
Randomization Consolidation phase -Enrolled patients
Table 10-3 Demographic and characteristics at baseline – Full Analysis Set
Table 10-4 Disease history – Full Analysis Set
Table 10-5 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation Safety Set
Table 10-6 Duration of exposure to study treatment during post-randomization 
Consolidation phase (ARM 2) - Subset of Safety Set randomized to Arm 2
Table 11-1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set
Table 11-2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
Arm 2
Table 11-3 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set
Table 11-4 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
Arm 2
Table 11-5 Primary endpoint, Molecular response MR4.0 at 12 months of TFR 
phase–Subset of Full Analysis Set entering the TFR phase
Table 11-6 Secondary endpoint Kaplan-Meier analysis of treatment-free survival 
during the TFR phase – Subset of Full Analysis Set entering the TFR phase


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Table 11-7 Secondary endpoint, Molecular response 4.0 during post-randomization 
consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
Arm 2
Table 11-8 Secondary endpoint, Kaplan-Meier analysis of overall survival from 
Randomization–Randomized Set
Table 12-1 Overall summary of treatment-emergent adverse events occurring during 
pre-randomization Induction/consolidation phase – Full Analysis Set
Table 12-2 Overall summary of treatment-emergent adverse events occurring during 
post-randomization consolidation phase (ARM 2) – Subset of Full Analysis 
Set randomized to Arm 2
Table 12-3 Overall summary of treatment-emergent adverse events occurring during 
re-treatment phase – Subset of Full Analysis Set entering the re-treatment 
phase
Table 12-4 Overall summary of adverse events occurring during TFR phase – Subset 
of Full Analysis Set entering the TFR phase
Table 12-5
Overall summary of frequent [1] treatment-emergent adverse 
events occurring during pre-randomization Induction/consolidation phase –
Full Analysis Set
Table 12-6 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during post-randomization Consolidation phase (ARM 2) – Subset 
of Full Analysis Set randomized to Arm 2
Table 12-7 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during re-treatment phase – Subset of Full Analysis Set entering 
the re-treatment phase
Table 12-8 Overall summary of frequent [1] adverse events occurring during TFR 
phase – Subset of Full Analysis Set entering the TFR phase
Table 12-9 Serious treatment-emergent adverse events incidence, regardless of study 
drug relationship, by system organ class and preferred term during pre-
randomization Induction/consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set
Table 12-10 Serious treatment-emergent adverse events incidence, regardless of 
study drug relationship, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
Table 12-11 Serious treatment-emergent adverse events incidence, regardless of 
study drug relationship, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase
Table 12-12 Serious adverse events incidence, regardless of study drug relationship, 
by system organ class and preferred term during TFR phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase
Table 12-13 Treatment-emergent adverse events of interest incidence, regardless of 
study drug relationship, by specific group and preferred term during Pre-
randomization Induction/consolidation phase –by treatment arm, overall and 
maximum grade 3/4 – Full Analysis Set


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Table 12-14 Treatment-emergent adverse events of interest incidence by specific 
group and preferred term during post-randomization Consolidation phase 
(ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis Set 
randomized to Arm 2
Table 12-15 Treatment-emergent adverse events of interest incidence by specific 
group and preferred term during re-treatment phase – overall and maximum 
grade 3/4 – Subset of Full Analysis Set entering the re-treatment phase
Table 12-16 Adverse events of interest incidence by specific group and preferred 
term during TFR phase – overall and maximum grade 3/4 – Subset of Full 
Analysis Set entering the TFR phase
Table 12-17 Treatment-emergent adverse events incidence leading to study drug 
discontinuation by system organ class and preferred term during pre-
randomization Induction/Consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set
Table 12-18 Treatment-emergent adverse events incidence leading to study drug 
discontinuation by system organ class and preferred term during post-
randomizationphase (ARM 2) – overall and maximum grade 3/4 – Subset of 
Full Analysis Set randomized to Arm 2
Table 12-19 On treatment deaths, by system organ class and preferred term during 
pre-randomization Induction/Consolidation phase - Safety Set
Table 12-20 On treatment deaths, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – Subset of Safety Set 
randomized to Arm 2
Table 12-21 On treatment deaths, by system organ class and preferred term during 
re-treatment phase – Subset of Safety Set entering the re-treatment phase
Listing 12-1 Listing of deaths – Full Analysis Set
Figure 11-1 Primary endpoint, Bar plot MR4.0 at 12 months of TFR phase –Subset 
of Full Analysis Set entering the TFR phase
Figure 11-2 Kaplan-Meier analysis of treatment-free survival during the TFR phase 
–Subset of Full Analysis Set entering the TFR phase
3.2
Shells and specifications for Sections 14 and 16 of the CSR
Section 14 – tables, figures and graphs referred to but not included in the text
Section 14.1 – Demographic data
Table 14.1-1.1 Enrollment by country and center – All patients
Table 14.1-1.2 Randomization by country and center – Randomized patients
Table 14.1-1.3
Patient disposition (Screening failures), All patients
Table 14.1-2.1 Patient disposition during Induction/Consolidation phase and post-
Randomization Consolidation phase -Enrolled patients
Table 14.1-2.2 Patient disposition in each randomized arm – Full Analysis Set
Table 14.1-2.2.1 Patient disposition – Enrolled patients in LSC substudy
Table 14.1-2.3 Analysis sets –All patients
Table 14.1-2.4 Not Randomized patients - Enrolled patients
Table 14.1-2.5   Patient disposition, Overall and by year-phase -Enrolled patients


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Table 14.1-2.6 Patients discontinued and reason for discontinuation – Full Analysis 
Set
Table 14.1-2.6.1 Patients discontinued and reason for discontinuation, SDV 
sensitivity – Full Analysis Set
Table 14.1-2.7 Summary of TFR phase – Full Analysis Set
Table 14.1-2.7.1 Summary of TFR phase, SDV sensitivity – Full Analysis Set
Table 14.1-2.8    Summary of re-treatment phase – Full Analysis Set
Table 14.1-2.8.1 Summary of re-treatment phase, SDV sensitivity – Full Analysis 
Set
Table 14.1-2.9 Summary of patients with relapse during the TFR phase but no 
entering re-treatment phase –-Subset of Full Analysis Set entering the TFR 
phase
Table 14.1-3.1 Demographic and characteristics at baseline– Full Analysis Set
Table 14.1-3.1.1 Demographic and characteristics at baseline– LSC sub-study Full 
Analysis Set
Table 14.1-4.1 Disease history – Full Analysis Set
Table 14.1-4.1.1 Disease history – LSC sub-study Full Analysis Set
Table 14.1-5.1 History of prior Imatinib therapy – Full Analysis Set
Table 14.1-5.1.1 History of prior Imatinib therapy – LSC sub-study Full Analysis Set
Table 14.1-5.2 Prior antineoplastic therapy, other than Imatinib, by ATC class and 
preferred term -  Full Analysis Set
Table 14.1-6.1 Cardiovascular risk factors at baseline – Full Analysis Set
Table 14.1-6.2 Cardiovascular risk factors (based on medical history, laboratory 
values and vital signs at baseline) – Full Analysis Set
Section 14.2 – Efficacy and other non-safety data (e.g. PK, PK/PD, Health Econ.,
QoL)
Figure 14.2-1.1 Box-plot of BCR-ABL ratio (IS) during pre-randomization 
Induction/Consolidation phase – Full Analysis Set
Figure 14.2-1.2 Box-plot of BCR-ABL ratio (IS) during post-randomization 
Consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
ARM 2
Figure 14.2-1.3 Box-plot of BCR-ABL ratio (IS) during TFR phase – Subset of Full 
Analysis Set entered TFR
Figure 14.2-1.4 Box-plot of BCR-ABL ratio (IS) during re-treatment phase – Subset 
of Full Analysis Set entered re-treatment
Figure 14.2-1.5 Box-plot of BCR-ABL ratio (IS) during TFR phase – , SDV 
sensitivity Subset of Full Analysis Set entered TFR
Figure 14.2-1.6 Box-plot of BCR-ABL ratio (IS) during re-treatment phase, SDV 
sensitivity –Subset of Full Analysis Set entered re-treatment
Figure 14.2-2.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase - Full Analysis Set


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Figure 14.2-2.1.2 Raw cumulative incidence of MMR during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
ARM 2
Figure 14.2-2.2.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio - Full 
Analysis Set
Figure 14.2-2.2.2 Raw cumulative incidence of MMR during post-randomization 
Consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to ARM 2
Figure 14.2-2.3.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set
Figure 14.2-2.3.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
ARM 2
Figure 14.2-2.3.11 Raw cumulative incidence of MR 4.0, Randomized vs Not 
Randomized, during pre-randomization Induction/Consolidation phase - Full 
Analysis Set
Figure 14.2-2.4.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio - Full 
Analysis Set
Figure 14.2-2.4.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to ARM 2
Figure 14.2-2.5.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set
Figure 14.2-2.5.11 Raw cumulative incidence of MR 4.5, Randomized vs Not 
Randomized, during pre-randomization Induction/Consolidation phase- Full 
Analysis Set
Figure 14.2-2.5.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
ARM 2
Figure 14.2-2.6.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio - Full 
Analysis Set
Figure 14.2-2.6.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to ARM 2
Figure 14.2-2.7.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline
Figure 14.2-2.8.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching MR 
4.0 at baseline
Figure 14.2-2.9.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching MR 
4.5 at baseline


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Figure 14.2-2.9.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Induction/Consolidation phase (ARM 2)- Subset of Full Analysis Set patients 
not reaching MR 4.5 at baseline, randomized to ARM 2.
Figure 14.2-2.10.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set
Figure 14.2-2.10.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) by BCR-ABL(IS) ratio at baseline - Subset of
Full Analysis Set randomized to ARM 2.
Figure 14.2-2.11.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set
Figure 14.2-2.11.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) by BCR-ABL(IS) ratio at baseline - Subset of 
Full Analysis Set randomized to ARM 2.
Figure 14.2-2.12.1 Box-plot of BCR-ABL ratio (IS) during pre-randomization 
Induction/Consolidation phase, excluding outliers (BCR-ABL (IS) ratio>10 -
Full Analysis Set
Figure 14.2-2.12.2 Box-plot of BCR-ABL ratio (IS) over post-randomization 
Consolidation phase (ARM 2), excluding outliers (BCR-ABL (IS) ratio>10 -
Subset of Full Analysis Set randomized to ARM 2.
Figure 14.2-13.1 Raw cumulative incidence of loss of MMR during TFR – Subset of 
Full Analysis Set entering the TFR phase
Figure 14.2-13.2 Raw cumulative incidence of MMR during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase
Figure 14.2-13.3 Raw cumulative incidence of loss of MMR during TFR, SDV 
sensitivity – Subset of Full Analysis Set entering the TFR phase
Figure 14.2-13.4 Raw cumulative incidence of MMR during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase
Figure 14.2-14.1 Raw cumulative incidence of loss of MR4.0 during TFR phase –
Subset of Full Analysis Set entering the TFR phase
Figure 14.2-14.2 Raw cumulative incidence of MR4.0 during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase
Figure 14.2-14.3 Raw cumulative incidence of loss of MR4.0 during TFR phase, 
SDV sensitivity –Subset of Full Analysis Set entering the TFR phase
Figure 14.2-14.4 Raw cumulative incidence of MR4.0 during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase
Figure 14.2-15.1 Raw cumulative incidence of loss of MR4.5 during TFR phase –
Subset of Full Analysis Set entering the TFR phase with MR4.5
Figure 14.2-15.2 Raw cumulative incidence of MR4.5 during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase
Figure 14.2-15.3 Raw cumulative incidence of loss of MR4.5 during TFR phase, 
SDV sensitivity – Subset of Full Analysis Set entering the TFR phase with 
MR4.5


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Figure 14.2-15.4 Raw cumulative incidence of MR4.5 during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase
Figure 14.2-16 Bar plot MR4.0 at 12 months of TFR phase –Subset of Full Analysis 
Set entering the TFR phase
Figure 14.2-16.2 Bar plot MR4.0 at month 12 TFR phase , SDV sensitivity –Subset 
of Full Analysis Set entering the TFR phase
Figure 14.2-17.1 Kaplan-Meier analysis of progression-free survival during the TFR 
phase –Subset of Full Analysis Set entering the TFR phase
Figure 14.2-17.2 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase –Subset of Full Analysis Set entering the TFR phase
Figure 14.2-17.3 Kaplan-Meier analysis of progression-free survival during the TFR 
phase, SDV sensitivity –Subset of Full Analysis Set entering the TFR phase
Figure 14.2-17.4 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase, SDV sensitivity –Subset of Full Analysis Set entering the TFR phase
Figure 14.2-18.1 Kaplan-Meier analysis of reachievement of MMR, after loss of 
response in TFR –Subset of Full Analysis Set entering the re-treatment phase
Figure 14.2-18.2 Kaplan-Meier analysis of reachievement of MR4.0, after loss of 
response in TFR – Subset of Full Analysis Set entering the re-treatment phase
Figure 14.2-18.3 Kaplan-Meier analysis of reachievement of MMR, after loss of 
response in TFR, SDV sensitivity –Subset of Full Analysis Set entering the 
re-treatment phase
Figure 14.2-18.4 Kaplan-Meier analysis of reachievement of MR4.0, after loss of 
response in TFR, SDV sensitivity – Subset of Full Analysis Set entering the 
re-treatment phase
Table 14.2-1.1 Description of BCR-ABL (IS) ratio at Month 3 and halving time of 
BCR-ABL (IS) ratio subgroups – Full Analysis Set
Table 14.2-2.1.1 Molecular response MR4.0 at 12 months of TFR–Subset of Full 
Analysis Set entering the TFR phase
Table 14.2-2.1.2 Molecular response MR4.0 at 12 months of TFR–Subset of Per 
Protocol Analysis Set entering the TFR phase
Table 14.2-2.1.3 Molecular response MR4.0 at 12 months of TFR–Full Analysis Set
Table 14.2-2.1.4 Molecular response MR4.0 at 12 months of TFR–Per Protocol 
Analysis Set
Table 14.2-2.1.5 Molecular response MR4.0 at 12 months of TFR– Subset of Full 
Analysis Set entering the TFR phase with MR4.0 achieved up to month 3 of 
pre-randomization Induction/Consolidation phase
Table 14.2-2.1.6 Molecular response MR4.0 at 12 months of TFR– Subset of Full 
Analysis Set entering the TFR phase with MR4.5 achieved up to month 3 of 
pre-randomization Induction/Consolidation phase
Table 14.2-2.1.7 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –
Subset of Full Analysis Set entering the TFR phase
Table 14.2-2.1.8 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –
Subset of Per Protocol Analysis Set entering the TFR phase


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Table 14.2-2.1.9 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –
Full Analysis Set
Table 14.2-2.1.10 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity 
–Per Protocol Analysis Set
Table 14.2-2.2.1 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase – Subset of Full Analysis Set entering the TFR phase
Table 14.2-2.2.2 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase – Subset of Per Protocol Analysis Set entering the TFR phase
Table 14.2-2.2.3 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase, SDV sensitivity – Subset of Full Analysis Set entering the TFR phase
Table 14.2-2.2.4 Kaplan-Meier analysis of treatment-free survival during the TFR 
phase, SDV sensitivity – Subset of Per Protocol Analysis Set entering the 
TFR phase
Table 14.2-2.3 Kaplan-Meier analysis of overall survival from Randomization–
Randomized Set
Table 14.2-2.4 Kaplan-Meier analysis of progression-free survival during the TFR 
phase –- Subset of Full Analysis Set entering the TFR phase
Table 14.2-2.5 Kaplan-Meier analysis of overall survival from Randomization, SDV 
sensitivity –Randomized Set
Table 14.2-2.6 Kaplan-Meier analysis of progression-free survival during the TFR 
phase, SDV sensitivity –- Subset of Full Analysis Set entering the TFR phase
Table 14.2-3.1 Major molecular response during pre-randomization 
Induction/Consolidation phase –Full Analysis Set
Table 14.2-3.1.1 Major molecular response during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set
Table 14.2-3.2 Major molecular response during post-randomization consolidation 
phase (ARM 2)– Subset of Full Analysis Set randomized to Arm 2
Table 14.2-3.2.1 Major molecular response during post-randomization consolidation 
phase (ARM 2) – LSC sub-study Full Analysis Set randomized to Arm 2
Table 14.2-3.3 Major molecular response during TFR phase –Subset of Full Analysis 
Set patients entered TFR phase
Table 14.2-3.4 Major molecular response during re-treatment phase–Subset of Full 
Analysis Set patients entered re- treatment phase
Table 14.2-3.5 Major molecular response during TFR phase –Subset of Full Analysis 
Set patients entered TFR phase with MR4.0 achieved up to month 3 of pre-
randomization Induction/Consolidation phase
Table 14.2-3.6 Major molecular response during TFR phase –Subset of Full Analysis 
Set patients entered TFR phase with MR4.5 achieved up to month 3 of pre-
randomization Induction/Consolidation phase
Table 14.2-3.7 Major molecular response during TFR phase, SDV sensitivity –
Subset of Full Analysis Set patients entered TFR phase
Table 14.2-3.8 Major molecular response during re-treatment phase, SDV sensitivity 
–Subset of Full Analysis Set patients entered re- treatment phase


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Table 14.2-4.1 Molecular response 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set
Table 14.2-4.1.1 Molecular response 4.0 during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set
Table 14.2-4.2.1 Molecular response 4.0 during post-randomization consolidation 
phase (ARM 2) – Subset of Full Analysis Set randomized to Arm 2
Table 14.2-4.2.2 Molecular response 4.0 during post-randomization consolidation 
phase (ARM 2) – Subset of  Per Protocol randomized to Arm 2
Table 14.2-4.2.11 Molecular response 4.0 during post-randomization consolidation 
phase (ARM 2) – Subset of  LSC sub-study Full Analysis Set randomized to 
Arm 2
Table 14.2-4.3.1 Molecular response 4.0 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase
Table 14.2-4.3.2 Molecular response 4.0 during TFR phase – Subset of Per Protocol 
Analysis Set entering the TFR phase
Table 14.2-4.3.3 Molecular response 4.0 during TFR phase , SDV sensitivity –
Subset of Full Analysis Set entering the TFR phase
Table 14.2-4.4 Molecular response 4.0 during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase
Table 14.2-4.5 Molecular response 4.0 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.0 achieved up to month 3 of pre-
randomization Induction/Consolidation phase
Table 14.2-4.6 Molecular response 4.0 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.5 achieved up to month 3 of pre-
randomization Induction/Consolidation phase
Table 14.2-4.7 Molecular response 4.0 during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase
Table 14.2-5.1 Molecular response 4.5 during pre-randomization 
Induction/Consolidation– Full Analysis Set
Table 14.2-5.1.1 Molecular response 4.5 during pre-randomization 
Induction/Consolidation– LSC sub-study Full Analysis Set
Table 14.2-5.2 Molecular response 4.5 during post-randomization consolidation 
phase (ARM 2) – Subset of Full Analysis Set randomized to Arm 2
Table 14.2-5.2.1 Molecular response 4.5 during post-randomization consolidation 
phase (ARM 2) – Subset of LSC sub-study Full Analysis Set randomized to  
Arm 2
Table 14.2-5.3 Molecular response 4.5 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase
Table 14.2-5.4 Molecular response 4.5 during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase
Table 14.2-5.5 Molecular response 4.5 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.0 achieved up to month 3 of pre-
randomization Induction/Consolidation phase


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Table 14.2-5.6 Molecular response 4.5 during TFR phase – Subset of Full Analysis 
Set entering the TFR phase with MR4.5 achieved up to month 3 of pre-
randomization Induction/Consolidation phase
Table 14.2-5.7 Molecular response 4.5 during TFR phase, SDV sensitivity – Subset 
of Full Analysis Set entering the TFR phase
Table 14.2-5.8 Molecular response 4.5 during re-treatment phase, SDV sensitivity  –
Subset of Full Analysis Set entering the re-treatment phase
Table 14.2-6.1 Raw cumulative incidence MMR during pre-randomization 
Induction/Consolidation phase – Full Analysis Set
Table 14.2-6.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set
Table 14.2-6.2 Raw cumulative incidence MMR during post-randomization 
Consolidation phase (ARM 2)  - Subset of  Full Analysis Set patients 
randomized to ARM 2
Table 14.2-6.2.1 Raw cumulative incidence MMR during post-randomization 
Consolidation phase (ARM 2)  - Subset of  LSC sub-study Fulls Anslysis Set 
randomized to ARM 2
Table 14.2-6.3 Raw cumulative incidence of MMR during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase
Table 14.2-6.4 Raw cumulative incidence of MMR during re-treatment phase , SDV 
sensitivity  – Subset of Full Analysis Set entering the re-treatment phase
Table 14.2-7.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set
Table 14.2-7.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set
Table 14.2-7.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
ARM 2
Table 14.2-7.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) – Subset of LSC sub-study Full Analysis Set  
randomized to ARM 2
Table 14.2-7.3 Raw cumulative incidence of MR 4.0 during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase
Table 14.2-7.4 Raw cumulative incidence of MR 4.0 during re-treatment phase, SDV 
sensitivity  – Subset of Full Analysis Set entering the re-treatment phase
Table 14.2-8.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set
Table 14.2-8.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set
Table 14.2-8.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to 
Arm 2
Table 14.2-8.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) - Subset of LSC sub-study Full Analysis Set 
randomized to Arm 2


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Table 14.2-8.3 Raw cumulative incidence of MR 4.5 during re-treatment phase -
Subset of Full Analysis Set entering the re-treatment phase
Table 14.2-8.4 Raw cumulative incidence of MR 4.5 during re-treatment phase , 
SDV sensitivity - Subset of Full Analysis Set entering the re-treatment phase
Table 14.2-9.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – Full 
Analysis Set
Table 14.2-9.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – LSC 
sub-study Full Analysis Set
Table 14.2-9.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to Arm 2
Table 14.2-9.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of LSC sub-study Full Analysis Set randomized to Arm 2
Table 14.2-9.3 Raw cumulative incidence of MMR during re-treatment phase by 
halving time of BCR-ABL (IS) ratio – Subset of Full Analysis Set entering 
the re-treatment phase
Table 14.2-10.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – Full 
Analysis Set
Table 14.2-.10.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – LSC 
sub-study Full Analysis Set
Table 14.2-10.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to Arm 2
Table 14.2-10.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of LSC sub-study Full Analysis Set randomized to Arm 2
Table 14.2-10.3 Raw cumulative incidence of MR4.0 during re-treatment phase by 
halving time of BCR-ABL (IS) ratio – Subset of Full Analysis Set entering 
the re-treatment phase
Table 14.2-11.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – Full 
Analysis Set
Table 14.2-.11.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio – LSC 
sub-study Full Analysis Set
Table 14.2-11.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of Full Analysis Set randomized to Arm 2
Table14.2-11.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subset of LSC sub-study Full Analysis Set randomized to Arm 2


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Table 14.2-11.3 Raw cumulative incidence of MR4.5 during re-treatment phase by 
halving time of BCR-ABL (IS) ratio – Subset of Full Analysis Set entering 
the re-treatment phase
Table 14.2-12.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – Full 
Analysis Set
Table 14.2-12.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – LSC 
sub-study Full Analysis Set
Table 14.2-12.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
Full Analysis Set randomized to Arm 2
Table 14.2-12.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
LSC sub-study Full Analysis Set randomized to Arm 2
Table 14.2-12.3 Raw cumulative incidence of MMR during re-treatment phase by 
BCR-ABL (IS) ratio at Month 3 – Subset of Full Analysis Set entering the re-
treatment phase
Table 14.2-13.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – Full 
Analysis Set
Table 14.2-13.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – LSC 
sub-study Full Analysis Set
Table 14.2-13.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
Full Analysis Set randomized to Arm 2
Table 14.2-13.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
LSC sub-study Full Analysis Set randomized to Arm 2
Table 14.2-13.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by 
BCR-ABL (IS) ratio at Month 3 – Subset of Full Analysis Set entering the re-
treatment phase
Table 14.2-14.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – Full 
Analysis Set
Table 14.2-14.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at Month 3 – LSC 
sub-study Full Analysis Set
Table 14.2-14.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
Full Analysis Set randomized to Arm 2
Table 14.2-14.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-ABL (IS) ratio at Month 3 - Subset of 
LSC sub-study Full Analysis Set randomized to Arm 2


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Table 14.2-14.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by 
BCR-ABL (IS) ratio at Month 3 – Subset of Full Analysis Set entering the re-
treatment phase
Table 14.2-15.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by Sokal Risk category– Full Analysis Set
Table 14.2-15.2 Raw cumulative incidence of MR4.0 during pre-randomization 
Induction/Consolidation phase by Sokal Risk category– Full Analysis Set
Table 14.2-15.3 Raw cumulative incidence of MR4.5 during pre-randomization 
Induction/Consolidation phase by Sokal Risk category– Full Analysis Set
Table 14.2-16.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by time since initial diagnosis of CML– Full 
Analysis Set
Table 14.2-16.2 Raw cumulative incidence of MR4.0 during pre-randomization 
Induction/Consolidation phase by time since initial diagnosis of CML – Full 
Analysis Set
Table 14.2-16.3 Raw cumulative incidence of MR4.5 during pre-randomization 
Induction/Consolidation phase by time since initial diagnosis of CML – Full 
Analysis Set
Table 14.2-17.1 Suboptimal response up to 24 months of pre-randomization 
Induction/Consolidation phase -  Full Analysis Set patients who prematurely 
discontinued the pre-randomization Induction/Consolidation phase
Table 14.2-17.2 Suboptimal response up to 12 months of post-randomization 
Consolidation phase (ARM 2)  - Subset of  Full Analysis Set patients who 
prematurely discontinued the Induction/Consolidation phase randomized to 
Arm 2
Table 14.2-18.1 Suboptimal response up to 24 months of pre-randomization 
Induction/Consolidation phase - Full Analysis Set
Table 14.2-18.2 Suboptimal response up to 12 months of post-randomization 
Consolidation phase - Subset of Full Analysis Set, randomized to ARM 2
Table 14.2-19.1 Kinetics of BCR-ABL (IS) ratio during pre-randomization 
Induction/Consolidation phase – Full Analysis Set
Table 14.2-19.1.1 Kinetics of BCR-ABL (IS) ratio during pre-randomization 
Induction/Consolidation phase – LSC sub-study Full Analysis Set
Table 14.2-19.2 Kinetics of BCR-ABL (IS) ratio during post-randomization 
consolidation phase (ARM 2) –Subset of Full Analysis Set randomized to
Arm 2
Table 14.2-19.2.1 Kinetics of BCR-ABL (IS) ratio during post-randomization 
consolidation phase (ARM 2) –Subset of LSC sub-study Full Analysis Set 
randomized to Arm 2
Table 14.2-19.3 Kinetics of BCR-ABL (IS) ratio during TFR phase – Subset of Full 
Analysis Set entering the TFR phase
Table 14.2-19.4 Kinetics of BCR-ABL (IS) ratio during re-treatment phase – Subset 
of Full Analysis Set entering the re-treatment phase
Table 14.2-19.5 Kinetics of BCR-ABL (IS) ratio during TFR phase, SDV sensitivity   
– Subset of Full Analysis Set entering the TFR phase


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Table 14.2-19.6 Kinetics of BCR-ABL (IS) ratio during re-treatment phase , SDV 
sensitivity  – Subset of Full Analysis Set entering the re-treatment phase
Table 14.2-20.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline
Table 14.2-20.2 Raw cumulative incidence of MMR during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MMR at baseline, randomized to ARM 2
Table 14.2-21.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching MR 
4.0 at baseline
Table 14.2-21.2 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MR 4.0 at baseline, randomized to ARM 2
Table 14.2-22.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase -  Full Analysis Set patients not reaching MR 
4.5 at baseline
Table 14.2-22.2 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2)  - Subset of  Full Analysis Set patients not 
reaching MR 4.5 at baseline, randomized to ARM 2
Table 14.2-22.3 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline
Table 14.2-22.4 Raw cumulative incidence of MR 4.0 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MMR at baseline, randomized to ARM 2
Table 14.2-22.5 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase - Full Analysis Set patients not reaching 
MMR at baseline
Table 14.2-22.6 Raw cumulative incidence of MR 4.5 during post-randomization 
Consolidation phase (ARM 2) - Subset of Full Analysis Set patients not 
reaching MMR at baseline, randomized to ARM 2
Table 14.2-23.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline -  Full 
Analysis Set
Table 14.2-23.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at baseline– LSC sub-
study Full Analysis Set
Table 14.2-23.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
Full Analysis Set, randomized to ARM 2
Table 14.2-23.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2


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Table 14.2-23.3 Raw cumulative incidence of MMR during re-treatment phase by 
BCR-BL(IS) ratio at baseline – Subset of Full Analysis Set entering the re-
treatment phase
Table 14.2-24.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set
Table 14.2-24.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at baseline– LSC sub-
study Full Analysis Set
Table 14.2-24.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
Full Analysis Set, randomized to ARM 2
Table 14.2-24.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2
Table 14.2-24.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by 
BCR-BL(IS) ratio at baseline – Subset of Full Analysis Set entering the re-
treatment phase
Table 14.2-25.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL(IS) ratio at baseline - Full 
Analysis Set
Table 14.2-25.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by BCR-ABL (IS) ratio at baseline– LSC sub-
study Full Analysis Set
Table 14.2-25.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
Full Analysis Set, randomized to ARM 2
Table 14.2-25.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by BCR-BL(IS) ratio at baseline - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2
Table 14.2-25.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by 
BCR-BL(IS) ratio at baseline – Subset of Full Analysis Set entering the re-
treatment phase
Table 14.2-26.1 Raw cumulative loss of MMR during TFR phase –Subset of Full 
Analysis Set entering the TFR phase
Table 14.2-26.2 Raw cumulative loss of MR4.0 during TFR phase –Subset of Full 
Analysis Set entering the TFR phase
Table 14.2-26.3 Raw cumulative loss of MR4.5 during TFR phase –Subset of Full 
Analysis Set entering the TFR phase with MR4.5
Table 14.2-26.4 Raw cumulative loss of MMR during TFR phase, SDV sensitivity  –
Subset of Full Analysis Set entering the TFR phase
Table 14.2-26.5 Raw cumulative loss of MR4.0 during TFR phase, SDV sensitivity 
–Subset of Full Analysis Set entering the TFR phase
Table 14.2-26.6 Raw cumulative loss of MR4.5 during TFR phase, SDV sensitivity 
–Subset of Full Analysis Set entering the TFR phase with MR4.5


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Table 14.2-27.1 Descriptive Statistics for CD34 cells: Total percentage – LSC sub-
study Full Analysis Set
Table 14.2-28.1 Descriptive Statistics for CD34+/CD38+ cells: Percentage from 
total CD34+ cells – LSC sub-study Full Analysis Set
Table 14.2-28.2 Descriptive Statistics for number of events sorted in CD34+/CD38+ 
cells – LSC sub-study Full Analysis Set
Table 14.2-28.3 Ph+ by HIS status, in CD34+/CD38+ cells – LSC sub-study Full 
Analysis Set
Table 14.2-28.4 Descriptive statistics of Ph+ in CD34+/CD38+ cells– LSC sub-study 
Full Analysis Set
Table 14.2-28.5 BCR-ABL by RT-PCR status, in CD34+/CD38+ cells – LSC sub-
study Full Analysis Set
Table 14.2-29.1 Descriptive Statistics for CD34+/CD38- cells: Percentage from total 
CD34+ cells – LSC sub-study Full Analysis Set
Table 14.2-29.2 Descriptive Statistics for number of events sorted in CD34+/CD38-
cells – LSC sub-study Full Analysis Set
Table 14.2-29.3 Ph+ by HIS status, in CD34+/CD38- cells – LSC sub-study Full 
Analysis Set
Table 14.2-29.4 Descriptive statistics of Ph+ in CD34+/CD38- cells– LSC sub-study 
Full Analysis Set
Table 14.2-29.5 BCR-ABL by RT-PCR status, in CD34+/CD38- cells – LSC sub-
study Full Analysis Set
Table 14.2-30.1 Descriptive Statistics for Immunophenotypically aberrant CD34+ 
cells: Percentage from total CD34+ cells –LSC sub-study Full Analysis Set
Table 14.2-30.2 Descriptive Statistics for number of events sorted in 
Immunophenotypically aberrant CD34+ cells – LSC sub-study Full Analysis 
Set
Table 14.2-30.3 Ph+ by HIS status, in Immunophenotypically aberrant CD34+ cells 
– LSC sub-study Full Analysis Set
Table 14.2-30.4 Descriptive statistics of Ph+ in Immunophenotypically aberrant
CD34+ cells– LSC sub-study Full Analysis Set
Table 14.2-30.5 BCR-ABL by RT-PCR status, in Immunophenotypically aberrant
CD34+ cells – LSC sub-study Full Analysis Set
Table 14.2-31.1 Descriptive Statistics for Immunophenotypically aberrant CD34-
cells: Percentage from total CD34+ cells – LSC sub-study Full Analysis Set
Table 14.2-31.2 Descriptive Statistics for number of events sorted in 
Immunophenotypically aberrant CD34- cells- LSC sub-study Full Analysis 
Set
Table 14.2-31.3 Ph+ by HIS status, in Immunophenotypically aberrant CD34- cells –
LSC sub-study Full Analysis Set
Table 14.2-31.4 Descriptive statistics of Ph+ in Immunophenotypically aberrant 
CD34- cells– LSC sub-study Full Analysis Set
Table 14.2-31.5 BCR-ABL by RT-PCR status, in Immunophenotypically aberrant 
CD34- cells – LSC sub-study Full Analysis Set


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Table 14.2-32.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by duration of prior exposure to Imatinib -  
Full Analysis Set
Table 14.2-32.1.1 Raw cumulative incidence of MMR during pre-randomization 
Induction/Consolidation phase by by prior Imatib treatment duration – LSC 
sub-study Full Analysis Set
Table 14.2-32.2 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
Full Analysis Set, randomized to ARM 2
Table 14.2-32.2.1 Raw cumulative incidence of MMR during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2
Table 14.2-32.3 Raw cumulative incidence of MMR during re-treatment phase by 
prior Imatib treatment duration – Subset of Full Analysis Set entering the re-
treatment phase
Table 14.2-33.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration - Full 
Analysis Set
Table 14.2-33.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration – LSC sub-
study Full Analysis Set
Table 14.2-33.2 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
Full Analysis Set, randomized to ARM 2
Table 14.2-33.2.1 Raw cumulative incidence of MR 4.0 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2
Table 14.2-33.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by
prior Imatib treatment duration – Subset of Full Analysis Set entering the re-
treatment phase
Table 14.2-34.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration - Full 
Analysis Set
Table 14.2-34.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase by prior Imatib treatment duration – LSC sub-
study Full Analysis Set
Table 14.2-34.2 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
Full Analysis Set, randomized to ARM 2
Table 14.2-34.2.1 Raw cumulative incidence of MR 4.5 during post-randomization 
consolidation phase (ARM 2) by prior Imatib treatment duration - Subset of  
LSC sub-study Full Analysis Set  , randomized to ARM 2
Table 14.2-34.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by 
prior Imatib treatment duration – Subset of Full Analysis Set entering the re-
treatment phase
Section 14.3 – Safety data


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Table 14.3-1.1 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation– Safety Set
Table 14.3-1.1.1 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation– LSC sub-study Safety Set
Table 14.3-1.2 Duration of exposure to study treatment during post-randomization 
Consolidation phase (ARM 2) - Subset of Safety Set randomized to Arm 2
Table 14.3-1.2.1 Duration of exposure to study treatment during post-randomization 
Consolidation phase (ARM 2) - Subset of LSC sub-study Safety Set 
randomized to Arm 2
Table 14.3-1.1.3 Duration of exposure to study treatment during re-treatment phase –
Subset of Safety Set entering the re-treatment phase
Table 14.3-1.1.21 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation phase, by stable MR4.0 at 24 months and halving 
time - Safety Set
Table 14.3-1.1.22 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation phase, by stable MR4.0 by 24 months and halving 
time - Safety Set
Table 14.3-2.1 Relative dose intensity and average daily dose during pre-
randomization Induction/Consolidation phase – Safety Set
Table 14.3-2.1.1 Relative dose intensity and average daily dose during pre-
randomization Induction/Consolidation phase – LSC sub-study Safety Set
Table 14.3-2.2 Relative dose intensity and average daily dose during post-
randomization consolidation phase (ARM 2) – Subset of Safety Set 
randomized to Arm 2
Table 14.3-2.2.1 Relative dose intensity and average daily dose during post-
randomization consolidation phase (ARM 2) – Subset of LSC sub-study 
Safety Set randomized to Arm 2
Table 14.3-2.3 Relative dose intensity and average daily dose during re-treatment 
phase – Subset of Safety Set entering the re-treatment phase
Table 14.3-3.1 Dose reduction and interruption during pre-randomization 
Induction/Consolidation phase - Safety Set
Table 14.3-3.1.1 Dose reduction and interruption during pre-randomization 
Induction/Consolidation phase – LSC sub-study Safety Set
Table 14.3-3.2 Dose reduction and interruption during post-randomization 
consolidation phase (ARM 2) – Subset of Safety Set randomized to Arm 2
Table 14.3-3.2.1 Dose reduction and interruption during post-randomization 
consolidation phase (ARM 2) – Subset of LSC sub-study Safety Set 
randomized to Arm 2
Table 14.3-3.3 Dose reduction and interruption during re-treatment phase – Subset of 
Safety Set entering the re-treatment phase
Table 14.3-4.1 Concomitant medication by ATC class and preferred term during pre-
randomization Induction/Consolidation phase Full Analysis Set
Table 14.3-4.1.1 Concomitant medication by ATC class and preferred term during
pre-randomization Induction/Consolidation phase LSC sub-study Full 
Analysis Set


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Table 14.3-4.2 Concomitant medication by ATC class and preferred term during 
post-randomization consolidation phase (ARM 2)– Subset of Full Analysis 
Set randomized to Arm 2
Table 14.3-4.2.1 Concomitant medication by ATC class and preferred term during 
post-randomization consolidation phase (ARM 2)– Subset of LSC sub-study 
Full Analysis Set randomized to Arm 2
Table 14.3-4.3 Concomitant medication by ATC class and preferred term during 
TFR phase – Subset of Full Analysis Set entering the TFR phase
Table 14.3-4.4 Concomitant medication by ATC class and preferred term during re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase
Table 14.3-5.1.1 Hematology shift table based on CTCAE grade during Pre-
Randomization pre-randomization Induction/Consolidation –Full Analysis 
Set
Table 14.3-5.1.2 Hematology shift table based on CTCAE grade during post-
randomization consolidation phase (ARM 2)– Subset of Full Analysis Set 
randomized to Arm 2
Table 14.3-5.1.3 Hematology shift table based on CTCAE grade during re-treatment 
phase – Subset of Full Analysis Set entering the re-treatment phase
Table 14.3-5.1.4 Hematology shift table based on CTCAE grade during whole study
period – Full Analysis Set
Table 14.3-5.1.5 Hematology shift table based on CTCAE grade during re-treatment 
phase, SDV sensitivity   – Subset of Full Analysis Set entering the re-
treatment phase
Table 14.3-5.1.6 Hematology shift table based on CTCAE grade during whole study 
period , SDV sensitivity– Full Analysis Set
Table 14.3-5.2.1 Biochemistry shift table based on CTCAE grade during post-
randomization consolidation phase (ARM 2)– Subset of Full Analysis Set 
randomized to Arm 2
Table 14.3-5.2.2 Biochemistry shift table based on CTCAE grade during re-
treatment phase– Subset of Full Analysis Set entering the re-treatment phase
Table 14.3-5.2.3 Biochemistry shift table based on CTCAE grade during whole 
study period – Full Analysis Set
Table 14.3-5.2.4 Biochemistry shift table based on CTCAE grade during re-
treatment phase, SDV sensitivity– Subset of Full Analysis Set entering the re-
treatment phase
Table 14.3-5.2.5 Biochemistry shift table based on CTCAE grade during whole 
study period, SDV sensitivity – Full Analysis Set
Table 14.3-6.1.1 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during post-randomization consolidation phase 
(ARM 2)– Subset of Full Analysis Set randomized to Arm 2
Table 14.3-6.1.2 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase
Table 14.3-6.1.3 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period –Full Analysis Set


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Table 14.3-6.1.4 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase
Table 14.3-6.1.5 Hematology shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period, SDV sensitivity –Full 
Analysis Set
Table 14.3-6.2.1 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during post-randomization consolidation phase 
(ARM 2) – Subset of Full Analysis Set randomized to Arm 2
Table 14.3-6.2.2 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase
Table 14.3-6.2.3 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period –Full Analysis Set
Table 14.3-6.2.4 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase
Table 14.3-6.2.5 Biochemistry shift table based on normal range for parameters with 
no defined CTCAE grades during whole study period, SDV sensitivity –Full 
Analysis Set
Table 14.3-7.1 ECG shift table based on notable values during Pre-randomization 
Induction Consolidation–Full Analysis Set
Table 14.3-7.2 ECG shift table based on notable values during post-randomization 
consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
Arm 2
Table 14.3-7.3 ECG shift table based on notable values during re-treatment phase –
Subset of Full Analysis Set entering the re-treatment phase
Table 14.3-7.4 Notable ECG values during pre-randomization Ind/Cons –Full 
Analysis Set
Table 14.3-7.5 Notable ECG values during post-randomization consolidation phase 
(ARM 2)– Subset of Full Analysis Set randomized to Arm 2
Table 14.3-7.6 Notable ECG values during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase
Table 14.3-7.7 ECG shift table based on notable values during re-treatment phase, 
SDV sensitivity – Subset of Full Analysis Set entering the re-treatment phase
Table 14.3-7.8 Notable ECG values during re-treatment phase, SDV sensitivity –
Subset of Full Analysis Set entering the re-treatment phase
Table 14.3-8.1 Echocardiography assessment at baseline – Full Analysis Set
Table 14.3-8.2 Echocardiography shift table based on overall interpretation - Full 
Analysis Set
Table 14.3-8.3 Echocardiography shift table based on overall interpretation, SDV 
sensitivity - Full Analysis Set
Table 14.3-9.1 Summary statistics of total cholesterol, HDL, LDL, glucose, 
microalbumin and HbA1c over Induction/Consolidation phase – Full 
Analysis Set


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Table 14.3-9.2.1 Total cholesterol shift table based on specific levels during 
Induction Consolidation  – Full Analysis Set
Table 14.3-9.2.2 Total cholesterol shift table based on specific levels during TFR 
phase  – Subset of Full Analysis Set entering the TFR phase
Table 14.3-9.2.3 Total cholesterol shift table based on specific levels during Re-
treatment phase  – Subset of Full Analysis Set entering the Re-treatment 
phase
Table 14.3-9.2.4 Total cholesterol shift table based on specific levels during TFR 
phase, SDV sensitivity  – Subset of Full Analysis Set entering the TFR phase
Table 14.3-9.2.5 Total cholesterol shift table based on specific levels during Re-
treatment phase, SDV sensitivity  – Subset of Full Analysis Set entering the 
Re-treatment phase
Table 14.3-10.1.1 Fasting glucose shift table based on specific levels during 
Induction Consolidation – Full Analysis Set
Table 14.3-10.1.2 Fasting glucose shift table based on specific levels during TFR 
phase  – Subset of Full Analysis Set entering the TFR phase
Table 14.3-10.1.3 Fasting glucose shift table based on specific levels during Re-
treatment phase  – Subset of Full Analysis Set entering the Re-treatment 
phase
Table 14.3-10.1.4 Fasting glucose shift table based on specific levels during TFR 
phase, SDV sensitivity   – Subset of Full Analysis Set entering the TFR phase
Table 14.3-10.1.5 Fasting glucose shift table based on specific levels during Re-
treatment phase, SDV sensitivity   – Subset of Full Analysis Set entering the 
Re-treatment phase
Table 14.3-11.1 Vital Signs during Induction Consolidation – Full Analysis Set
Table 14.3-11.2 Vital Signs during TFR phase – Subset of Full Analysis Set entering 
the TFR phase
Table 14.3-11.3 Vital Signs during Re-treatment phase  – Subset of Full Analysis Set 
entering the Re-treatment phase
Table 14.3-11.4 Vital Signs during TFR phase, SDV sensitivity – Subset of Full 
Analysis Set entering the TFR phase
Table 14.3-11.5 Vital Signs during Re-treatment phase, SDV sensitivity – Subset of 
Full Analysis Set entering the Re-treatment phase
Table 14.3-12.1 Survival follow-up – Full Analysis Set
Table 14.3-12.2 Survival follow-up, SDV sensitivity  – Full Analysis Set
Table 14.3-13.1 Safety follow-up – Full analysis Set
Table 14.3-13.2 Safety follow-up, SDV sensitivity  – Full analysis Set
Section 14.3.1 – Displays of adverse events
Figure 14.3.1-1.1 Kaplan-Meier analysis of time-to-first CVEs during the pre-
randomization Induction/Consolidation phase – Full Analysis Set
Figure 14.3.1-1.2 Kaplan-Meier analysis of time-to-first CVEs during the post-
randomization consolidation phase (ARM 2) – Subset of Full Analysis Set 
randomized to Arm 2


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Figure 14.3.1-1.3 Kaplan-Meier analysis of time-to-first CVEs during the the TFR 
phase – Subset of Full Analysis Set entering the TFR phase
Figure 14.3.1-1.4 Kaplan-Meier analysis of time-to-first CVEs during the re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase
Figure 14.3.1-2.1 Number of sorted events by HIS CD34+/CD38+ cells
Figure 14.3.1-2.2 Number of sorted events by PCR CD34+/CD38+ cells
Figure 14.3.1-3.1 Number of sorted events by HIS CD34+/CD38- cells
Figure 14.3.1-3.2 Number of sorted events by PCR CD34+/CD38- cells
Figure 14.3.1-4.1 Number of sorted events by HIS Immunophenotypically aberrant 
CD34+ cells
Figure 14.3.1-4.2 Number of sorted events by PCR Immunophenotypically aberrant 
CD34+ cells
Figure 14.3.1-5.1 Number of sorted events by HIS Immunophenotypically aberrant 
CD34- cells
Figure 14.3.1-5.2 Number of sorted events by PCR Immunophenotypically aberrant 
CD34- cells
Figure 14.3.1-6.1 Number of HIS+ subjects CD34+/CD38+ cells – LSC substudy 
Full Analysis Set
Figure 14.3.1-6.2 Number of PCR subjects CD34+/CD38+ cells – LSC substudy 
Full Analysis Set
Figure 14.3.1-7.1 Number of HIS+ subjects CD34+/CD38- cells – LSC substudy 
Full Analysis Set
Figure 14.3.1-7.2 Number of PCR subjects CD34+/CD38- cells – LSC substudy Full 
Analysis Set
Figure 14.3.1-8.1 Number of HIS+ subjects Immunophenotypically aberrant CD34+ 
cells – LSC substudy Full Analysis Set
Figure 14.3.1-8.2 Number of PCR subjects Immunophenotypically aberrant CD34+ 
cells – LSC substudy Full Analysis Set
Figure 14.3.1-9.1 Number of HIS+ subjects Immunophenotypically aberrant CD34-
cells – LSC substudy Full Analysis Set
Figure 14.3.1-9.2 Number of PCR subjects Immunophenotypically aberrant CD34-
cells – LSC substudy FAS
Figure 14.3.1-10 Number of patients with detectable LSC – LSC substudy Full 
Analysis Set
Table 14.3.1-1.1 Overall summary of treatment-emergent adverse events occurring 
during pre-randomization Induction/consolidation phase – Full Analysis Set
Table 14.3.1-1.2 Overall summary of treatment-emergent adverse events occurring 
during post-randomization consolidation phase (ARM 2) – Subset of Full 
Analysis Set randomized to Arm 2
Table 14.3.1-1.3 Overall summary of treatment-emergent adverse events occurring 
during re-treatment phase – Subset of Full Analysis Set entering the re-
treatment phase
Table 14.3.1-1.4 Overall summary of adverse events occurring during TFR phase –
Subset of Full Analysis Set entering the TFR phase


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Table 14.3.1-2.1 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during pre-randomization Induction/consolidation phase – Full 
Analysis Set
Table 14.3.1-2.2 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during post-randomization consolidation phase (ARM 2) – Subset 
of Full Analysis Set randomized to Arm 2
Table 14.3.1-2.3 Overall summary of frequent [1] treatment-emergent adverse events 
occurring during re-treatment phase – Subset of Full Analysis Set entering 
the re-treatment phase
Table 14.3.1-2.4 Overall summary of frequent [1] adverse events occurring during 
TFR phase – Subset of Full Analysis Set entering the TFR phase
Table 14.3.1-3.1.1 Treatment Emergent adverse events incidence, regardless of study 
drug relationship, occurring during pre-randomization 
Induction/consolidation phase by system organ class and preferred term -
overall and maximum grade 3/4 – Full Analysis Set
Table 14.3.1-3.1.2 Treatment Emergent adverse events occurence, regardless of 
study drug relationship, occurring during pre-randomization 
Induction/consolidation phase by system organ class and preferred term -
overall and maximum grade 3/4 – Full Analysis Set
Table 14.3.1-3.2.1 Treatment Emergent adverse events incidence, regardless of study 
drug relationship, occurring during post-randomization consolidation phase 
(ARM 2) by system organ class and preferred term - overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
Table 14.3.1-3.2.2 Treatment Emergent adverse events occurence, regardless of 
study drug relationship, occurring during post-randomization consolidation 
phase (ARM 2) by system organ class and preferred term - overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
Table 14.3.1-3.3.1 Treatment-emergent adverse events incidence, regardless of study 
drug relationship, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase
Table 14.3.1-3.3.2 Treatment-emergent adverse events occurrence, regardless of 
study drug relationship, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase
Table 14.3.1-3.4.1 Adverse events incidence, regardless of study drug relationship, 
by system organ class and preferred term during TFR phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase
Table 14.3.1-3.4.2 Adverse events occurrence, regardless of study drug relationship, 
by system organ class and preferred term during TFR phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase
Table 14.3.1-3.5.1 Frequent [1] Treatment Emergent adverse events incidence, 
regardless of study drug relationship occurring during pre-randomization 
Induction/consolidation phase by system organ class and preferred term -
overall and maximum grade 3/4 – Full Analysis Set


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Table 14.3.1-3.5.2 Frequent [1] Treatment Emergent adverse events incidence, 
regardless of study drug relationship occurring during post-randomization 
consolidation phase (ARM 2) by system organ class and preferred term-
overall and maximum grade 3/4  – Subset of Full Analysis Set randomized to 
Arm 2
Table 14.3.1-3.5.3 Frequent [1] Treatment Emergent adverse events incidence, 
regardless of study drug relationship occurring during re-treatment phase by 
system organ class and preferred term- overall and maximum grade 3/4  –
Subset of Full Analysis Set entering the re-treatment phase
Table 14.3.1-3.5.4 Frequent [1] adverse events incidence, regardless of study drug 
relationship occurring during TFR phase by system organ class and preferred 
term - overall and maximum grade 3/4 – Subset of Full Analysis Set entering 
the TFR phase
Table 14.3.1-4.1.1 Serious treatment-emergent adverse events incidence, regardless 
of study drug relationship, by system organ class and preferred term during 
pre-randomization Induction/consolidation phase – overall and maximum 
grade 3/4 –Full Analysis Set
Table 14.3.1-4.1.2 Serious treatment-emergent adverse events occurence, regardless 
of study drug relationship, by system organ class and preferred term during 
pre-randomization Induction/consolidation phase – overall and maximum 
grade 3/4 –Full Analysis Set
Table 14.3.1-4.2.1 Serious treatment-emergent adverse events incidence, regardless 
of study drug relationship, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
Table 14.3.1-4.2.2 Serious treatment-emergent adverse events occurrence, regardless 
of study drug relationship, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
Table 14.3.1-4.3.1 Serious treatment-emergent adverse events incidence, regardless 
of study drug relationship, by system organ class and preferred term during 
re-treatment phase – overall and maximum grade 3/4 – Subset of Full 
Analysis Set entering the re-treatment phase
Table 14.3.1-4.3.2 Serious treatment-emergent adverse events occurrence, regardless 
of study drug relationship, by system organ class and preferred term during 
re-treatment phase – overall and maximum grade 3/4 – Subset of Full 
Analysis Set entering the re-treatment phase
Table 14.3.1-4.4.1 Serious adverse events incidence, regardless of study drug 
relationship, by system organ class and preferred term during TFR phase –
overall and maximum grade 3/4 – Subset of Full Analysis Set entering the 
TFR phase
Table 14.3.1-4.4.2 Serious adverse events occurence, regardless of study drug 
relationship, by system organ class and preferred term during TFR phase –
overall and maximum grade 3/4 – Subset of Full Analysis Set entering the 
TFR phase
Table 14.3.1-4.5.1 Frequent [1] Serious Treatment Emergent adverse events 
incidence, regardless of study drug relationship occurring during pre-


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randomization Induction/consolidation phase by system organ class and 
preferred term - overall and maximum grade 3/4 – Full Analysis Set
Table 14.3.1-4.5.2 Frequent [1] Serious Treatment Emergent adverse events 
incidence, regardless of study drug relationship occurring during post-
randomization consolidation phase (ARM 2) by system organ class and 
preferred term - overall and maximum grade 3/4  – Subset of Full Analysis 
Set randomized to Arm 2
Table 14.3.1-4.5.3 Frequent [1] Serious Treatment Emergent adverse events 
incidence, regardless of study drug relationship occurring during re-treatment 
phase by system organ class and preferred term - overall and maximum grade 
3/4  – Subset of Full Analysis Set entering the re-treatment phase
Table 14.3.1-4.5.4 Frequent [1] Serious adverse events incidence, regardless of study 
drug relationship  occurring during TFR phase by system organ class and 
preferred term - overall and maximum grade 3/4  – Subset of Full Analysis 
Set entering the TFR phase
Table 14.3.1-4.6.1 Serious treatment-emergent adverse events incidence, suspected 
to be study drug related, by system organ class and preferred term during pre-
randomization Induction/consolidation phase  – overall and maximum grade 
3/4 –Full Analysis Set
Table 14.3.1-4.6.2 Serious treatment-emergent adverse events occurence, suspected 
to be study drug related, by system organ class and preferred term during pre-
randomization Induction/consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set
Table 14.3.1-4.7.1 Serious treatment-emergent adverse events incidence, suspected 
to be study drug related, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
Table 14.3.1-4.7.2 Serious treatment-emergent adverse events occurrence, suspected 
to be study drug related, by system organ class and preferred term during 
post-randomization consolidation phase (ARM 2) – overall and maximum 
grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
Table 14.3.1-4.8.1 Serious treatment-emergent adverse events incidence, suspected 
to be study drug related, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase
Table 14.3.1-4.8.2 Serious treatment-emergent adverse events occurrence, suspected 
to be study drug related, by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase
Table 14.3.1-4.9.1 Serious adverse events incidence, suspected to be study drug 
related, by system organ class and preferred term during TFR phase – overall 
and maximum grade 3/4 – Subset of Full Analysis Set entering the TFR 
phase
Table 14.3.1-4.9.2 Serious adverse events occurrence, suspected to be study drug 
related, by system organ class and preferred term during TFR phase – overall 
and maximum grade 3/4 – Subset of Full Analysis Set entering the TFR 
phase


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Table 14.3.1-5.1.1 Treatment-emergent adverse events incidence leading to study 
drug discontinuation by system organ class and preferred term during pre-
randomization Induction/Consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set
Table 14.3.1-5.1.2 Treatment-emergent adverse events occurence leading to study 
drug discontinuation by system organ class and preferred term during pre-
randomization Induction/Consolidation phase – overall and maximum grade 
3/4 –Full Analysis Set
Table 14.3.1-5.2.1 Treatment-emergent adverse events incidence leading to study 
drug discontinuation by system organ class and preferred term during post-
randomization phase (ARM 2) – overall and maximum grade 3/4 – Subset of 
Full Analysis Set randomized to Arm 2
Table 14.3.1-5.2.2 Treatment-emergent adverse events occurrence leading to study 
drug discontinuation by system organ class and preferred term during post-
randomization phase (ARM 2)– overall and maximum grade 3/4 – Subset of 
Full Analysis Set randomized to Arm 2
Table 14.3.1-5.3.1 Treatment-emergent adverse events incidence leading to study 
drug discontinuation by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase
Table 14.3.1-5.3.2 Treatment-emergent adverse events occurrence leading to study 
drug discontinuation by system organ class and preferred term during re-
treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the re-treatment phase
Table 14.3.1-6.1.1 Treatment-emergent adverse events incidence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during pre-randomization Induction/ consolidation phase  – overall and 
maximum grade 3/4 –Full Analysis Set
Table 14.3.1-6.1.2 Treatment-emergent adverse events occurrence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during pre-randomization Induction/consolidation phase – overall and 
maximum grade 3/4 –Full Analysis Set
Table 14.3.1-6.2.1 Treatment-emergent adverse events incidence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during post-randomization consolidation phase (ARM 2) – overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
Table 14.3.1-6.2.2 Treatment-emergent adverse events occurrence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during post-randomization consolidation phase (ARM 2) – overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
Table 14.3.1-6.3.1 Treatment-emergent adverse events incidence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 
term during re-treatment phase – overall and maximum grade 3/4 – Subset of 
Full Analysis Set entering the re-treatment phase
Table 14.3.1-6.3.2 Treatment-emergent adverse events occurrence requiring dosage 
adjustment or temporarily interruption by system organ class and preferred 


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term during re-treatment phase – overall and maximum grade 3/4 – Subset of 
Full Analysis Set entering the re-treatment phase
Table 14.3.1-6.4.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, by specific group and preferred term 
during Pre-randomization Induction/consolidation phase –by treatment arm,
overall and maximum grade 3/4 – Full Analysis Set
Table 14.3.1-6.4.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, by specific group and preferred term
during Pre-randomization Induction/consolidation phase – by treatment arm, 
overall and maximum grade 3/4 –Full Analysis Set
Table 14.3.1-6.5.1 Treatment-emergent adverse events of interest incidence by 
specific group and preferred term during post-randomization consolidation 
phase (ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis 
Set randomized to Arm 2
Table 14.3.1-6.5.2 Treatment-emergent adverse events of interest occurrence, by  
specific group and preferred term during post-randomization consolidation 
phase (ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis 
Set randomized to Arm 2
Table 14.3.1-6.6.1 Treatment-emergent adverse events of interest incidence by 
specific group and preferred term during re-treatment phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment 
phase
Table 14.3.1-6.6.2 Treatment-emergent adverse events of interest occurrence by 
specific group and preferred term during re-treatment phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment 
phase
Table 14.3.1-6.7.1 Adverse events of interest incidence by specific group and 
preferred term during TFR phase – overall and maximum grade 3/4 – Subset 
of Full Analysis Set entering the TFR phase
Table 14.3.1-6.7.2 Adverse events of interest occurrence by specific group and 
preferred term during TFR phase – overall and maximum grade 3/4 – Subset 
of Full Analysis Set entering the TFR phase
Table 14.3.1-7.1.1 Treatment Emergent adverse events of interest incidence, 
regardless of study drug relationship, by specific group and preferred term 
and by cardiovascular risk factors during Pre-randomization 
Induction/consolidation phase – by treatment arm, overall and maximum 
grade 3/4 – Full Analysis Set
Table 14.3.1-7.1.2 Treatment Emergent adverse events of interest occurrence, 
regardless of study drug relationship, by specific group and preferred term 
and by cardiovascular risk factors during Pre-randomization 
Induction/consolidation phase – by treatment arm, overall and maximum 
grade 3/4 –Full Analysis Set
Table 14.3.1-7.2.1 Treatment-emergent adverse events of interest incidence,
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 
cardiovascular risk factor– overall and maximum grade 3 or 4 – Subset of 
Full Analysis Set randomized to Arm 2


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Table 14.3.1-7.2.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 
cardiovascular risk factor – overall and maximum grade 3 or 4 – Subset of 
Full Analysis Set randomized to Arm 2
Table 14.3.1-7.3.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during re-treatment phase, by specific 
group and preferred term, and by cardiovascular risk factor – Subset of Full 
Analysis Set entering the re-treatment phase
Table 14.3.1-7.3.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during re-treatment phase, by specific 
group and preferred term, and by cardiovascular risk factor – Subset of Full 
Analysis Set entering the re-treatment phase
Table 14.3.1-7.4.1 Adverse events of interest incidence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
cardiovascular risk factor – Subset of Full Analysis Set entering the TFR 
phase
Table 14.3.1-7.4.2 Adverse events of interest occurrence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
cardiovascular risk factor – Subset of Full Analysis Set entering the TFR 
phase
Table 14.3.1-7.5.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during pre-randomization 
Induction/consolidation phase, by specific group and preferred term and by 4 
cardiovascular risk factors – overall and maximum grade 3/4  –Full Analysis 
Set
Table 14.3.1-7.5.2 Treatment-emergent adverse events of interest occurence, 
regardless of study drug relationship, during pre-randomization 
Induction/consolidation phase, by specific group and preferred term and by 4 
cardiovascular risk factors – overall and maximum grade 3/4 –Full Analysis 
Set
Table 14.3.1-7.6.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 4 
categories of cardiovascular risk factors– overall and maximum grade 3 or 4 
– Subset of Full Analysis Set randomized to Arm 2
Table 14.3.1-7.6.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during post-randomization 
consolidation phase (ARM 2), by specific group and preferred term, and by 4 
categories of cardiovascular risk factors – overall and maximum grade 3 or 4 
– Subset of Full Analysis Set randomized to Arm 2
Table 14.3.1-7.7.1 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, during re-treatment phase, by specific 
group and preferred term, and by 4 categories of cardiovascular risk factors –
Subset of Full Analysis Set entering the re-treatment phase
Table 14.3.1-7.7.2 Treatment-emergent adverse events of interest occurrence, 
regardless of study drug relationship, during re-treatment phase, by specific 


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group and preferred term, and by 4 categories of cardiovascular risk factors–
Subset of Full Analysis Set entering the re-treatment phase
Table 14.3.1-7.8.1 Adverse events of interest incidence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
4 categories of cardiovascular risk factors – Subset of Full Analysis Set 
entering the TFR phase
Table 14.3.1-7.8.2 Adverse events of interest occurrence, regardless of study drug 
relationship, during TFR phase, by specific group and preferred term, and by 
4 categories of cardiovascular risk factors– Subset of Full Analysis Set 
entering the TFR phase
Table 14.3.1-9.1 On treatment deaths, by system organ class and preferred term 
during pre-randomization Induction/Consolidation phase - Safety Set
Table 14.3.1-9.2 On treatment deaths, by system organ class and preferred term 
during post-randomization consolidation phase (ARM 2) – Subset of Safety 
Set randomized to Arm 2
Table 14.3.1-9.3  On treatment deaths, by system organ class and preferred term 
during re-treatment phase – Subset of Safety Set entering the re-treatment 
phase
Table 14.3.1-10.1.1 Cardiac and vascular adverse events of interest, incidence, by 
treatment arm during the pre-randomization induction/consolidation phase -
Full Analysis Set
Table 14.3.1-10.1.2 Cardiac and vascular adverse events of interest, occurence, by 
treatment arm during the pre-randomization induction/consolidation phase -
Full Analysis Set
Table 14.3.1-10.2.1 Cardiac and vascular adverse events of interest incidence, during 
the post-randomization consolidation phase (ARM 2) - Subset of Full 
Analysis Set randomized to Arm 2
Table 14.3.1-10.2.2 Cardiac and vascular adverse events of interest occurrence, 
during the post-randomization consolidation phase (ARM 2) - Subset of Full 
Analysis Set randomized to Arm 2
Table 14.3.1-10.3.1 Cardiac and vascular adverse events of interest, incidence, by 
treatment arm during the re-treatment phase – Subset of Full Analysis Set 
entered re-treatment phase
Table 14.3.1-10.3.2 Cardiac and vascular adverse events of interest, occurence, by 
treatment arm during the re-treatment phase - Subset of Full Analysis Set 
entered re-treatment phase
Table 14.3.1-10.4.1 Cardiac and vascular adverse events of interest, incidence, by 
treatment arm during the TFR phase – Subset of Full Analysis Set entered 
TFR phase
Table 14.3.1-10.4.2 Cardiac and vascular adverse events of interest, occurence, by 
treatment arm during the TFR phase - Subset of Full Analysis Set entered 
TFR phase
Table 14.3.1-10.5 Relationship between cardiac and vascular adverse events of 
interest with total cholesterol values - Full Analysis Set
Table 14.3.1-10.6 Relationship between cardiac and vascular adverse events of 
interest with glycemic values - Full Analysis Set


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Table 14.3.1-11.1.1 Kaplan-Meier estimate of time-to-first CVEs during the pre-
randomization induction/consolidation phase – Full analysis set
Table 14.3.1-11.1.2 Kaplan-Meier estimate of time-to-first CVEs during the post-
randomization consolidation phase (ARM 2)– Subset of Full Analysis Set 
patients randomized on Arm 2
Table 14.3.1-11.2 Kaplan-Meier estimate of time-to-first CVEs during the re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase
Table 14.3.1-12.1 Medical history by system organ class and preferred term- Full 
Analysis Set
Table 14.3.1-13.1 Prior exposure to imatinib before screening, MMR, age, and Sokal 
by LSC detection category - LSC sub-study Full Analysis Set
Table 14.3.1-13.2.1 Percentage from total CD34+ cells, CD34+/CD38+ cells -
Subgroup of LSC sub-study Full Analysis Set, LSC detected
Table 14.3.1-13.2.2 Percentage from total CD34+ cells, CD34+/CD38- cells -
Subgroup of LSC sub-study Full Analysis Set, LSC detected
Table 14.3.1-13.2.3 Percentage from total CD34+ cells, Immunophenotypically 
aberrant CD34+ cells - Subgroup of LSC sub-study Full Analysis Set, LSC 
detected
Table 14.3.1-13.2.4 Percentage from total CD34+ cells, Immunophenotypically 
aberrant CD34 negative cells - Subgroup of LSC sub-study Full Analysis Set, 
LSC detected
Table 14.3.1-13.3.1 Percentage of Ph+ cells, CD34+/CD38- cells - Subgroup of LSC 
sub-study Full Analysis Set, LSC detected
Table 14.3.1-13.3.2 Percentage of Ph+ cells, CD34+/CD38- cells - Subgroup of LSC 
sub-study Full Analysis Set, LSC detected
Table 14.3.1-13.3.3 Percentage of Ph+ cells, Immunophenotypically aberrant CD34+ 
cells - Subgroup of LSC sub-study Full Analysis Set, LSC detected
Table 14.3.1-13.3.4 Percentage of Ph+ cells, Immunophenotypically aberrant CD34 
negative cells - Subgroup of LSC sub-study Full Analysis Set, LSC detected
Table 14.3.1-13.4 Total Percentage of CD34+ cells- Subgroup of LSC sub-study Full 
Analysis Set, LSC detected
Table 14.3.1-13.5 LSC detection - LSC sub-study Full Analysis Set
Section 14.3.2 – Listings of deaths, other serious and significant adverse events
Listing 14.3.2-1.1 Listing of deaths – Full Analysis Set
Listing 14.3.2-1.2 Listing of deaths SDV sensitivity – Full Analysis Set
Listing 14.3.2-2.1    Listing of adverse events of special interest – Full Analysis Set
Listing 14.3.2-2.2   Listing of adverse events leading to study drug discontinuation –
Full Analysis Set
Listing 14.3.2-2.3   Listing of adverse events leading to study drug discontinuation 
during re-treatment phase – Subset of Full Analysis Set entering the re-
treatment period
Section 14.3.3 – Narratives of deaths, other serious and significant adverse 
events (non statistics and programming deliverables)
Section 14.3.4 – Abnormal laboratory value listings


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Listing 14.3.4-1.1   Listing of abnormal hematology laboratory value – Full Analysis 
Set
Listing 14.3.4-2.1   Listing of abnormal biochemistry laboratory value – Full 
Analysis Set
Section 16 – Appendices
Section 16.1 – Study information
Section 16.1.6 – Listing of patients receiving test drug(s)/investigational 
product(s) from specific batches where more than one batch was 
used
Section 16.1.7 – Randomization scheme and codes (subject identification and 
treatment assigned)
Listing 16.1.7-1.1 Randomization schemes - Randomized patients
Section 16.1.9 – Documentation of statistical methods
Listing 16.1.9.1 Raw Statistical output from Demographic and characteristics at 
baseline– Full Analysis Set
Listing 16.1.9.1.1 Raw Statistical output from Demographic and characteristics at 
baseline– LSC sub-study Full Analysis Set
Listing 16.1.9.2 Raw Statistical output from History of prior Imatinib therapy – Full 
Analysis Set
Listing 16.1.9.2.1 Raw Statistical output from History of prior Imatinib therapy –
LSC sub-study Full Analysis Set
Listing 16.1.9.3    Raw Statistical output from Cardiovascular risk factors at baseline 
– Full Analysis Set
Listing 16.1.9.4.1   Raw Statistical output from Molecular response MR4.0 at 12 
months of TFR–Subset of Full Analysis Set entering the TFR phase
Listing 16.1.9.4.2   Raw Statistical output from Molecular response MR4.0 at 12 
months of TFR–Subset of Per Protocol Analysis Set entering the TFR phase
Listing 16.1.9.5.1   Raw Statistical output from Kaplan-Meier analysis of treatment-
free survival during the TFR phase – Subset of Full Analysis Set entering the 
TFR phase
Listing 16.1.9.5.2   Raw Statistical output from Kaplan-Meier analysis of treatment-
free survival during the TFR phase – Subset of Per Protocol Analysis Set 
entering the TFR phase
Listing 16.1.9.5.3   Raw Statistical output from Kaplan-Meier analysis of overall 
survival from Randomization–Randomized Set
Listing 16.1.9.5.4   Raw Statistical output from Kaplan-Meier analysis of 
progression-free survival during the TFR phase – Subset of Full Analysis Set 
entering the TFR phase
Listing 16.1.9.6.1   Raw Statistical output from Kaplan-Meier estimate of time-to-
first CVEs during the pre-randomization induction/consolidation phase – Full 
analysis set
Listing 16.1.9.6.2   Raw Statistical output from Kaplan-Meier estimate of time-to-
first CVEs during the post-randomization consolidation phase (ARM 2)–
Subset of Full Analysis Set patients randomized on Arm 2


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Listing 16.1.9.6.3   Raw Statistical output from Kaplan-Meier estimate of time-to-
first CVEs during the re-treatment phase – Subset of Full Analysis Set 
entering the re-treatment phase
Section 16.2 – Patient data listings
Listing 16.2-1.1 Enrolled patients
Section 16.2.1 – Discontinued subjects
Listing 16.2.1-1.1 Treatment and study completion - Safety Set
Listing 16.2.1-1.2 Study discontinuation – Full Analysis Set
Listing 16.2.1-1.3
Screen failures (All subjects enrolled)
Section 16.2.2 – Protocol deviations
Listing 16.2.2-1.1 Protocol deviations – Enrolled patients
Section 16.2.3 – Patients excluded from the efficacy analysis
Listing 16.2.3-1.1 Analysis set –  All patients
Section 16.2.4 – Demographics and data at screening
Listing 16.2.4-1.1 Demographic data – Full Analysis Set
Listing 16.2.4-2.1 Family history – Full Analysis Set
Listing 16.2.4-2.2 Disease history– Full Analysis Set
Listing 16.2.4-3.1 Disease history I– Full Analysis Set
Listing 16.2.4-3.2   Disease history II– Full Analysis Set
Listing 16.2.4-3.3   Medical history/current medical condition – Full Analysis Set
Listing 16.2.4.4    Cardiovascular risk factors at baseline for patients with not 
evaluable CV risk factor, Full Analysis Set
Section 16.2.5 – Compliance and/or drug concentration data if available (including 
Bioanalytical Data Report)
Listing 16.2.5-1.1 Dosage administration records – Full Analysis Set
Section 16.2.6 – Individual efficacy response data
Listing 16.2.6-1.1 BCR-ABL(IS) ratio and molecular responses during 
Induction/Consolidation and post-randomization consolidation phase (ARM 
2) – Full Analysis Set
Listing 16.2.6-1.2 BCR-ABL(IS) ratio and molecular responses during TFR phase –
Subset of Full Analysis Set entering the TFR phase
Listing 16.2.6-1.3 BCR-ABL(IS) ratio and molecular responses during re-treatment 
phase – Subset of Full Analysis Set entering the re-treatment phase
Listing 16.2.6-2.1 Criteria of successful TFR – Subset of Full Analysis Set entering 
the TFR phase
Listing 16.2.6-3.1 Assessment of progression-free survival during the TFR phase –
Subset of Full Analysis Set entering the TFR phase
Listing 16.2.6-3.2 Assessment of treatment-free survival during the TFR phase –
Subset of Full Analysis Set entering the TFR phase
Listing 16.2.6-3.3 Assessment of overall survival From Randomization –
Randomized set


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Listing 16.2.6-3.4 Assessment of relapse and treatment status during the TFR phase 
–Subset of Full Analysis Set entering the TFR phase and relapsed
Listing 16.2.6-4.1    WBC and molecular response in patients with WBC increase 
(CTCAE grade>G1) – Full Analysis Set
Listing 16.2.6-5.1   Individual Efficacy data, Molecular response – Full Analysis Set
Listing 16.2.6-5.2   Individual Efficacy data, Bone-marrow I – Full Analysis Set
Listing 16.2.6-5.3   Individual Efficacy data, Bone -marrow II – Full Analysis Set
Listing 16.2.6-6.1.1 Total percentage of CD34+ cells – LSC sub-study Full Analysis 
Set
Listing 16.2.6-6.2.1 Percentage of cells from total CD34 positive– LSC sub-study 
Full Analysis Set
Listing 16.2.6-6.3.1 Number of events sorted– LSC sub-study Full Analysis Set
Listing 16.2.6-6.4.1 Ph+ by HIS– LSC sub-study Full Analysis Set
Listing 16.2.6-6.5.1 BCR-ABL by RT-PCR– LSC sub-study Full Analysis Set
Section 16.2.7 – Adverse event listings
Listing 16.2.7-1.1 All adverse events – Full Analysis Set
Listing 16.2.7-2.1 Serious adverse events Full Analysis Set
Listing 16.2.7-2.2 Adverse events leading to study drug discontinuation – Full 
Analysis Set
Listing 16.2.7-2.3 Adverse events of interest – Full Analysis Set
Listing 16.2.7-3.1 CV risk factors, Nilotinib exposure, glucose and total cholesterol 
rates for patients with cardiac and vascular adverse events of interest, Full 
Analysis Set
Listing 16.2.7-3.2 Cardiac and vascular adverse events of interest, Full Analysis Set
Listing 16.2.7-3.3 Outcomes and subsequent concomitant medications for patients 
with cardiac adverse events of interest, Full Analysis Set
Listing 16.2.7-3.4 Outcomes and subsequent concomitant medications for patients 
with vascular adverse events of interest, Full Analysis Set
Section 16.2.8 – Laboratory measurements
Listing 16.2.8-1.1  Hematology laboratory values and normal ranges – Full Analysis 
Set
Listing 16.2.8-2.1 Biochemistry laboratory values and normal ranges – Full Analysis 
Set
Listing 16.2.8-3.1 Hematological data and molecular response in patients with 
absolute blasts higher than normal ranges, Full Analysis Set
Listing 16.2.8-3.2 Hematological data and molecular response in patients with 
absolute metamyelocytes higher than normal ranges, Full Analysis Set
Section 16.2.9 – Vital signs, physical findings and other observations related to 
safety listings
Listing 16.2.9-1.1    Vital signs – Full Analysis Set
Listing 16.2.9-2.1    Electrocardiograms – Full Analysis Set
Listing 16.2.9-2.2    Echocardiography – Full Analysis Set


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Listing 16.2.9-3.1    Concomitant medications – Full Analysis Set
Listing 16.2.9- 3.2   Prohibited concomitant medications – Full Analysis Set
Listing 16.2.9-4.1     Prior Imatinib therapy– Full Analysis Set
Listing 16.2.9-4.2     Prior antineoplastic therapy, other than Imatinib – Full Analysis 
Set
Listing 16.2.9-5.1    Survival follow-up– Full Analysis set
Listing 16.2.9-5.2    Safety follow-up– Full Analysis set
Listing 16.2.9-6    Prior imatinib exposure – LSC sub-study Full Analysis Set


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Section 10 
Table 10-1 Analysis sets – All patients 
                                                     All patients
                                                         N=xx         
Analysis set                                            n (%)                 
_________________________________________________________________________________________________
Screened patients 
xx (xx.x)
Screened successfully 
xx (xx.x)
Re-screened
xx (xx.x)
Screen Failures
xx (xx.x)
Enrolled patients                                    xx (xx.x)       
  Randomized patients*                                 xx (xx.x)       
  Not Randomized patients                             xx (xx.x) 
Full Analysis Set (FAS)*      
xx (xx.x)
  Randomized patients*                                xx (xx.x)       
  Not Randomized patients*                             xx (xx.x) 
Safety Set*                                          xx (xx.x)  
Per Protocol Analysis Set*     
xx (xx.x)  
- Randomized patients are all patients meeting eligibility criteria for randomization 
(i.e. achieved a sustained MR4.0 for at least 12 months in the Induction/Consolidation phase 
of the study).
- Full Analysis Set (FAS) comprises all subjects who are enrolled, excluding patients with PD 
severity codes: 0, 8.
- Safety Set consists of all patients who received at least one dose of study drug, excluding 
patients with PD severity codes: 0, 5, 8.
- Per Protocol Analysis Set (PPS) comprises all subjects who are enrolled without major protocol 
deviation (PD severity codes: 0, 1, 5, 8).
* Patients without major PD.
Source: Post-text table 14.1-2.3




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Table 10-3 Demographic and characteristics at baseline – Full Analysis Set
Characteristics
at baseline 
Arm 1
N=xx
...
N=xx
Total
N=xx
Comparison$
p-value#
Age at baseline visit(Years) -
n (%) 
  < 65            
  >= 65  
  Missing       
xx (xx.x)
xx (xx.x)
xx
...
xx (xx.x)
xx (xx.x)
xx
0.xxx
Age at baseline visit (Years) 
  n               
  Mean            
  SD              
  25th Percentile 
  Median          
  75th Percentile 
  Min-Max           
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
...
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
0.xxx
0.xxx
Gender - n (%)
  Female 
  Male 
  Missing         
xx (xx.x)
xx (xx.x)
xx
...
xx (xx.x)
xx (xx.x)
xx
0.xxx
If female, child bearing 
potential - n (%)  
  Able to bear children         
  Premenarche                   
  Post menopausal               
  Sterile – of child bearing 
age 
  Missing
         
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xx
...
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xx
0.xxx
Race - n (%)        
  Caucasian       
  Black           
  Asian  
  Native American
  North African descent  
  Unknown       
  Other
  Missing         
  
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
...
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
0.xxx
Body mass index (kg/m2) - n (%)  
  Very severely underweight     
  Severely underweight          
  Underweight                   
  Normal                        
  Overweight                    
  Obese class I                 
  Obese class II                
  Obese class III   
  Missing
     
       
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
...
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
0.xxx
Body mass index (kg/m2) 
  n               
  Mean            
xxx
xx.x
...
xxx
xx.x
0.xxx
0.xxx


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Characteristics
at baseline 
Arm 1
N=xx
...
N=xx
Total
N=xx
Comparison$
p-value#
  SD              
  25th Percentile 
  Median          
  75th Percentile 
  Min-Max
                
x.xx
xx.x
xx.x
xx.x
xx-xx
x.xx
xx.x
xx.x
xx.x
xx-xx
ECOG performance 
  Status (WHO) - n (%)   
   0                   
   1                   
   2                   
   3                   
   4
   Missing  
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
...
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
0.xxx
Family history - n (%) 
   Diabetes
   Hypertension
   Dyslipidemia
   Cardiac events
   Cerebrovascular events
   Peripheral arterial disease
   Missing   
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
...
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
Smoking history - n (%) 
   No                  
   Yes                 
   Ex-smoker        
   Missing   
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
...
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
0.xxx
If ex-smoker, time since 
stopped smoking (months)
  n               
  Mean            
  SD              
  25th Percentile 
  Median          
  75th Percentile 
  Min-Max                
If smoker or ex-smoker, use 
of tobacco product in the 
past month - n (%) 
   Cigarettes (including 
roll-ups)
   Cigars
   Tobacco (e.g. pipe)
   Others (e.g. nicotine 
patches, chewing tobacco)
   Missing   
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
...
...
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
0.xxx
0.xxx
- The last available assessment before or at date of start of study trt is taken as 
“baseline”. BMI (kg/m2): very sev. underweight (< 15.0), sev. underweight (>=15.0-<=16.0), 
underweight (>16.0-<=18.5), normal (>18.5-<=25.0), overweight (>25.0-<=30.0), obese: class I 
(>30.0-<=35.0), class II (>35.0-<=40.0) and class III (over 40.0). Time since stopped smoking 
= (date of screen visit – date stopped smoking + 1) / 30.4375. Perc. based on the number of 
pat. Incl. in the analysis pop. (N). $ Comparison Rand. vs Not Rand. # P-value: For cat. var. 
Pearson Chi-square or Fisher’s exact test. For numeric var. independent t-test for means, 
Median test for medians. * p-value<0.05, ** p-value<0.01.
Source: Post-text table: 14.1-3.1


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Table 10-4 Disease history – Full Analysis Set
Disease history
Arm 1
N=xx
...
N=xx
Total
N=xx
Time since initial diagnosis 
(months)
   n                          
   Mean                       
   SD                         
   25th Percentile            
   Median                     
   75th Percentile
   Min-Max            
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
...
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
Time since initial diagnosis (years)
- n (%)[1]
n=xx
n=xx
<2 years
xx (xx.x) 
...
xx (xx.x) 
2 to 4 years
xx (xx.x) 
xx (xx.x) 
4 to 6 years
xx (xx.x) 
xx (xx.x) 
6 to 8 years
xx (xx.x) 
xx (xx.x) 
8 to 10 years
xx (xx.x) 
xx (xx.x) 
10 to 12 years
xx (xx.x) 
xx (xx.x) 
>= 12 years
xx (xx.x) 
xx (xx.x) 
Peripheral blood blasts % at 
diagnosis
   n                   
   Mean                
   SD                  
   25th Percentile     
   Median              
   75th Percentile
   Min-Max
                 
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
...
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
PB eosinophils % at diagnosis
   n                   
   Mean                
   SD                  
   25th Percentile     
   Median              
   75th Percentile
   Min-Max
    
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
...
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
PB basophils % at diagnosis
   n                   
   Mean                
   SD                  
   25th Percentile     
   Median              
   75th Percentile
   Min-Max     
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
...
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
Platelets at diagnosis (10E9/L)
   n                   
   Mean                
   SD                  
   25th Percentile     
   Median              
   75th Percentile
   Min-Max          
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
...
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
Spleen size at diagnosis (cm under 
costal margin)
   n                   
   Mean                
   SD                  
xxx
xx.x
x.xx
xx.x
...
xxx
xx.x
x.xx
xx.x


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   25th Percentile     
   Median              
   75th Percentile
   Min-Max          
xx.x
xx.x
xx.x- xx.x
xx.x
xx.x
xx.x- xx.x
Extramedullary involvement other 
than hepato and/or splenomegaly 
   - n (%)[1]
   Yes   
   No  
n=xx
xx (xx.x)
xx (xx.x)
...
n=xx
xx (xx.x)
xx (xx.x)
Sokal score  
   n               
   Mean            
   SD              
   25th Percentile 
   Median          
   75th Percentile
   Min-Max     
   - n (%)[1]         
   Low risk        
   High risk       
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
n=xx
xx (xx.x)
xx (xx.x)
...
...
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
n=xx
xx (xx.x)
xx (xx.x)
Euro (Hasford) score  
   n                     
   Mean                  
   SD                    
   25th Percentile       
   Median                
   75th Percentile
   Min-Max
            
   - n (%)[1]               
   Low risk              
   Intermediate risk     
   High risk             
xxx       
xx.x      
x.xx      
xx.x      
xx.x      
xx.x
xx.x- xx.x 
           
n=xx      
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
...
          
...
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
n=xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
EUTOS score
   n               
   Mean            
   SD              
   25th Percentile 
   Median          
   75th Percentile
   Min-Max     
   
   - n (%)[1]         
   Low risk        
   High risk       
xxx      
xx.x     
x.xx     
xx.x     
xx.x     
xx.x
xx.x- xx.x    
n=xx     
xx (xx.x)
xx (xx.x)
...
          
...
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
n=xx
xx (xx.x)
xx (xx.x)
Previous progression to AP/BC   
   - n (%)[1]                      
   Yes   
   No  
n=xx     
xx (xx.x)
xx (xx.x)
...
n=xx
xx (xx.x)
xx (xx.x)
Attempt to stop treatment with 
Imatinib
- n (%)[1]                       
   Yes   
   No  
n=xx     
xx (xx.x)
xx (xx.x)
...
n=xx
xx (xx.x)
xx (xx.x)


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- Time since initial diagnosis = (date of the baseline visit - date of initial diagnosis) /30.4375.
- Sokal score: low risk (<0.8), intermediate risk (>=0.8-<=1.2) and high risk (>1.2).
- Euro (Hasford) score: low risk (<=780), intermediate risk (>780-<=1480) and high risk (>1480).
- EUTOS score: low risk (<=87) and high risk (>87).
[1] Percentages over Number of non-missing.
Source: Post-text table: 14.1-4.1
BCR-ABL(IS) ratio at screening 
   - n (%)[1]                       
   BCR-ABL(IS) >1%             
   BCR-ABL(IS) >0.1%  - <= 1%         
   BCR-ABL(IS) >0.01% - <= 0.1%     
   BCR-ABL(IS) <=0.01%            
   Undetectable BCR-ABL          
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
n=xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
BCR-ABL(IS) ratio at Re-screening 
n=xx     
...
n=xx     
- n (%)[1]                       
xx (xx.x)
...     
xx (xx.x)
BCR-ABL(IS) >1%  
xx (xx.x)
...     
xx (xx.x)
           ...
...
...
...


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Table 10-5 Duration of exposure to study treatment during pre-randomization 
Induction/Consolidation Safety Set
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not 
Randomized
N=xx
Total
N=xx
Exposure (months) 
- n (%)
< 6
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 6 - < 12
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 12 - < 18
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 18 - < =24
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
> 24
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Exposure (months)
n               
xx
xx
xx
xx
xx
Mean
xx.x
xx.x
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Min-Max          xx.x-
xx.x
xx.x-
xx.x
xx.x- xx.x
xx.x- xx.x
xx.x-
xx.x
- Exposure (months) = (date of last administration – date of first administration in 
Induction/Consolidation phase + 1)/30.4375.
- Safety Set consists of all patients who received at least one dose of study drug, excluding 
patients with PD severity codes (0, 5, 8).
Source: Post-text table: 14.3-1.1
Table 10-6 Duration of exposure to study treatment during post-
randomization Consolidation phase (ARM 2) - Subset of Safety Set 
randomized to Arm 2
<< Programming note: Same shell as table 10-6.1 with arm 2 only. 
Use <6, >=6 to <=12 and >12 categories.
Footnote:
- Exposure (months) = (date of last administration – date of first administration in post-
randomization consolidation phase + 1)/30.4375.
- Safety Set consists of all patients who received at least one dose of study drug, excluding 
patients with PD severity codes (0, 5, 8).
Source: Post-text table: 14.3-1.2


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Table 11-1 Raw cumulative incidence of MR 4.0 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set  
Arm 1
...
Total
N=xx
N=xx
N=xx
Major molecular response at baseline 
Number of responders
xx
...
xx
Percentage (95% CI)
xx (xx.x, xx.x)
...
xx (xx.x, xx.x)
Cumulative major molecular response up to 3 
months (Day 91)
Cumulative number of responders
xx
...
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
...
xx (xx.x, xx.x)
Cumulative major molecular response up to 6 
months (Day 183)
Cumulative number of responders
xx
...
xx
...
...
...
...
Cumulative major molecular response up to 9 
months (Day 274)
...
...
...
...
Cumulative major molecular response up to 12 
months (Day 365)
...
...
...
...
Cumulative major molecular response up to 15 
months (Day 457)
...
...
...
...
Cumulative major molecular response up to 18 
months (Day 548)
...
...
...
...
Cumulative major molecular response up to2 
21 months (Day 639)
...
...
...
...
Cumulative Major molecular response up to 24 
months (Day 731)
...
...
...
...
- Percentage based on the number of patients in the analysis population (N).
- Confidence interval calculated as per Clopper-Pearson exact method.
Source: Post-text table: 14.2-7.1
Table 11-2 Raw cumulative incidence of MR 4.0 during post-
randomization consolidation phase (ARM 2) - Subset of Full 
Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 11-1 for ARM 2 only>>
Source: Post-text table: 14.2-7.2
Table 11-3 Raw cumulative incidence of MR 4.5 during pre-randomization 
Induction/Consolidation phase – Full Analysis Set  
<< Programming note: Same shell as table 11-1 for MR4.5 >>
Source: Post-text table: 14.2-8.1


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Table 11-4 Raw cumulative incidence of MR 4.5 during post-
randomization consolidation phase (ARM 2) - Subset of Full 
Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 11-2 for MR4.5 >>
Source: Post-text table: 14.2-8.2
Table 11-5 Primary endpoint, Molecular response MR4.0 at 12 months of 
TFR phase–Subset of Full Analysis Set entering the TFR phase
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Number of responders
xx
xx
xx
Percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Comparison Arm 1 vs Arm 2
p-value$
0.xxx*
- Responders= Patients still in TFR with >=MR4.0, without molecular relapse.
- Confidence interval calculated as per Clopper-Pearson exact method.
- Percentage based on the number of patients included in the analysis population 
(N).
- Patients entered TFR considered for percentages denominator.
$ Pearson Chi-square test or Fisher’s exact test depending on the 
crosstabulation frequencies. * p-value<0.05, ** p-value<0.01.
Source: Post-text table: 14.2-2.1.1


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Table 11-6 Secondary endpoint Kaplan-Meier analysis of treatment-free 
survival during the TFR phase – Subset of Full Analysis Set 
entering the TFR phase
KM estimates
Arm 1
Arm 2
Number of patients – n(%)
with events
xx (xx.x)
xx (xx.x)
   Relapse
xx (xx.x)
xx (xx.x)
   Re-treatment with Nilotinib
xx (xx.x)
xx (xx.x)
   Progression to AP-BC
xx (xx.x)
xx (xx.x)
   Death from any cause
xx (xx.x)
xx (xx.x)
   Relapse + Death from any 
cause
xx (xx.x)
xx (xx.x)
   <<Note for programming: add any combination of events occurring on the same date>> 
with censorings
xx (xx.x)
xx (xx.x)
Time to event (months)
25th percentile (95% CI)
xx (xx.x, xx.x)
xx (xx.x xx.x))
Median (95% CI)
xx (xx.x xx.x))
xx (xx.x xx.x))
75th percentile (95% CI)
xx (xx.x xx.x))
xx (xx.x xx.x))
Percentage of patients without 
event –
Estimate  n(%)(95% CI) 
6 months
xx (xx.x) (xx.x, xx.x)
xx (xx.x) (xx.x, xx.x)
12 months
xx (xx.x) (xx.x, xx.x)
xx (xx.x) (xx.x, xx.x)
18 months
xx (xx.x) (xx.x, xx.x)
xx (xx.x) (xx.x, xx.x)
24 months
xx (xx.x) (xx.x, xx.x)
xx (xx.x) (xx.x, xx.x)
30 months
xx (xx.x) (xx.x, xx.x)
36 months
xx (xx.x) (xx.x, xx.x)
- NE: Not Estimable. Patients randomized to Arm 2 have a maximum of 24 months of TFR phase. 
- Event = first occurrence of relapse, re-treatment with nilotinib, progression to AP/BC or 
death for any cause. Censoring rule = patients who did not meet the event are censored at the 
first date occurring between: the last contact date, the end of TFR phase and the date of 
death. Time to event = (date of event – start date of TFR phase + 1)/30.4375. 
- n is the number of patients at risk at the timepoint (i.e. without event and still ongoing). 
The percentage of patients without event and the respective 95% C.I. are estimated from Kaplan 
Meier.
Source: Post-text table:14.2-2.2.1


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Table 11-7 Secondary endpoint, Molecular response 4.0 during post-
randomization consolidation phase (ARM 2) – Subset of Full Analysis Set
randomized to Arm 2
  Arm2
- Rate was computed using time-window as described in the RAP Module 3.
- Percentage based on the number of patients included in the analysis population 
(N).
- Confidence interval calculated as per Clopper-Pearson exact method.
* Nominal visit is according to the CRF record, regardless of time-window derived 
visit.    
<<Programming note: 
-The number of responders at Month x is obtained by counting all patients with a 
response on the last assessment of time-window x.
-The percentage is obtained by dividing the number of responders by N.>>
Source: Post-text table:14.2-4.2.1
N=xx
Rate of major molecular response at 
Baseline 
Number of responders
xx
Response Rate % (95% CI)
xx (xx.x, xx.x)
Rate of major molecular response at 
Month 27
Number of responders
xx
Response Rate % (95% CI)
xx (xx.x, xx.x)
Rate of major molecular response at 
Month 27 (Nominal visit*)
Number of responders
xx
Response Rate % (95% CI)
xx (xx.x, xx.x)
Rate of major molecular response at 
Month 30
...
...
Rate of major molecular response at 
Month 33
...
...
Rate of major molecular response at 
Month 36
...
...
Rate of major molecular response at 
Month 36 (Nominal vist*)
...
...


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Table 11-8 Secondary endpoint, Kaplan-Meier analysis of overall survival 
from Randomization–Randomized Set
KM estimates
Arm 1
Arm 2
Number of patients – n(%)
with events (deaths)
xx (xx.x)
xx (xx.x)
with censorings
xx (xx.x)
xx (xx.x)
Time to event (months)
25th percentile (95% CI)
xx (xx.x, xx.x)
xx (xx.x xx.x))
Median (95% CI)
xx (xx.x xx.x))
xx (xx.x xx.x))
75th percentile (95% CI)
xx (xx.x xx.x))
xx (xx.x xx.x))
Percentage of patients without 
event –
Estimate  n(%)(95% CI) 
6 months
xx (xx.x) (xx.x, xx.x)
xx (xx.x) (xx.x, xx.x)
12 months
xx (xx.x) (xx.x, xx.x)
xx (xx.x) (xx.x, xx.x)
18 months
xx (xx.x) (xx.x, xx.x)
xx (xx.x) (xx.x, xx.x)
24 months
xx (xx.x) (xx.x, xx.x)
xx (xx.x) (xx.x, xx.x)
30 months
xx (xx.x) (xx.x, xx.x)
36 months
xx (xx.x) (xx.x, xx.x)
- NE: Not Estimable. Event = death for any cause.
- Censoring rule = patients who did not meet the event are censored at the first 
date occurring between: 
the last contact   date and the date of death. 
- Time to event = (date of event – Randomization date + 1)/30.4375. 
- n is the number of patients at risk at the timepoint (i.e. without event and 
still ongoing)
- The percentage of patients without event and the respective 95% C.I. are 
estimated from Kaplan Meier.
Source: Post-text table:14.2-2.3


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Table 12-1 Overall summary of treatment-emergent adverse events 
occurring during pre-randomization Induction/consolidation 
phase – Full Analysis Set 
Adverse event category
Arm 1
N=xx
...
N=xx
Total
N=xx
Any adverse events
xx (xx.x)
...
xx (xx.x)
Any AE of special interest
xx (xx.x)
...
xx (xx.x)
Grading of AEs
NCI-CTCAE Grade 4
xx (xx.x)
...
xx (xx.x)
NCI-CTCAE Grade 3
xx (xx.x)
...
xx (xx.x)
NCI-CTCAE Grade 2
xx (xx.x)
...
xx (xx.x)
NCI-CTCAE Grade 1
xx (xx.x)
...
xx (xx.x)
NCI-CTCAE Missing
xx (xx.x)
...
xx (xx.x)
Death
xx (xx.x)
...
xx (xx.x)
AEs suspected to be related to nilotinib
xx (xx.x)
...
xx (xx.x)
AEs leading to study drug discontinuation
xx (xx.x)
...
xx (xx.x)
AEs 
requiring 
dosage 
adjustment 
or 
temporarily interruption
xx (xx.x)
...
xx (xx.x)
Serious AEs
xx (xx.x)
...
xx (xx.x)
Serious AEs suspected to be related to 
nilotinib
xx (xx.x)
...
xx (xx.x)
Serious 
AEs 
leading 
to 
study
drug 
discontinuation
xx (xx.x)
...
xx (xx.x)
- For patient #
, due to reconciliation discrepancies, safety 
database reported AE term “Endometriosis” as a SAE, while in clinical 
database this AE was not recorded as an SAE.
- Only TEAEs from pre-rand. Ind./Cons. phase have been included. A pat. with mult. occur. 
of an AE is counted only once in the AE categ.; Perc. based on the pop. number (N). AESI 
CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) were based on grouped MedDRA terms 
as descr. in the CRS. Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 
months. Patient #
rep. as disc. Ind/Cons phase due to AE “Blast Crisis”-G2, should 
have been reported as disc. Ind/Cons due to Dis. progr. to Blast Crisis, as per Prot. For pat. 
#
 AE “PHLEGMON FOOT - BIG TOE RIGHT” is rep. as PT “Cellulitis” in the AE list. and 
as PT “Osteoarthritis” in the SAE list. PT for the same AE has been wrongly dec. and reconc. 
was not req. a perfect match of the PT. Source: Post-text table: 14.3.1-1.1


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Table 12-2 Overall summary of treatment-emergent adverse events 
occurring during post-randomization consolidation phase (ARM 
2) – Subset of Full Analysis Set randomized to Arm 2
     Arm2
Adverse event category
N=xx
Any adverse events
xx (xx.x)
Any AE of special interest
xx (xx.x)
Grading of AEs
NCI-CTCAE Grade 4
xx (xx.x)
NCI-CTCAE Grade 3
xx (xx.x)
NCI-CTCAE Grade 2
xx (xx.x)
NCI-CTCAE Grade 1
xx (xx.x)
NCI-CTCAE Missing
xx (xx.x)
Death
xx (xx.x)
AEs suspected to be related to nilotinib
xx (xx.x)
AEs leading to study drug discontinuation
xx (xx.x)
AEs requiring dosage adjustment or temporarily interruption
xx (xx.x)
Serious AEs
xx (xx.x)
Serious AEs suspected to be related to nilotinib
xx (xx.x)
Serious AEs leading to study drug discontinuation
xx (xx.x)
- Only treatment emergent adverse events from post-randomization consolidation phase are 
included in this table. A patient with multiple occurrences of an AE is counted only once in 
the AE category. Percentage based on the population number (N). AE of special interest CVEs 
(IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as 
described in the Case Retrieval Sheet.
- Patients randomized to Arm 2 have 12 months of treatment post-randomization and a maximum of 
24 months of re-treatment.
Source: Post-text table: 14.3.1-1.2


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Table 12-3 Overall summary of treatment-emergent adverse events 
occurring during re-treatment phase – Subset of Full Analysis Set 
entering the re-treatment phase
Adverse event category
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Any adverse events
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any AE of special interest
xx (xx.x)
xx (xx.x)
xx (xx.x)
Grading of AEs
NCI-CTCAE Grade 4
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 3
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs suspected to be related to nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs leading to study drug discontinuation
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs 
requiring 
dosage 
adjustment 
or 
temporarily interruption
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs suspected to be related to 
nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious 
AEs 
leading 
to 
study
drug 
discontinuation
xx (xx.x)
xx (xx.x)
xx (xx.x)
- Only treatment emergent adverse events from re-treatment phase are included in this table. A 
patient with multiple occurrences of an AE is counted only once in the AE category. Percentage 
based on the population number (N). AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) 
and CVEs (others) are based on grouped MedDRA terms as described in the Case Retrieval Sheet.
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-
treatment. Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months 
of re-treatment.
Source: Post-text table: 14.3.1-1.3


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Table 12-4 Overall summary of adverse events occurring during TFR 
phase – Subset of Full Analysis Set entering the TFR phase
Adverse event category
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Any adverse events
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any AE of special interest
xx (xx.x)
xx (xx.x)
xx (xx.x)
Grading of AEs
NCI-CTCAE Grade 4
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 3
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs 
suspected
to 
be 
related 
to 
nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
  AE occurring within 30 days after TFR
end
xx (xx.x)
xx (xx.x)
xx (xx.x)
  AE occurring after 30 days after TFR
end
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs suspected to be related to 
nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
- Only adverse events from TFR phase are included in this table. 
- A patient with multiple occurrences of an AE is counted only once in the AE category.
Percentage based on thepopulation number (N). Patients randomized to Arm 1 have 24 months of 
treatment and a maximum of 36 months of re-treatment. Patients randomized to Arm 2 have 36 
months of treatment and a maximum of 24 months of re-treatment. AE of special interest CVEs 
(IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as 
described in the Case Retrieval Sheet.
Source: Post-text table: 14.3.1-1.4


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Table 12-5 Overall summary of frequent [1] treatment-emergent adverse 
events 
occurring 
during 
pre-randomization 
Induction/consolidation phase – Full Analysis Set 
<< Programming note: Same shell as table 12-1   using the following footnotes:
Source: Post-text table: 14.3.1-2.1
[1] Frequent AE defined as an AE present at 5% or more for at least one treatment Arm.
Only treatment emergent adverse events from pre-rand. ind./cons. phase are included in 
this table. A patient with multiple occurrences of an AE is counted only once in the AE 
category. Percentage based on the population number (N). AE of special interest CVEs (IHD), 
CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described in 
the Case Retrieval Sheet.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
Source: Post-text table: 14.3.1-2.1
Table 12-6 Overall summary of frequent [1] treatment-emergent adverse 
events occurring during post-randomization Consolidation phase 
(ARM 2) – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 12-2 adding the following footnote:
[1] Frequent AE defined as an AE present at 5% or more of the ARM2 patients.
Source: Post-text table: 14.3.1-2.2
Table 12-7 Overall summary of frequent [1] treatment-emergent adverse 
events occurring during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 12-3   adding the following footnote:
[1] Frequent AE defined as an AE present at 5% or more for at least one treatment 
Arm.
Source: Post-text table: 14.3.1-2.3
Table 12-8 Overall summary of frequent [1] adverse events occurring 
during TFR phase – Subset of Full Analysis Set entering the TFR 
phase
<< Programming note: Same shell as table 12-4   adding the following footnote:
[1] Frequent AE defined as an AE present at 5% or more for at least one treatment 
Arm.
Source: Post-text table: 14.3.1-2.4


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Table 12-9 Serious treatment-emergent adverse events incidence, 
regardless of study drug relationship, by system organ class and 
preferred term during pre-randomization Induction/consolidation 
phase – overall and maximum grade 3/4 –Full Analysis Set 
Arm 1
N=xxx
...
Total
N=xxx
Primary system 
organ class
Preferred term
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
Any Primary 
system organ 
class
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Cardiac 
disorders
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Angina pectoris
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Bradycardia NOS
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Oedema NOS
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Tachycardia NOS
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
...
- For patient #
, due to reconciliation discrepancies, safety 
database reported AE term “Endometriosis” as a SAE, while in clinical 
database this AE was not recorded as an SAE.
- Only TEAEs from pre-rand. Ind./Cons. phase have been included. Primary SOC presented 
alphab.; PTs are sorted within prim. SOC in desc. freq. of ‘All grades’ column. Perc.  based 
on pop. number (N). Treatment Arm 1/Arm 2: 24/36 months, Re-trt max Arm 1/Arm 2: 36/24 months. 
A pat. with mult. occur. of an AE is counted only once in the AE cat.; A pat. with mult. AEs 
within a prim. SOC is counted only once in the total row. AEs occur. more than 30 days after 
last study trt. exp. date are not summarized. For pat. #
AE “PHLEGMON FOOT - BIG TOE 
RIGHT” is rep. as PT “Cellulitis” in the AE list. and as PT “Osteoarthritis” in the SAE 
listing. PT for the same AE has been wrongly dec. and reconc. was not req. a perfect match of 
the PT. Source: Post-text table 14.3.1-4.1.1                                                        


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Table 12-10
Serious treatment-emergent adverse events incidence, 
regardless of study drug relationship, by system organ class and 
preferred term during post-randomization consolidation phase 
(ARM 2) – overall and maximum grade 3/4 – Subset of Full 
Analysis Set randomized to Arm 2
                                        Arm2                               
                                  
____ N=xxx _________
Primary system organ class                          All grades    Grade 3/4
   Preferred term                                      n (%)        n (%)   
________________________________________________________________________________
Any primary system organ class                       xx (xx.x)     xx (xx.x) 
Cardiac disorders                                    xx (xx.x)     xx (xx.x) 
   Angina pectoris                                    xx (xx.x)     xx (xx.x) 
   Bradycardia NOS                                    xx (xx.x)     xx (xx.x) 
   Oedema NOS                                         xx (xx.x)     xx (xx.x) 
   Tachycardia NOS                                    xx (xx.x)     xx (xx.x) 
           etc.
- Only treatment emergent adverse events from post-rand. cons. phase (ARM 2) are included in 
this table. Primary system organ classes are presented alphabetically; preferred terms are 
sorted within primary system organ class in descending frequency of ‘All grades’ column.
Percentage based on the number of patients included in the analysis population (N).
- Treatment post-randomization Arm 2: 12 months, Re-treatment max Arm 2: 24 months. 
- A patient with multiple occurrences of an AE is counted only once in the AE category.       
- A patient with multiple adverse events within a primary system organ class is counted only 
once in the total row. Adverse events occurring more than 30 days after last study treatment 
exposure date are not summarized.
Source: Post-text table: 14.3.1-4.2.1
Table 12-11
Serious treatment-emergent adverse events incidence, 
regardless of study drug relationship, by system organ class and 
preferred term during re-treatment phase – overall and maximum 
grade 3/4 – Subset of Full Analysis Set entering the re-treatment 
phase
<< Programming note: Same shell as table 12.9 for re-treatment period>>   
  Source: Post-text table: 14.3.1-4.3.1
Table 12-12 Serious adverse events incidence, regardless of study drug 
relationship, by system organ class and preferred term during 
TFR phase – overall and maximum grade 3/4 – Subset of Full 
Analysis Set entering the TFR phase
<< Programming note: Same shell as table 12.9 for TFR and replacing 1st footnote:
- Only adverse events from TFR phase are included in this table.>>
Source: Post-text table: 14.3.1-4.4.1


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Table 12-13 Treatment-emergent adverse events of interest incidence, 
regardless of study drug relationship, by specific group and 
preferred term during Pre-randomization Induction/consolidation 
phase –by treatment arm, overall and maximum grade 3/4 – Full 
Analysis Set
        
Arm 1 
N=xxx
...
N=xxx
Total
N=xxx
Specific group 
Preferred term
All 
grades 
n (%)
Grade
3/4  
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
All AESI
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Group 1
PT1
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
PT2
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
...
Group 2
PT1
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
PT2
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
...
- Only TEAEs from pre-rand. ind./cons. phase have been incl. in this table. Specific groupings 
are pres. alphabetically; PTs are sorted within each group in desc. frequency of ‘All grades’ 
column. Perc. based on the pop. number (N). Trt Arm 1/Arm 2: 24/36 months, Re-trt max Arm 
1/Arm 2: 36/24 months. A patient with mult. occurrences of an AE is counted only once in the 
AE category. A patient with mult. AEs within a group is counted only once in the total row. 
AESI: CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms 
as described in the Case Retrieval Sheet. AEs occurring more than 30 days after last study 
treatment exposure date are not summarized.
Source: Post-text table: 14.3.1-6.4.1


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Table 12-14 Treatment-emergent adverse events of interest incidence by 
specific group and preferred term during post-randomization 
Consolidation phase (ARM 2) – overall and maximum grade 3/4 –
Subset of Full Analysis Set randomized to Arm 2
Specific group
   Preferred term
Arm2
N=xx
All grades
n (%)
Grade 3/4
n (%)
All AESI
xx (xx.x)
xx (xx.x)
Group 1
PT 1
xx (xx.x)
xx (xx.x)
PT 2
xx (xx.x)
xx (xx.x)
ect..
xx (xx.x)
xx (xx.x)
Group 2
PT 1
xx (xx.x)
xx (xx.x)
PT 2
xx (xx.x)
xx (xx.x)
ect..
xx (xx.x)
xx (xx.x)
ect..
- Only TEAEs from post-rand. cons. phase incl. in this table. Specific groups are pres.
alphabetically; PTs are sorted within each group in desc. frequency of ‘All grades’ column. 
Perc. based on the number of patients included in the analysis pop. (N). Trt post-rand. Arm 2: 
12 months, Re-trt max Arm 2: 24 months. A pat. with mult. occurrences of an AE is counted 
only once in the AE category. A pat. with mult. AEs within a group is counted only once in the 
total row. AESI:CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped 
MedDRA terms as described in the Case Retrieval Sheet. AEs occurring more than 30 days after 
last study trt exp. date are not summarized.
Source: Post-text table:  14.3.1-6.5.1


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Table 12-15 Treatment-emergent adverse events of interest incidence by 
specific group and preferred term during re-treatment phase –
overall and maximum grade 3/4 – Subset of Full Analysis Set 
entering the re-treatment phase
Specific 
group
   Preferred 
term
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
All grades
n (%)
Grade 3/4
n (%)
All grades
n (%)
Grade 3/4
n (%)
All grades
n (%)
Grade 3/4
n (%)
All AESI
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Group 1
PT 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
PT 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ect..
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Group 2
PT 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
PT 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ect..
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ect..
- Only TEAEs from re-trt phase are included in this table. Specific groups are alph. 
presented; PTs are sorted within each group in desc. freq. of ‘All grades’ column. Perc. based 
on the number of pat. included in the analysis pop. (N). Trt Arm 1/Arm 2: 24/36 months, Re-trt 
max Arm 1/Arm 2: 36/24 months. A patient with mult. occurrences of an AE is counted only once 
in the AE category. A patient with mult. AEs within a group is counted only once in the total 
row. AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on 
grouped MedDRA terms as described in the Case Retrieval Sheet.AEs occurring more than 30 days 
after last study trt exp. date are not summarized.
Source: Post-text table:  14.3.1-6.6.1
Table 12-16 Adverse events of interest incidence by specific group and 
preferred term during TFR phase – overall and maximum grade 
3/4 – Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as table 12-15 for TFR, using footnotes:
- Only adverse events from TFR phase are included in this table. Specific groups are 
alphabetically presented; preferred terms are sorted within each group in descending frequency 
of ‘All grades’ column. Percentage based on population number (N). Treatment Arm 1/Arm 2: 
24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months.  A patient with multiple occurrences 
of an AE is counted only once in the AE category. A patient with multiple AE within a primary 
system organ class is counted only once in the total row. AE of special interest CVEs (IHD), 
CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described in 
the Case Retrieval Sheet.
Source: Post-text table:  14.3.1-6.7.1
>> 


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Table 12-17 Treatment-emergent adverse events incidence leading to 
study drug discontinuation by system organ class and preferred 
term during pre-randomization Induction/Consolidation phase –
overall and maximum grade 3/4 –Full Analysis Set 
Arm 1
N=xxx
...
N=xxx
Total
N=xxx
Primary system organ 
class
Preferred term
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
Any Primary system 
organ class
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Cardiac disorders
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Angina pectoris
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Bradycardia NOS
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Oedema NOS
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
Tachycardia NOS
xx (xx.x)
xx (xx.x)
...
...
xx (xx.x)
xx (xx.x)
...
- For patient #
, due to reconciliation discrepancies, safety database 
reported AE term “Endometriosis” as a SAE, while in clinical database this AE was 
not recorded as an SAE.
- Only TEAEs from pre-rand. ind./cons. phase have been included. Prim. SOC are presented 
alphab.; PTs are sorted within prim. SOC in descending freq. of ‘All grades’ column. Perc. 
based pop. number (N). Treatment Arm 1/Arm 2: 24/36 months, Re-trt max Arm 1/Arm 2: 36/24 
months. A patient with mult. occur. of an AE is counted only once in the AE category. A 
patient with mult. AEs within a primary SOC is counted only once in the total row. AEs 
occurring more than 30 days after last study trt. exp. date are not summarized.
Pat. #
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have 
been reported as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, 
as per Prot.  Source: Post-text table:  14.3.1-5.1.1


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Table 12-18 Treatment-emergent adverse events incidence leading to 
study drug discontinuation by system organ class and preferred 
term during post-randomizationphase (ARM 2) – overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to 
Arm 2
Arm2
N=xxx
Primary system organ class
Preferred term
All 
grades 
n (%)
Grade
3/4  
n (%)
Any Primary system organ class
xx (xx.x)
xx (xx.x)
Cardiac disorders
xx (xx.x)
xx (xx.x)
Angina pectoris
xx (xx.x)
xx (xx.x)
Bradycardia NOS
xx (xx.x)
xx (xx.x)
Oedema NOS
xx (xx.x)
xx (xx.x)
Tachycardia NOS
xx (xx.x)
xx (xx.x)
...
- Only TEAEs from post-rand. Cons. phase (ARM 2) are included in this table. Primary system 
organ classes are presented alphabetically; preferred terms are sorted within primary system
organ class in descending frequency of ‘All grades’ column. Percentage based on the number  
of patients included in the analysis population (N). Treatment post-randomization Arm 2: 12 
months, treatment free remission max Arm 2: 24 months. A patient with multiple occurrences 
counted only once in the AE category. A patient with multiple AEs within a primary system   
organ class is counted only once in the total row. AEs occurring more than 30 days after    
last study treatment exposure date are not summarized.                                      
Source: Post-text table:  14.3.1-5.2.1
                            
Table 12-19 On treatment deaths, by system organ class and preferred 
term during pre-randomization Induction/Consolidation phase -
Safety Set
Primary system organ class
Principal cause of death
Arm 1
N=xxx
n (%)
...
N=xxx
n (%)
Total
N=xxx
n (%)
Any Primary system organ class
xx (xx.x)
...
xx (xx.x)
Primary system organ class 1
xx (xx.x)
...
xx (xx.x)
  Preferred term 1
xx (xx.x)
...
xx (xx.x)
  Preferred term 2
xx (xx.x)
...
xx (xx.x)
       ...
...
...
...
                                                    
Primary system organ classes are alphabetically presented; preferred terms are sorted within 
primary system organ class in descending frequency.
- Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months.
- Deaths up to 30 days after last study treatment exposure date are all included 
- For patient 
 date of death was imputed to “
”, from the original 
“
” for the purpose of this table only. 
Source: Post-text table:  14.3.1-9.1


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Table 12-20 On treatment deaths, by system organ class and preferred 
term during post-randomization consolidation phase (ARM 2) –
Subset of Safety Set randomized to Arm 2
Primary system organ class
Principal cause of death
Arm 2
N=xxx
n (%)
Any Primary system organ class
xx (xx.x)
Primary system organ class 1
xx (xx.x)
  Preferred term 1
xx (xx.x)
  Preferred term 2
xx (xx.x)
       ...
...
                                                    
- Primary system organ classes are alphabetically presented; preferred terms are sorted within 
primary system organ class in  descending frequency.
- Percentage based on the number of patients included in the analysis population (N).
- Treatment post-randomization Arm 2: 12 months, Re-treatment max Arm 2: 24 months. 
- Deaths up to 30 days after last study treatment exposure date are all included.
Source: Post-text table:  14.3.1-9.2
Table 12-21 On treatment deaths, by system organ class and preferred 
term during re-treatment phase – Subset of Safety Set entering the 
re-treatment phase
<< Programming note: Same shell as table 10-15.1.1 presenting only Arm 1, Arm 2
and Total for Re-treatment>>
Primary system organ classes are alphabetically presented; preferred terms are sorted within 
primary system organ class in  descending frequency.
- Only deaths occurring during the treatment period (between the first day of study drug 
intake and up to 30 days after last study drug intake) are presented. 
- Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months.
Source: Post-text table:  14.3.1-9.3


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Listing 12-1 Listing of deaths – Full Analysis Set
Country/
Center/
Patient/
Arm
Age/
Sex/
Race
Date 
of 
last 
dose
Study 
day of 
last 
dose
Date of 
death
(phase)
Study day 
of death
Number 
days 
since 
last dose
Principal 
cause of death 
reported/ 
Preferred term
XXX/0XXX
/0XXXX/X
XX/X
/XX
DDMMM
YYYY  
xx
DDMMMYYYY 
(IND/CONS1/C
ONS2/TFR/ 
RE-TRT)
xx
xx 
XXXXXXXXXX/XXX
XXXX
XXX/0XXX
/0XXXX/X
XX/X
/XX
DDMMM
YYYY  
xx
DDMMMYYYY 
(IND/CONS1/C
ONS2/TFR/ 
RE-TRT)
xx #
xx *
XXXXXXXXXX/XXX
XXXX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized. Phase: IND = ind. phase (0-12 m), CONS1 = pre-
rand. cons. phase (12-24 m), CONS2 = post-rand. cons. phase (ARM 2)(24–36 m), TFR=treat. free 
remission phase and RE-TRT=re-treat. phase. Phase displayed indicates in which end of phase 
page the death has been recorded as the primary reason to discontinue the study. If missing 
then death has been recorded in survival follow-up CRF pages. Study day relative to the first 
day of treatment (day 1). * event occurred more than 30 days after last study treatment 
exposure date. # Death occurring outside the treatment emergent period
- Number of days since last dose = day of death – day of last dose + 1.
Source: Post-text listing:  14.3.2-1.1


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Figure 11-1 Primary endpoint, Bar plot MR4.0 at 12 months of TFR phase 
–Subset of Full Analysis Set entering the TFR phase
Source: Post-text figure:  14.2-16
Programming Note: Use black color but different patterns for each bar.


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Figure 11-2 Kaplan-Meier analysis of treatment-free survival during the 
TFR phase –Subset of Full Analysis Set entering the TFR phase
Programming note: 
The axis label should “Time since start of TFR phase (months)” 
Months 24-60 for Arm 1, Months 36-60 for Arm 2
Vertical (Y-Axis) label “Prop. of pts. without treatment”
Source: Post-text figure:  14.2-17.2


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3.2
Shells and specifications for Sections 14 and 16 of the CSR
Section 14 – tables, figures and graphs referred to but not included in the 
text
Section 14.1 – Demographic data
Figures (Section 14.1)
Not applicable 
Tables (Section 14.1)
                                                    


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Table 14.1-1.1 Enrollment by country and center – All patients 
Country 
Center
Arm 1
N=xx
Arm 2
N=xx
Randomized 
N=xx
Not Randomized 
N=xx
Not 
treated
Total
N=xx
All countries 
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
Denmark (2)
xxxx
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xxxxx
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
...
France (8)
xxxx
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xxxxx
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
...
- Arm 1: ARM 1: the nilotinib 24 months treatment arm.
- Arm 2: ARM 2: the nilotinib 36 months treatment arm.
- Randomized: Arm 1+ Arm 2.
- Not Randomized: Screened and treated but Not Randomized patients.
- Not Treated: Screen Failures.
The numbers in parentheses provide the number of centers for the country.
<<Programming note: 
The number of centers per country will always be indicated in parenthesis. Percentages are calculated out of the all screened patients>>


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Table 14.1-1.2 Randomization by country and center – Randomized patients 
Country
  Center
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
All countries
xx (xx.x)
xx (xx.x)
xx (xx.x)
Denmark (2)
xxxx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xxxx
xx (xx.x)
xx (xx.x)
xx (xx.x)
France (8)
xxxx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xxxx
xx (xx.x)
xx (xx.x)
xx (xx.x)
Etc..
                                                     
- Arm 1: ARM 1: the nilotinib 24 months treatment arm.
- Arm 2: ARM 2: the nilotinib 36 months treatment arm.
- Randomized: Arm 1+ Arm 2.
- The numbers in parentheses provide the number of centers for the country.
- Percentage is based on N.
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
- Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
<<Programming note: The number of centers per country will always be indicated in parenthesis. Percentages are calculated out of the FAS patients>>


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Table 14.1-1.3
Patient disposition (Screening failures), All patients 
Total
Disposition Reason
N=XXX
_____________________________________________________________________________________
Screened patients 
   XXX (100.0)
Screened successfully  
   ZZZ
Re-screened 
       YYY
Screen Failures 
    FFF
Reason for Screen failure
As per protocol
   XX
Scheduling conflict
     XX
Other
     XX
Inclusion/Exclusion criteria not met
     XX
  
Inclusion Criteria*
xxxxxxxxxx
xx
xxxxxxxxxxx
xx
...
xxxxxxxxxxx
xx
  
Exclusion Criteria*
xxxxxxxxxxx 
    xx
xxxxxxxxxxx 
xx
...
xxxxxxxxxxx
xx
* Patients enrolled but excluded due to Inclusion/Exclusion Criteria.
Multiple reasons for screen failure for patients.


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Programing Note:
Present only specific Incl/Excl criteria text, do not use numbers since ICX may correspond to different text depending on 
Protocol version.
Present Reason for Screen failure Reason for patients enrolled but excluded due to Inclusion/Exclusion Criteria.    
Use intents before labels of subcategories as in the shell.




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Table 14.1-2.2 Patient disposition in each randomized arm – Full Analysis Set
                                           Page 1 on 2
Disposition                                                                       N=xx         
                                                                                  n (%)           
Number of patients with no major deviation to protocol                           xx (xx.x)
Randomized patients                                                              xx (xx.x)
       
  Arm 1 Nilotinib 24-month treatment arm [1]                                    xx (xx.x)  
    Patients completed the consolidation phase [2]                               xx (xx.x)
    Patients discontinued before TFR phase [2]                                   xx (xx.x)       
    Patients entered in the TFR phase [2]                                        xx (xx.x)       
    Patients who completed the TFR phase (36 months) [3]                         xx (xx.x)
   Patients in the TFR phase with 6 months (i.e. 213 days) without relapse [3]
xx (xx.x)
    Patients in the TFR phase with 12 months (i.e. 411 days) without relapse [3] xx (xx.x)
    Patients discontinued TFR phase without entering re-treatment phase [3]      xx (xx.x)
      - entering in survival follow-up period [4]
xx (xx.x)
      - completing the survival follow-up and the 5 years study period [4]
xx (xx.x)
      - completing the survival follow-up before the 5 years study period [4]
xx (xx.x)
      - discontinued from the study without survival follow-up [4]
xx (xx.x) 
    Patients discontinued TFR and entered in the re-treatment phase [3]          xx (xx.x)  
    Patients discontinued the re-treatment phase [5]                             xx (xx.x)  
          - completing the survival follow-up and the 5 years study period [6]
xx (xx.x)
      - completing the survival follow-up before the 5 years study period [6]
xx (xx.x)
      - discontinued from the study without survival follow-up [6]
xx (xx.x) 
    Patients who completed the re-treatment phase [5]                           xx (xx.x)
[1]Percentage based on the number of patients included in the analysis population (N).
[2]Percentage based on the number of patients randomized at each treatment arm.
[3]Percentage based on the number of patients entered in the TFR phase at each treatment arm.
[4]Percentage based on the number of patients discontinued TFR phase without entering in the re-treatment phase. 
[5]Percentage based on the number of patients entered in the re-treatment phase.
[6]Percentage based on the number of patients discontinued the re-treatment phase.
Protocol deviation exlcuding patient from per protocol analysis set is defined as major protocol deviation (PD severity 
codes: 0, 1, 5, 8).
Patient #
 remained in TFR until EoS. EOP TFR was erroneously completed and data not reconciled.


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                                           Page 2 on 2
Disposition                                                                       N=xx         
                                                                                  n (%)           
___________________________________________________________________________________________________________________________
  Arm 2 Nilotinib 36-month treatment arm [1]                                    xx (xx.x)  
  Patients completed the consolidation phase [2]                                 xx(xx.x)
    Patients entered in the TFR phase [2]                                        xx (xx.x)       
    Patients discontinued before TFR phase [2]                                   xx (xx.x)       
    Patients who completed the TFR phase (24 months) [3]                         xx (xx.x)
    Patients in the TFR phase with 6 months (i.e. 213 days) without relapse [3] xx (xx.x)
    Patients in the TFR phase with 12 months (i.e. 411 days) without relapse [3] xx (xx.x)
    Patients discontinued TFR phase without entering re-treatment phase [3]      xx (xx.x)
      - entering in survival follow-up period [4]
xx (xx.x)
      - completing the survival follow-up and the 5 years study period [4]
xx (xx.x)
      - completing the survival follow-up before the 5 years study period [4]
xx (xx.x)
      - discontinued from the study without survival follow-up [4]
xx (xx.x) 
   Patients discontinued TFR and entered in the re-treatment phase [3]          xx (xx.x)  
    Patients discontinued the re-treatment phase [5]                             xx (xx.x)  
      - completing the survival follow-up and the 5 years study period [6]
xx (xx.x)
      - completing the survival follow-up before the 5 years study period [6]
xx (xx.x)
      - discontinued from the study without survival follow-up [6]
xx (xx.x) 
   Patients who completed the re-treatment phase [5]                          xx (xx.x)
[1]Percentage based on the number of patients included in the analysis population (N).
[2]Percentage based on the number of patients randomized at each treatment arm.
[3]Percentage based on the number of patients entered in the TFR phase at each treatment arm.
[4]Percentage based on the number of patients discontinued TFR phase without entering in the re-treatment phase. 
[5]Percentage based on the number of patients entered in the re-treatment phase.
[6]Percentage based on the number of patients discontinued the re-treatment phase.
Protocol deviation exlcuding patient from per protocol analysis set is defined as major protocol deviation (PD severity 
codes: 0, 1, 5, 8).
Patient #
 remained in TFR until EoS. EOP TFR was erroneously completed and data not reconciled.
<<Programming note:
Enrolled patients (who signed IFC and who met IE criteria):  present in IFC dataset (with IFC1D not missing) and IECELI1C=yes in IEC dataset


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Treated patients: at least one piece of data in DAR 
Randomized patients: IECELIC1 (Subject eligible for randomization?)=yes in CRI dataset
Arm 1: RND1C=1  in IVRS dataset
Arm 1 who completed the TFR phase:  RND1C=1  in IVRS dataset, and remaining in TFR up to EOS (ie in CMP, subject has VISNAM1A= V403-EOS and 
SBJCMP1C (Subject completed 5 years study period?)=yes)
Arm 1 who entered the re-treatment phase: RND1C=1  in IVRS dataset, and in CMP, Patient should have taken drug in RT phase.Arm 2: RND1C=2  in IVRS 
dataset
Arm 2 eligible for TFR: RND1C=2  in IVRS dataset, and IECELIC2 (Subject eligible for TFR phas?)=yes in CRI dataset
Arm 2 who completed the TFR phase: RND1C=2  in IVRS dataset, and remaining in TFR up to EOS (ie in CMP, subject has VISNAM1A= V403-EOS and 
SBJCMP1C (Subject completed 5 years study period?)=yes)
Arm 2 who entered the re-treatment phase: RND1C=2  in IVRS dataset,   Patient should have taken drug in RT phase.>>


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Table 14.1-2.2.1 Patient disposition – Enrolled patients in LSC substudy
Disposition                                                                        N=xx         
                                                                                   n (%)           
___________________________________________________________________________________________________________________________
    
Patients enrolled in the induction/consolidation phase                           xx (xx.x) 
Patients Not Randomized 
                           xx (xx.x) 
   
Patients who received at least one dose of nilotinib                            xx (xx.x) 
Randomized patients                                                              xx (xx.x)       
        Nilotinib 24-month treatment arm (Arm 1)                                 xx (xx.x)  
       
        Nilotinib 36-month treatment arm (Arm 2)                                 xx (xx.x)       
Patients with no major deviation to protocol
xx (xx.x)       
- Percentage is based on N
- LSC: Leukemic Stem Cells. Enrolled in LSC are patients signed the LSC ICF.


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Table 14.1-2.3 Analysis sets –All patients  
                                                                         
                                                           All patients
                                                              N=xx         
Analysis set                                                 n (%)                 
_______________________________________________________________________________________________________________________________________
Screened patients 
xx (xx.x)
Screened succesfully                                        xx (xx.x)
Re-screened
xx (xx.x)
Screen failures 
xx (xx.x)
Enrolled patients                                           xx (xx.x)       
  Randomized patients*                                      xx (xx.x)       
  Not Randomized patients
xx (xx.x)    
Enrolled patients (FAS)*                                    xx (xx.x)       
  Randomized patients*                                      xx (xx.x)       
  Not Randomized patients*
xx (xx.x
Safety Set*                                                 xx (xx.x)    
Per Protocol Analysis Set*   
xx (xx.x)
- Randomized patients are all patients meeting eligibility criteria for randomization (i.e. achieved a sustained MR4.0 for at 
least 12 months in the Induction/Consolidation phase of the study).
- Full Analysis Set (FAS) comprises all subjects who are enrolled, excluding patients with PD severity codes: 0, 8.
- Safety Set consists of all patients who received at least one dose of study drug, excluding patients with PD severity 
codes: 0, 5, 8.
Per Protocol Analysis Set (PPS) comprises all subjects who are enrolled without major protocol deviation (PD severity codes: 
0, 1, 5, 8)
* Patients without major PD.


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Table 14.1-2.4 Not Randomized patients - Enrolled patients
* Other reason not related to Molecular response, including: AE, ICF withdrew, PD, lost to follow up, death, etc. 
Total
(N=XX) 
n (%)
Not Randomized Patients 
xx 
Reasons
Patient with last assessment < MR4.0
xx (xx.x)
Patient with < 4 times MR4.0, out of 5 times MR4.0
xx (xx.x)
   Patient with no MR4.0, out of 5 times MR4.0
xx (xx.x)
   Patient with 1 time MR4.0, out of 5 times MR4.0
xx (xx.x)
   Patient with 2 times MR4.0, out of 5 times MR4.0
xx (xx.x)
   Patient with 3 times MR4.0, out of 5 times MR4.0
xx (xx.x)
Patient with < 4 times MR4.0, out of 5 times MR4.0 and last assessment < MR4.0    
xx (xx.x)
   Patient with no MR4.0, out of 5 times MR4.0
xx (xx.x)
   Patient with 1 time MR4.0, out of 5 times MR4.0
xx (xx.x)
   Patient with 2 times MR4.0, out of 5 times MR4.0
xx (xx.x)
   Patient with 3 times MR4.0, out of 5 times MR4.0
xx (xx.x)
Patient with 4 times MR4.0, out of 5 times, MR4.0 but last assessment < MR4.0
xx (xx.x)
Patient with < 4 times MR4.0 out of 5 times
MR4.0, with last assessment MR4.0
xx (xx.x)
Other reason*
xx (xx.x)


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Table 14.1-2.5  Patient disposition, Overall and by year-phase -Enrolled patients 
Disposition 
Reason
Arm 1
N=xx
Arm 2
N=xx
Randomized 
N=xx
Not Randomized 
N=xx
Total
N=xx
Total
Patients enrolled
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients not-treated[1]
   Primary reason for study discontinuation
   Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Abnormal laboratory value(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Abnormal test procedure result(s)  
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Pregnancy                          
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Protocol deviation                 
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Subject withdrew consent           
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Lost to follow-up                  
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Administrative problems            
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Disease progression (CML)          
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Unstable MR4.0                     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   New cancer (CML) therapy           
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients treated [2]
Patients treated
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Discontinued from treatment
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for study discontinuation
   Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
    ...
...
...
...
...
...
   Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Induction-Consolidation 1st year
Patients not-treated[3]
   Primary reason for study discontinuation


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   Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   ...
...
...
...
...
...
   Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients treated [2]
Patients treated
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Discontinued from treatment
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for study discontinuation
   Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
    ...
...
...
...
...
...
   Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Induction-Consolidation 2nd  year (pre-
randomization consolidation)
Patients treated [2]
Patients treated
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Discontinued from treatment
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for study discontinuation
   Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
    ...
...
...
...
...
...
   Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
3rd year of treatment (post-randomization 
consolidation)
Patients treated [2]
Patients treated
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Discontinued from treatment
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for study discontinuation
   Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
    ...
...
...
...
   Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
TFR period
Patients entered TFR 
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
TFR ongoing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)


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Patients Completed TFR 
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Discontinued from TFR
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for study discontinuation
   Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
    ...
...
...
...
...
   Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for study discontinuation
Re-treatment period 
Patients entered re-treatment period  
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients not-treated (during re-treatment) [4]
   Primary reason for study discontinuation
   Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   ...
...
...
...
...
   Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients treated (during re-treatment)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Re-Treatment ongoing #
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Re-treatment completed
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Discontinued from treatment
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for study discontinuation
   Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
    ...
...
...
...
   Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Survival follow-up period 
Patients entered survival follow-up period  
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients followed during survival follow-up
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Survival follow-up ongoing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Survival follow-up completed
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Discontinued from survival follow-up
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for death
   CML
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   Other
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
                                                                                                    
# Patients with treatment ongoing in Re-treatment phase at the time of DBL ddmmmyyyy. 
- Percentage is based on N.
[1] Patients who discontinued study after enrollment without taking study drug.
[2] Patients who discontinued study during Induction/Consolidation phase, having received study drug. 


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[3] Patients who discontinued study after enrollment without taking study drug, during 1st year of 
Induction-Consolidation 
[4] Patients who discontinued study after start of re-treatment without taking study drug.
- Patient #
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been 
reported as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
Patient #
 remained in TFR until EoS. EOP TFR was erroneously completed and data not reconciled.
<<Programming note: 
Sort reason for discontinuation by decreasing frequency >>


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Table 14.1-2.6 Patients discontinued and reason for discontinuation – Full Analysis Set
Disposition
   Reason 
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Patients discontinued at any time-point after 
Randomization
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for discontinuation [1]
Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Abnormal laboratory value(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Abnormal test procedure result(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Pregnancy
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Protocol deviation
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Subject withdrew consent
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Lost to follow-up
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Administrative problems
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Disease progression (CML)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Relapse (Loss of MMR/confirmed loss of MR4.0)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
New cancer (CML) therapy
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Other
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients discontinued before TFR [2]
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for discontinuation 
Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Abnormal laboratory value(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Abnormal test procedure result(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Pregnancy
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Protocol deviation
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Subject withdrew consent
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Lost to follow-up
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Administrative problems
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Disease progression (CML)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Relapse (Loss of MMR/confirmed loss of MR4.0)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
New cancer (CML) therapy
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Other
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)


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Disposition
   Reason 
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Patients entered in the TFR phase
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients discontinued from the TFR phase
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for TFR discontinuation 
Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Abnormal laboratory value(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Abnormal test procedure result(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Pregnancy
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Protocol deviation
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Subject withdrew consent
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Lost to follow-up
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Administrative problems
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Disease progression (CML)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Relapse (Loss of MMR/confirmed loss of MR4.0)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
New cancer (CML) therapy
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Other
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients entered in the re-treatment phase
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients discontinued from the re-treatment phase
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary reason for re-treatment discontinuation 
Adverse event(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Abnormal laboratory value(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Abnormal test procedure result(s)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Pregnancy
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Protocol deviation
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Subject withdrew consent
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Lost to follow-up
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Administrative problems
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Disease progression (CML)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
New cancer (CML) therapy
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Other
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Patients entered in the survival follow up
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)


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- Percentage based on the number of patients included in the analysis population (N).
[1] Primary discontinuation reasons summarized are relative to each phase and thus one patient can have several reasons of 
discontinuation corresponding to discontinuations from different phases.
[2] For treatment Arm 1 patients discontinued before TFR, may occur between Randomization and treatment administration.
- Patient #
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been 
reported as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
Patient #
 remained in TFR until EoS. EOP TFR was erroneously completed and data not reconciled.
<<Programming note:
Patients entered in TFR phase: corresponds to Arm 1 patients randomized (RND1C=1 in IVRS dataset) + Arm 2 patients eligible for TFR phase (RND1C=2 in 
IVRS dataset, and IECELIC2 (Subject eligible for TFR phase?)=yes in CRI dataset)
Patients discontinued from TFR phase: in CMP, subject has VISNAM1A= V401-EOP-TFR + DCNRSN1C for reason for discontinuation from TFR phase
Patients entered in re-treatment phase: in CMP, subject has VISNAM1A=V401-EOP-TFR and RTMTPH1C (Does the subject enter the retreatment phase?)=yes 
Patients discontinued from re-treatment phase: in CMP, subject has VISNAM1A= V402-EOP-RT + DCNRSN1C for reason for discontinuation from re-treatment 
phase.
Sort reasons for discontinuation by descending frequency.>>
Table 14.1-2.6.1 Patients discontinued and reason for discontinuation, SDV sensitivity – Full Analysis Set
<< Programming note: Same shell as table 14.1-2.6, for SDV sensitivity analysis>>
- Percentage based on the number of patients included in the analysis population (N).
[1] Primary discontinuation reasons summarized are relative to each phase and thus one patient can have 
several reasons of discontinuation corresponding to discontinuations from different phases.
[2] For treatment Arm 1 patients discontinued before TFR, may occur between Randomization and 
treatment administration.
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
- Patient #
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been 
reported as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
Patient #
 remained in TFR until EoS. EOP TFR was erroneously completed and data not reconciled.


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Table 14.1-2.7 Summary of TFR phase – Full Analysis Set
TFR 
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Number of patients entering the TFR phase
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 3
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 4
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 5
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 6
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 8
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 10
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 12
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 15
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 18
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 21
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 24
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 27
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 30
xx (xx.x)
xx (xx.x)


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Number of patients in TFR phase at Month 33
xx (xx.x)
xx (xx.x)
Number of patients in TFR phase at Month 36
xx (xx.x)
xx (xx.x)
- Percentage based on the number of patients included in the analysis population (N).
- Patients randomized to Arm 1 have a maximum of 36 months of TFR phase.
- Patients randomized to Arm 2 have a maximum of 24 months of TFR phase.
- Month corresponds to time-window as defined in the RAP Module 3.
Table 14.1-2.7.1 Summary of TFR phase, SDV sensitivity – Full Analysis Set
<< Programming note: Same shell as table 14.1-2.7, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.1-2.8   Summary of re-treatment phase – Full Analysis Set
Re-treatment
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Number of Full Analysis Set entering the re-treatment phase
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Week 6
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 3
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 6
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 9
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 12
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 15
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 18
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 21
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 24
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 27
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 30
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 33
xx (xx.x)
xx (xx.x)
Number of patients in re-treatment phase at Month 36
xx (xx.x)
xx (xx.x)
- Percentage based on the number of patients included in the analysis population (N).
- Patients randomized to Arm 1 have a maximum of 36 months of TFR phase.
- Patients randomized to Arm 2 have a maximum of 24 months of re-treatment phase.
- Week or Month corresponds to time-window as defined in the RAP Module 3.


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Table 14.1-2.8.1 Summary of re-treatment phase, SDV sensitivity – Full Analysis Set
<< Programming note: Same shell as table 14.1-2.8, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.1-2.9 Summary of patients with relapse during the TFR phase but no entering re-treatment phase –-
Subset of Full Analysis Set entering the TFR phase
Relapse
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Number of patients relapse but not enter the re-treatment phase
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Week 6
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 3
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 6
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 9
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 12
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 15
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 18
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 21
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 24
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 27
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 30
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 33
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter re-treatment phase at Month 36
xx (xx.x)
xx (xx.x)
Number of patients relapse but not enter the re-treatment phase immediately,
but entered at re-treatment at a later stage.
xx (xx.x)
xx (xx.x)
xx (xx.x)


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- Percentage based on the number of patients included in the analysis population (N). 
- Patients randomized to Arm 2 have a maximum of 24 months of re-treatment phase.
- Week or Month corresponds to time-window as defined in the RAP Module 3.
- Classification to each specific time window was based on time between Relapse and Re-treatment for patients with Re-
treatment and time between Relapse and Last contact date, for patients with no Re-treatment at all.
     
- Due to the fact that only standard time points presented, any events occurred outside those standard time windows, although 
counted in “relapse but not enter the re-treatment phase” total category, were not presented in the following categories.


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Protocol No CAMN107AIC0
Table 14.1-3.1 Demographic and characteristics at baseline– Full Analysis Set
Characteristics at baseline 
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Comparison$
p-value#
Age at baseline visit(Years) - n (%) 
  < 65            
  >= 65  
  Missing       
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx
0.xxx
Age at baseline visit (Years) 
  n               
  Mean            
  SD              
  25th Percentile 
  Median          
  75th Percentile 
  Min-Max           
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
0.xxx
0.xxx
Gender - n (%)
  Female 
  Male 
  Missing         
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx
0.xxx*
If female, child bearing potential - n (%)  
  Able to bear children                   
  Premenarche                             
  Post menopausal                         
  Sterile – of child bearing age 
  Missing
         
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xx
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xx
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xx
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xx
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xx
0.xxx
Race - n (%)        
  Caucasian       
  Black           
  Asian  
  Native American
  North African descent  
  Unknown       
  Other
  Missing         
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
0.xxx


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Protocol No CAMN107AIC0
Characteristics at baseline 
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Comparison$
p-value#
  
Body mass index (kg/m2) - n (%)  
  Very severely underweight     
  Severely underweight          
  Underweight                   
  Normal                        
  Overweight                    
  Obese class I                 
  Obese class II                
  Obese class III   
  Missing
            
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
0.xxx
Body mass index (kg/m2) 
  n               
  Mean            
  SD              
  25th Percentile 
  Median          
  75th Percentile 
  Min-Max
                
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
0.xxx
0.xxx
ECOG performance 
  Status (WHO) - n (%)   
   0                   
   1                   
   2                   
   3                   
   4
   Missing  
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
0.xxx
Family history - n (%) 
   Diabetes
   Hypertension
   Dyslipidemia
   Cardiac events
   Cerebrovascular events
   Peripheral arterial disease
   Missing   
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx


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Protocol No CAMN107AIC0
Characteristics at baseline 
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Comparison$
p-value#
Smoking history - n (%) 
   No                  
   Yes                 
   Ex-smoker        
   Missing   
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
0.xxx
If ex-smoker, time since stopped smoking 
(months)
  n               
  Mean            
  SD              
  25th Percentile 
  Median          
  75th Percentile 
  Min-Max                
If smoker or ex-smoker, use of tobacco 
product in the past month - n (%) 
   Cigarettes (including roll-ups)
   Cigars
   Tobacco (e.g. pipe)
   Others (e.g. nicotine patches, chewing 
tobacco)
   Missing   
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx-xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
0.xxx
0.xxx
0.xxx
- The last available assessment before or at date of start of study treatment is taken as “baseline” assessment.
- Body mass index (kg/m2): very severely underweight (less than 15.0), severely underweight (>=15.0-<=16.0),
underweight (>16.0-<=18.5), normal (>18.5-<=25.0), overweight (>25.0-<=30.0), obese class I (>30.0-<=35.0), obese class II 
(>35.0-<=40.0) and obese class III (over 40.0).  
- Time since stopped smoking = (date of screening visit – date stopped smoking + 1) / 30.4375.                                
- Percentage based on the number of patients included in the analysis population (N).
$ Comparison Randomized vs Not Randomized. # P-value: For categorical variables Pearson Chi-square test or 
Fisher’s exact test depending on the crosstabulation frequencies. For numeric variables independent t-test for 
means, Median test for medians. * p-value<0.05, ** p-value<0.01.


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<<Programming note: 
Comparison between Randomized and No Randomized group will be done for Demographics and baseline characteristics, History of 
prior Imatinib therapy, Cardiovascular risk factors, using: Pearson’s Chi-square test p-value, or Fisher’s exact test in case 
we have one or more frequencies in the cross-tabulation MR4.0 Yes/No*Randomized/Not Randomized, less than 5 for categorical 
variables, to check correlation between MR4.0 and Randomization group.
For numeric variables, Independent t-test for means (using “Equal” variances or “Unequal” variances depending on Variance test 
result) and Median test for median will be used to test for differences between Randomized and Not Randomized group. 
-Pearson’s Chi-square test p-value will be the first choice for categorical varaibles.
Fisher’s exact test will be used in case we have one or more frequencies in the cross-tabulation Variable*Randomized/Not 
Randomized, less than 5. >>
Table 14.1-3.1.1 Demographic and characteristics at baseline– LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.1-3.1, for LSC sub-study FAS patients >>


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Protocol No CAMN107AIC0
Table 14.1-4.1 Disease history – Full Analysis Set
Disease history
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Time since initial diagnosis (months)
   n                          
   Mean                       
   SD                         
   25th Percentile            
   Median                     
   75th Percentile
   Min-Max            
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
Time since initial diagnosis (years)
- n (%)[1]
n=xx
n=xx
n=xx
n=xx
n=xx
<2 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
2 to 4 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
4 to 6 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
6 to 8 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
8 to 10 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
10 to 12 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 12 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Peripheral blood blasts % at diagnosis
   n                   
   Mean                
   SD                  
   25th Percentile     
   Median              
   75th Percentile
   Min-Max
             
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
PB eosinophils % at diagnosis
   n                   
   Mean                
   SD                  
   25th Percentile     
   Median              
   75th Percentile
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x


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Protocol No CAMN107AIC0
   Min-Max
    
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
PB basophils % at diagnosis
   n                   
   Mean                
   SD                  
   25th Percentile     
   Median              
   75th Percentile
   Min-Max     
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x-
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
Platelets at diagnosis (10E9/L)
   n                   
   Mean                
   SD                  
   25th Percentile     
   Median              
   75th Percentile
   Min-Max          
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
Spleen size at diagnosis (cm under costal margin)
   n                   
   Mean                
   SD                  
   25th Percentile     
   Median              
   75th Percentile
   Min-Max          
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xx.x
xx.x- xx.x
Extramedullary involvement other than hepato and/or 
splenomegaly 
   - n (%)[1]
   Yes   
   No  
n=xx
xx (xx.x)
xx (xx.x)
n=xx
xx (xx.x)
xx (xx.x)
n=xx
xx (xx.x)
xx (xx.x)
n=xx
xx (xx.x)
xx (xx.x)
n=xx
xx (xx.x)
xx (xx.x)
Sokal score  
   n               
   Mean            
   SD              
   25th Percentile 
   Median          
xxx
xx.x
x.xx
xx.x
xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xxx
xx.x
x.xx
xx.x
xx.x
xxx
xx.x
x.xx
xx.x
xx.x


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Protocol No CAMN107AIC0
   75th Percentile
   Min-Max     
   - n (%)[1]         
   Low risk        
   High risk       
xx.x
xx.x- xx.x
n=xx
xx (xx.x)
xx (xx.x)
xx.x
xx.x- xx.x
n=xx
xx (xx.x)
xx (xx.x)
xx.x
xx.x- xx.x
n=xx
xx (xx.x)
xx (xx.x)
xx.x
xx.x- xx.x
n=xx
xx (xx.x)
xx (xx.x)
xx.x
xx.x- xx.x
n=xx
xx (xx.x)
xx (xx.x)
Euro (Hasford) score  
   n                     
   Mean                  
   SD                    
   25th Percentile       
   Median                
   75th Percentile
   Min-Max
            
   - n (%)[1]               
   Low risk              
   Intermediate risk     
   High risk             
xxx       
xx.x      
x.xx      
xx.x      
xx.x      
xx.x
xx.x- xx.x 
           
n=xx      
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xxx       
xx.x      
x.xx      
xx.x      
xx.x      
xx.x
xx.x- xx.x  
          
n=xx      
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xxx       
xx.x      
x.xx      
xx.x      
xx.x      
xx.x
xx.x- xx.x  
          
n=xx      
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xxx       
xx.x      
x.xx      
xx.x      
xx.x      
xx.x
xx.x- xx.x  
          
n=xx      
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
xxx       
xx.x      
x.xx      
xx.x      
xx.x      
xx.x
xx.x- xx.x   
         
n=xx      
xx (xx.x) 
xx (xx.x) 
xx (xx.x)
EUTOS score
   n               
   Mean            
   SD              
   25th Percentile 
   Median          
   75th Percentile
   Min-Max     
   
   - n (%)[1]         
   Low risk        
   High risk       
xxx      
xx.x     
x.xx     
xx.x     
xx.x     
xx.x
xx.x- xx.x     
n=xx     
xx (xx.x)
xx (xx.x)
xxx      
xx.x     
x.xx     
xx.x     
xx.x     
xx.x
xx.x- xx.x    
n=xx     
xx (xx.x)
xx (xx.x)
xxx      
xx.x     
x.xx     
xx.x     
xx.x     
xx.x
xx.x- xx.x   
n=xx     
xx (xx.x)
xx (xx.x)
xxx      
xx.x     
x.xx     
xx.x     
xx.x     
xx.x
xx.x- xx.x       
n=xx     
xx (xx.x)
xx (xx.x)
xxx      
xx.x     
x.xx     
xx.x     
xx.x     
xx.x
xx.x- xx.x   
       
n=xx     
xx (xx.x)
xx (xx.x)
Previous progression to AP/BC   
   - n (%)[1]                      
   Yes   
   No  
n=xx     
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)


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- Time since initial diagnosis = (date of the baseline visit - date of initial diagnosis)/30.4375.
- Sokal score: low risk (<0.8), intermediate risk (>=0.8-<=1.2) and high risk (>1.2).
- Euro (Hasford) score: low risk (<=780), intermediate risk (>780-<=1480) and high risk (>1480).
- EUTOS score: low risk (<=87) and high risk (>87).
[1] Percentages over Number of non-missing.
Table 14.1-4.1.1 Disease history – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.1-4.1, for LSC sub-study FAS patients >>
Attempt to stop treatment with Imatinib
- n (%)[1]                       
   Yes   
   No  
n=xx     
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
BCR-ABL(IS) ratio at screening 
   - n (%)[1]                       
   BCR-ABL(IS) >1%             
   BCR-ABL(IS) >0.1%  - <= 1%           
   BCR-ABL(IS) >0.01% - <= 0.1%     
   BCR-ABL(IS) <=0.01%            
   Undetectable BCR-ABL          
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
BCR-ABL(IS) ratio at Re-screening 
   - n (%)[1]                       
   BCR-ABL(IS) >1%             
   BCR-ABL(IS) >0.1%  - <= 1%           
   BCR-ABL(IS) >0.01% - <= 0.1%     
   BCR-ABL(IS) <=0.01%            
   Undetectable BCR-ABL                                 
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)


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Table 14.1-5.1 History of prior Imatinib therapy – Full Analysis Set
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Comparison$
p-value#
Prior imatinib intake - n (%)
  Yes                      
  Missing      
            
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
0.xxx
Duration of prior exposure (years) 
   - n (%)[1]
    <2                            
    >=2 - <5                     
    >=5  
                         
n=xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
n=xx
xx (xx.x)
xx (xx.x)
xx (xx.x)
0.xxx*
Duration of prior exposure (months)
   n                     
   Mean                  
   SD                    
   25th Percentile       
   Median                
   75th Percentile
   Min-Max            
                       
xxx
xx.x
xx.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
xx.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
xx.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
xx.xx
xx.x
xx.x
xx.x
xx.x- xx.x
xxx
xx.x
xx.xx
xx.x
xx.x
xx.x
xx.x- xx.x
0.xxx
0.xxx
-
Imatinib therapy starting before the date of first Nilotinib intake.
-
Duration of prior exposure (months) = (end date of prior imatinib intake – start date of prior imatinib intake + 
1)/30.4375.
-
[1] Percentages based on the number of patients from the analysis population without missing data (n). 
$ Comparison Randomized vs Not Randomized. 
# p-value: For categorical variables Pearson Chi-square test or Fisher’s exact test depending on the crosstabulation 
frequencies. For numeric variables independent t-test for mean, Median test for medians. 
   * p-value<0.05, ** p-value<0.01.


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<<Programming note: 
Comparison between Randomized and No Randomized group will be done for Demographics and baseline characteristics, History of 
prior Imatinib therapy, Cardiovascular risk factors, using: Pearson’s Chi-square test p-value, or Fisher’s exact test in case 
we have one or more frequencies in the cross-tabulation MR4.0 Yes/No*Randomized/Not Randomized, less than 5 for categorical 
variables, to check correlation between MR4.0 and Randomization group.
For numeric variables, Independent t-test for means (using “Equal” variances or “Unequal” variances depending on Variance test 
result)and Median test for median will be used to test for differences between Randomized and Not Randomized group. 
-Pearson’s Chi-square test p-value will be the first choice for categorical varaibles.
Fisher’s exact test will be used in case we have one or more frequencies in the cross-tabulation Variable*Randomized/Not 
Randomized, less than 5. >>
Table 14.1-5.1.1 History of prior Imatinib therapy – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.1-5.1, for LSC sub-study FAS patients >>


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Table 14.1-5.2 Prior antineoplastic therapy, other than Imatinib, by ATC class and preferred term -  Full Analysis 
Set
Arm 1
N=xx
n (%)
Arm 2
N=xx
n (%)
Randomized
N=xx
n (%)
Not Randomized
N=xx
n (%)
Total
N=xx
n (%)
Any ATC class
-Total
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ATC class 1
-Total
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Preferred term 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Preferred term 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ATC class 2
-Total
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Preferred term 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Preferred term 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
- ATC classes are presented alphabetically; preferred terms are sorted within ATC class by descending frequency. 
- A medication can appear with more than one ATC class.                                                       


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Table 14.1-6.1 Cardiovascular risk factors at baseline – Full Analysis Set
Cardiovascular factors
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Comparison$
p-value#
CV risk factor       – n (%)[1]     
n=xx
n=xx
n=xx
n=xx
n=xx
Very high risk                 
High risk                      
Moderate risk
Low risk                       
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
0.xxx*
- CV risk factors are defined as described in European Guidelines on cardiovascular disease prevention in clinical practice 
(version 2012). European Heart Journal (2012) 33, 1635–1701.
- [1] Percentages over Number of non-missing.
$ Comparison Randomized vs Not Randomized. 
# P-value: For categorical variables Pearson Chi-square test or Fisher’s exact test depending on the 
crosstabulation frequencies. 
* p-value<0.05, ** p-value<0.01.
<<Programming note: 
Comparison between Randomized and No Randomized group will be done for Demographics and baseline characteristics, History of 
prior Imatinib therapy, Cardiovascular risk factors, using: Pearson’s Chi-square test p-value, or Fisher’s exact test in case 
we have one or more frequencies in the cross-tabulation MR4.0 Yes/No*Randomized/Not Randomized, less than 5 for categorical 
variables, to check correlation between MR4.0 and Randomization group.
For numeric variables, Independent t-test for means (using “Equal” variances or “Unequal” variances depending on Variance test 
result) and Median test for median will be used to test for differences between Randomized and Not Randomized group. 
-Pearson’s Chi-square test p-value will be the first choice for categorical varaibles.
Fisher’s exact test will be used in case we have one or more frequencies in the cross-tabulation Variable*Randomized/Not 
Randomized, less than 5. >>


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Table 14.1-6.2 Cardiovascular risk factors (based on medical history, laboratory values and vital signs at 
baseline) – Full Analysis Set
Cardiovascular
   Characteristic
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Medical history – n (%)                                        
CVEs (IHD: Ischemic heart disease)                  
CVEs (PAOD: Peripheral arterial occlusive disease)  
CVEs (ICE: Ischemic cerebrovascular events)         
CVEs (Others)                                       
Hypercholesterolemia                                
Hypertension                                        
Diabetes                                            
At least one CV medical history                      
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Fasting glucose at baseline  – n (%)                           
n=xx
n=xx
n=xx
n=xx
n=xx
5.6 – 6.9 mmol/L 
> 6.9 mmol/L                                                
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Total cholesterol at baseline  – n (%)                         
n=xx
n=xx
n=xx
n=xx
n=xx
> 5.2 mmol/L
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
LDL cholesterol at baseline  – n (%)                           
n=xx
n=xx
n=xx
n=xx
n=xx
> 3.3 mmol/L                                                xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
HDL cholesterol at baseline  – n (%)                           
n=xx
n=xx
n=xx
n=xx
n=xx
<1.3 mmol/L                                                 xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Triglycerides at baseline  – n (%)                             
n=xx
n=xx
n=xx
n=xx
n=xx
> 1.7 mmol/L                                                xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Total cholesterol, LDL, triglycerides and HDL at baseline  –
n (%) *                                                        
n=xx
n=xx
n=xx
n=xx
n=xx
At least one risk factor**                                  xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)


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Blood pressure at baseline    – n (%)> 140/90 mmHg             
n=xx
n=xx
n=xx
n=xx
n=xx
Overall                                     
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Of patient in post-randomization consolidation phase (Arm 
2)                      
xx (xx.x)
xx (xx.x)
NA 
xx (xx.x)
Of patient in TFR phase      
xx (xx.x)
xx (xx.x)
xx (xx.x)
NA 
xx (xx.x)
Of patient in re-treatment phase  
xx (xx.x)
xx (xx.x)
xx (xx.x)
NA 
xx (xx.x)
- The last available assessment before or at date of start of study treatment is taken as “baseline” assessment.
- Blood pressure at baseline (systolic blood pressure > 140mmHg or diastolic blood pressure >90 mmHg).
* number of patients with at least one observation available for total cholesterol, LDL, triglycerides and HDL.
** number of patients with high total cholesterol, high LDL, high triglycerides or low HDL.
- Percentage based on the number of patients without missing data included in the analysis population (N).


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Section 14.2 – Efficacy and other non-safety data (e.g. PK, PK/PD, Health Econ., QoL)
Figures (Section 14.2)


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Figure 14.2-1.1 Box-plot of BCR-ABL ratio (IS) during pre-randomization Induction/Consolidation phase – Full 
Analysis Set
        Time-points over Induction/Consolidation phase
         - The last value of BCR-ABL (IS) ratio per time-window is displayed in this figure.  
<<Programming note:
- Continue for Arm 2, Not Randomized.
- Display LTWBCRIS values on a logarithmic at base 10 scale (after excluding null value)
- Header/title/footer of the figure must not be displayed in the header and footer of the .doc files >>;


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Figure 14.2-1.2 Box-plot of BCR-ABL ratio (IS) during post-randomization Consolidation phase (ARM 2) –
Subset of Full Analysis Set randomized to ARM 2
<<Programming note: 
-Same shell as Box-plot of BCR-ABL ratio (IS) during pre-randomization Induction/Consolidation phase - All treated patients (Figure 14.2-1.1) 
but only for ARM 2, using x-axis label ‘Time-points over post-randomization Consolidation phase (ARM2)’ and Months 27, 30, 33 and 36 as axis 
points.
No need to present Baseline.
Figure 14.2-1.3 Box-plot of BCR-ABL ratio (IS) during TFR phase – Subset of Full Analysis Set entered TFR
<<Programming note: 
-Same shell as Box-plot of BCR-ABL ratio (IS) during pre-randomization Induction/Consolidation phase - All treated patients (Figure 14.2-1.1) 
but for TFR period, using x-axis label ‘Time-points over TFR phase’.
Axis tick points:
Arm1: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 8, Month 10, Month 12, Month 15, then every 3 months until Month 36.
Arm2: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 8, Month 10, Month 12, Month 15, then every 3 months until Month 24.
No need to present Baseline.
Figure 14.2-1.4 Box-plot of BCR-ABL ratio (IS) during re-treatment phase – Subset of Full Analysis Set
entered re-treatment
<<Programming note: 
-Same shell as Box-plot of BCR-ABL ratio (IS) during pre-randomization Induction/Consolidation phase - All treated patients (Figure 14.2-1.1) 
but for re-treatment period, using x-axis label ‘Time-points over Re-treatment phase’.
Axis tick points:
Arm1: Day 1, Week 6, Month 3, Month 6, then every 3 months until M36 
Arm2: Day 1, Week 6, Month 3, Month 6, then every 3 months until M24 
No need to present Baseline.


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Figure 14.2-1.5 Box-plot of BCR-ABL ratio (IS) during TFR phase – , SDV sensitivity Subset of Full Analysis 
Set entered TFR
<< Programming note: Same shell as Figure 14.2-1.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Figure 14.2-1.6 Box-plot of BCR-ABL ratio (IS) during re-treatment phase, SDV sensitivity –Subset of Full 
Analysis Set entered re-treatment
<< Programming note: Same shell as Figure 14.2-1.4, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Figure 14.2-2.1.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
- Full Analysis Set
<< Programming note:
- Display up to Month 24  
- Header/title/footer of the figure must not be displayed in the header and footer of the .doc files , and Months 0, 3,…, 24 as axis points
>>
Figure 14.2-2.1.2 Raw cumulative incidence of MMR during post-randomization Consolidation phase (ARM 2) -
Subset of Full Analysis Set randomized to ARM 2
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during Induction/Consolidation phase (Figure 14.2-2.1.1) but for ARM 2 patients only.>>
Axis title: “Time since study start (months)” and Months 27, 30, 33, 36 as axis points


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Figure 14.2-2.2.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
by halving time of BCR-ABL (IS) ratio - Full Analysis Set
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during Induction/Consolidation phase (Figure 14.2-2.1.1) but done by subgroup of halving time 
of BCR-ABL (IS) ratio.>>
Figure 14.2-2.2.2 Raw cumulative incidence of MMR during post-randomization Consolidation phase (ARM 2) 
by halving time of BCR-ABL (IS) ratio - Subset of Full Analysis Set randomized to ARM 2
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during post-randomization consolidation phase (Figure 14.2-2.1.2) but done by subgroup of 
halving time of BCR-ABL (IS) ratio.>>


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Figure 14.2-2.3.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation 
phase – Full Analysis Set
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase (Figure 14.2-2.1.1) done for MR 4.0.>>
Figure 14.2-2.3.2 Raw cumulative incidence of MR 4.0 during post-randomization Consolidation phase (ARM 2) 
- Subset of Full Analysis Set randomized to ARM 2
<<Programming note: 
-Same shell as Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation phase (Figure 14.2-2.3.1) done for ARM 2
patients only.>>


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Figure 14.2-2.3.11 Raw cumulative incidence of MR 4.0, Randomized vs Not Randomized, during pre-
randomization Induction/Consolidation phase - Full Analysis Set
Figure 14.2-2.4.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation 
phase by halving time of BCR-ABL (IS) ratio - Full Analysis Set
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio 
(Figure 14.2-2.2.1) done for MR 4.0.>>


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Figure 14.2-2.4.2 Raw cumulative incidence of MR 4.0 during post-randomization Consolidation phase (ARM 2) 
by halving time of BCR-ABL (IS) ratio - Subset of Full Analysis Set randomized to ARM 2
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during Induction/Consolidation phase (Figure 14.2-2.4.1) but for ARM 2 patients only.>>
Figure 14.2-2.5.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation 
phase - Full Analysis Set
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase (Figure 14.2-2.1.1) done for MR 4.5.>>
Figure 14.2-2.5.11 Raw cumulative incidence of MR 4.5, Randomized vs Not Randomized, during pre-
randomization Induction/Consolidation phase- Full Analysis Set
<<Programming note: -Same shell as Raw Cumulative incidence of MR 4.0, Randomized vs Not Randomized, during pre-randomization 
Induction/Consolidation phase, All treated patients (Figure 14.2-2.3.11), but for MR 4.5.
Figure 14.2-2.5.2 Raw cumulative incidence of MR 4.5 during post-randomization Consolidation phase (ARM 
2) - Subset of Full Analysis Set randomized to ARM 2
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during post-randomization Consolidation phase (ARM 2) (Figure 14.2-2.1.1) done for MR 4.5.>>
Figure 14.2-2.6.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation phase 
by halving time of BCR-ABL (IS) ratio - Full Analysis Set
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase by halving time of BCR-ABL (IS) ratio 
(Figure 14.2-2.2.1) done for MR 4.5 by subgroup of halving time of BCR-ABL (IS) ratio.>>


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Figure 14.2-2.6.2 Raw cumulative incidence of MR 4.5 during post-randomization Consolidation phase (ARM 2)
by halving time of BCR-ABL (IS) ratio - Subset of Full Analysis Set randomized to ARM 2
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during post-randomization Consolidation phase (ARM 2) by halving time of BCR-ABL (IS) ratio -
Subgroup of All treated patients randomized to ARM 2 (Figure 14.2-2.2.2) done for MR 4.5 >>
Figure 14.2-2.7.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
- Full Analysis Set patients not reaching MMR at baseline
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase (Figure 14.2-2.1.1), performed on the 
subset of subjects not reaching MMR at baseline (i.e. time-to-first MMR not equal to 0). >>
Figure 14.2-2.8.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation 
phase - Full Analysis Set patients not reaching MR 4.0 at baseline
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase (Figure 14.2-2.1.1), performed on the 
subset of subjects not reaching MR 4.0 at baseline (i.e. time-to-first MR 4.0 not equal to 0). >>
Figure 14.2-2.9.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation phase 
- Full Analysis Set patients not reaching MR 4.5 at baseline
<<Programming note: 
-Same shell as Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase (Figure 14.2-2.1.1), performed on the 
subset of subjects not reaching MR 4.5 at baseline (i.e. time-to-first MR 4.5 not equal to 0). >>
Figure 14.2-2.9.2 Raw cumulative incidence of MR 4.5 during post-randomization Induction/Consolidation 
phase (ARM 2)- Subset of Full Analysis Set patients not reaching MR 4.5 at baseline, randomized to 
ARM 2.
<<Programming note: 
-Same shell as Raw cumulative incidence of MR 4.5 during post-randomization Consolidation phase (ARM 2) (Figure 14.2-2.1.2) performed on the 
subset of subjects not reaching MR 4.5 at baseline (i.e. time-to-first MR 4.0 not equal to 0). >>


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Figure 14.2-2.10.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation 
phase by BCR-ABL(IS) ratio at baseline - Full Analysis Set
<< Programming note:
Continue for Arm 2, Not Randomized.
- Same shell as Figure 4.4 made by BCR-ABL(IS) ratio (use MRCATBL = 2 for BCR-ABL(IS) ratio >0.1% - ≤1%, and MRCATBL = 3 for 
BCR-ABL(IS) ratio >0.01% - ≤0.1%)
- Header/title/footer of the figure must not be displayed in the header and footer of the .doc files >>
Figure 14.2-2.10.2 Raw cumulative incidence of MR 4.0 during post-randomization Consolidation phase (ARM 
2) by BCR-ABL(IS) ratio at baseline - Subset of Full Analysis Set randomized to ARM 2.
<< Programming note:
- Same shell as Figure 14.2-2.10.1, but for ARM 2 patients only.
- Header/title/footer of the figure must not be displayed in the header and footer of the .doc files >>


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Figure 14.2-2.11.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation 
phase by BCR-ABL(IS) ratio at baseline - Full Analysis Set
<< Programming note:
- Same shell as Figure 14.2-2.10.1, but on MR 4.5
- Header/title/footer of the figure must not be displayed in the header and footer of the .doc files >>
Figure 14.2-2.11.2 Raw cumulative incidence of MR 4.5 during post-randomization Consolidation phase (ARM 
2) by BCR-ABL(IS) ratio at baseline - Subset of Full Analysis Set randomized to ARM 2.
<< Programming note:
- Same shell as Figure 14.2-2.10.2, but on MR 4.5
- Header/title/footer of the figure must not be displayed in the header and footer of the .doc files >>


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Figure 14.2-2.12.1 Box-plot of BCR-ABL ratio (IS) during pre-randomization Induction/Consolidation phase, 
excluding outliers (BCR-ABL (IS) ratio>10 - Full Analysis Set
         - The last value of BCR-ABL (IS) ratio per time-window is displayed in this figure.  
<< Programming note:
- Continue for Arm 2, Not Randomized.
- Same shell as Figure 4.1 but without outliers
- Add footnote “Outliers with BCR-ABL (IS) ratio higher than 10 are not displayed on this figure.>>
Figure 14.2-2.12.2 Box-plot of BCR-ABL ratio (IS) over post-randomization Consolidation phase (ARM 2), 
excluding outliers (BCR-ABL (IS) ratio>10 - Subset of Full Analysis Set randomized to ARM 2.
<< Programming note:
- Same shell as Figure 14.2-2.12.1, only for ARM 2.
- Header/title/footer of the figure must not be displayed in the header and footer of the .doc files >>
No need to present Baseline.


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Figure 14.2-2.12.3 Overall box-plot of BCR-ABL ratio (IS) during pre-randomization Induction/Consolidation 
phase – Full Analysis Set 
<< Programming note: 
-
X Axis should include: Baseline, Month 3, Month 6,…., Month 24 »» 
-
X axis label : month
 
 m
 
 
 
  
 
 m
 
 
 m
 
m
 
 
 V
 
 
 
 
 
 
 
 
 
 


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Figure 14.2-13.1 Raw cumulative incidence of loss of MMR during TFR – Subset of Full Analysis Set entering 
the TFR phase
<< Programming note: 
Label of axis to change with: “Time since start of TFR phase (months)” >>
-
Axis should go from 0 to month 36 
-
Graph should be presented using 2 different type of lines ARM 1 (dash) / ARM 2 (full line)
Figure 14.2-13.2 Raw cumulative incidence of MMR during re-treatment phase – Subset of Full Analysis Set
entering the re-treatment phase 
<< Programming note: same shell as figure 14.2-13.1 “Time since start of Re-treatment phase (months)” >>
-
Axis should go from 0 to month 36 >>>>
Cumulative % of patients
0
10
20
30
40
50
60
70
80
90
100
Time since study start (months)
0
3
6
9
12
15
18
21
24


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Figure 14.2-13.3 Raw cumulative incidence of loss of MMR during TFR, SDV sensitivity – Subset of Full 
Analysis Set entering the TFR phase
<< Programming note: Same shell as Figure 14.2-13.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Figure 14.2-13.4 Raw cumulative incidence of MMR during re-treatment phase, SDV sensitivity – Subset of 
Full Analysis Set entering the re-treatment phase 
<< Programming note: Same shell as Figure 14.2-13.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Figure 14.2-14.1 Raw cumulative incidence of loss of MR4.0 during TFR phase –Subset of Full Analysis Set 
entering the TFR phase
<< Programming note: same shell as figure 14.2-13.1 but for TFR MR4.0.
-
Label of axis to change with: “Time since start of TFR phase (months)” >>
Figure 14.2-14.2 Raw cumulative incidence of MR4.0 during re-treatment phase – Subset of Full Analysis Set
entering the re-treatment phase
<< Programming note: same shell as figure 14.2-13.2, but for re-treatment MR4.0 >>


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Figure 14.2-14.3 Raw cumulative incidence of loss of MR4.0 during TFR phase, SDV sensitivity –Subset of 
Full Analysis Set entering the TFR phase
<< Programming note: Same shell as Figure 14.2-14.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Figure 14.2-14.4 Raw cumulative incidence of MR4.0 during re-treatment phase, SDV sensitivity – Subset of 
Full Analysis Set entering the re-treatment phase 
<< Programming note: Same shell as Figure 14.2-14.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Figure 14.2-15.1 Raw cumulative incidence of loss of MR4.5 during TFR phase – Subset of Full Analysis Set 
entering the TFR phase with MR4.5
<< Programming note: same shell as figure 14.2-13.1 but for TFR MR4.5>>
Figure 14.2-15.2 Raw cumulative incidence of MR4.5 during re-treatment phase – Subset of Full Analysis Set
entering the re-treatment phase
<< Programming note: same shell as figure 14.2-13.2 but for re-treatment MR4.5>>  


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Figure 14.2-15.3 Raw cumulative incidence of loss of MR4.5 during TFR phase, SDV sensitivity – Subset of 
Full Analysis Set entering the TFR phase with MR4.5
<< Programming note: Same shell as Figure 14.2-15.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Figure 14.2-15.4 Raw cumulative incidence of MR4.5 during re-treatment phase, SDV sensitivity – Subset of 
Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as Figure 14.2-15.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Figure 14.2-16 Bar plot MR4.0 at 12 months of TFR phase –Subset of Full Analysis Set entering the TFR 
phase
Programming Note: Use black color but different patterns for each bar.
Figure 14.2-16.2 Bar plot MR4.0 at month 12 TFR phase , SDV sensitivity –Subset of Full Analysis Set entering 
the TFR phase
<< Programming note: Same shell as Figure 14.2-16, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Figure 14.2-17.1 Kaplan-Meier analysis of progression-free survival during the TFR phase –Subset of Full 
Analysis Set entering the TFR phase
The axis label should “Time since start of TFR phase (months)”
Months 0-36 for Arm 1, Months 0-24 for Arm 2
Vertical (Y-Axis) label “Prop. of pts. without Disease progression”
Figure 14.2-17.2 Kaplan-Meier analysis of treatment-free survival during the TFR phase –Subset of Full Analysis 
Set entering the TFR phase
<< Programming note: same shell as figure 14.2-17.1   for TFR treatment free survival
Vertical (Y-Axis) label “Prop. of pts. without treatment”>>


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Figure 14.2-17.3 Kaplan-Meier analysis of progression-free survival during the TFR phase, SDV sensitivity –
Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as Figure 14.2-17.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Figure 14.2-17.4 Kaplan-Meier analysis of treatment-free survival during the TFR phase, SDV sensitivity –
Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as Figure 14.2-17.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Figure 14.2-18.1 Kaplan-Meier analysis of reachievement of MMR, after loss of response in TFR –Subset of Full 
Analysis Set entering the re-treatment phase
<< Programming note: same shell as figure 14.2-4.1 for re-treatment
Months 0-36 for Arm 1, Months 0-24 for Arm 2
Vertical (Y-Axis) label “Prop. of pts. without re-achievement of MMR”>>
Figure 14.2-18.2 Kaplan-Meier analysis of reachievement of MR4.0, after loss of response in TFR – Subset of 
Full Analysis Set entering the re-treatment phase
<< Programming note: same shell as figure 14.2-4.1 for re-treatment
Months 0-36 for Arm 1, Months 0-24 for Arm 2>>
Vertical (Y-Axis) label “Prop. of pts. without re-achievement of MR4.0”


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Figure 14.2-18.3 Kaplan-Meier analysis of reachievement of MMR, after loss of response in TFR, SDV sensitivity
–Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as Figure 14.2-18.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Figure 14.2-18.4 Kaplan-Meier analysis of reachievement of MR4.0, after loss of response in TFR, SDV 
sensitivity – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as Figure 14.2-18.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Tables (Section 14.2)
Table 14.2-1.1 Description of BCR-ABL (IS) ratio at Month 3 and halving time of BCR-ABL (IS) ratio subgroups 
– Full Analysis Set
Subgroups                             
Arm 1
N=xxx
n (%)
Arm 2
N=xxx
n (%)
Randomized
N=xxx
n (%)
Not Randomized
N=xxx
n (%)
Total
N=xxx
n (%)
BCR-ABL (IS) ratio at Month 3-n (%)
n=xx  
n=xx  
n=xx  
n=xx  
n=xx  
  <= 0.005%
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  > 0.005%
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Halving time-n (%)
n=xx  
n=xx  
n=xx  
n=xx  
n=xx  
    <= 3 months (Day 91)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
    > 3 months (Day 91)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
- Percentage based on the number of patients with available data (n)


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Table 14.2-2.1.1 Molecular response MR4.0 at 12 months of TFR–Subset of Full Analysis Set entering the TFR 
phase
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Number of responders
xx
xx
xx
Percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Comparison Arm 1 vs Arm 2
p-value$ 
0.xxx
- Responders= Patients still in TFR with >=MR4.0, without molecular relapse.
- Confidence interval calculated as per Clopper-Pearson exact method.
- Percentage based on the number of patients included in the analysis population (N).
- Patients entered TFR considered for percentages denominator.
$ Pearson Chi-square test or Fisher’s exact test depending on the crosstabulation frequencies.
* p-value<0.05, ** p-value<0.01.
<<Programming note: 
-The percentage is obtained by dividing the number with response by number of patients entered TFR.>>
Comparison between Randomized and No Randomized group will be done for Demographics and baseline characteristics, History of 
prior Imatinib therapy, Cardiovascular risk factors, using: Pearson’s Chi-square test p-value, or Fisher’s exact test in case 
we have one or more frequencies in the cross-tabulation MR4.0 Yes/No*Randomized/Not Randomized, less than 5 for categorical 
variables, to check correlation between MR4.0 and Randomization group.
For numeric variables, Independent t-test for means (using “Equal” variances or “Unequal” variances depending on Variance test 
result) and Median test for median will be used to test for differences between Randomized and Not Randomized group. 
-Pearson’s Chi-square test p-value will be the first choice for categorical varaibles.
Fisher’s exact test will be used in case we have one or more frequencies in the cross-tabulation Variable*Randomized/Not 
Randomized, less than 5. >>
Table 14.2-2.1.2 Molecular response MR4.0 at 12 months of TFR–Subset of Per Protocol Analysis Set entering 
the TFR phase
<< Programming note: same shell as Table 14.2-2.1.1 for Per Protocol Set


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Table 14.2-2.1.3 Molecular response MR4.0 at 12 months of TFR–Full Analysis Set
<< Programming note: same shell as Table 14.2-2.1.1 for Full Analysis Set
Using the following footnotes:
Responders= Patients still in TFR with >=MR4.0, without molecular relapse.
- Confidence interval calculated as per Clopper-Pearson exact method.
- Percentage based on the number of patients included in the analysis population (N).
- FAS patients considered for percentages denominator.
- Patients randomized to Arm 1 and Arm 2 not entering the TFR phase will be considered as unsuccessful TFR. The same rule 
described in the previous section will be used to deal with any missing PCR assessment at Month 12.
$ Pearson Chi-square test or Fisher’s exact test depending on the crosstabulation frequencies.
* p-value<0.05, ** p-value<0.01.
Table 14.2-2.1.4 Molecular response MR4.0 at 12 months of TFR–Per Protocol Analysis Set
<< Programming note: same shell as Table 14.2-2.1.1 for Per Protocol Analysis Set
Using the following footnotes:
- Responders= Patients still in TFR with >=MR4.0, without molecular relapse.
- Confidence interval calculated as per Clopper-Pearson exact method.
- Percentage based on the number of patients included in the analysis population (N).
- PPS patients considered for percentages denominator.
- Patients randomized to Arm 1 and Arm 2 not entering the TFR phase will be considered as unsuccessful TFR. The same rule 
described in the previous section will be used to deal with any missing PCR assessment at Month 12.
$ Pearson Chi-square test or Fisher’s exact test depending on the crosstabulation frequencies.
* p-value<0.05, ** p-value<0.01.


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Table 14.2-2.1.5 Molecular response MR4.0 at 12 months of TFR– Subset of Full Analysis Set entering the TFR 
phase with MR4.0 achieved up to month 3 of pre-randomization Induction/Consolidation phase
<< Programming note: same shell as Table 14.2-2.1.1
Table 14.2-2.1.6 Molecular response MR4.0 at 12 months of TFR– Subset of Full Analysis Set entering the TFR 
phase with MR4.5 achieved up to month 3 of pre-randomization Induction/Consolidation phase
<< Programming note: same shell as Table 14.2-2.1.1
Table 14.2-2.1.7 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –Subset of Full Analysis Set 
entering the TFR phase
<< Programming note: Same shell as Table 14.2-2.1.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.2-2.1.8 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –Subset of Per Protocol 
Analysis Set entering the TFR phase
<< Programming note: Same shell as Table 14.2-2.1.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.2-2.1.9 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –Full Analysis Set
<< Programming note: Same shell as Table 14.2-2.1.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.2-2.1.10 Molecular response MR4.0 at 12 months of TFR, SDV sensitivity –Per Protocol Analysis Set
<< Programming note: Same shell as Table 14.2-2.1.4, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.2-2.2.1 Kaplan-Meier analysis of treatment-free survival during the TFR phase – Subset of Full 
Analysis Set entering the TFR phase
KM estimates
Arm 1
Arm 2
Number of patients – n(%)
with events
xx (xx.x)
xx (xx.x)
   Relapse
xx (xx.x)
xx (xx.x)
   Re-treatment with Nilotinib
xx (xx.x)
xx (xx.x)
   Progression to AP-BC
xx (xx.x)
xx (xx.x)
   Death from any cause
xx (xx.x)
xx (xx.x)
   Relapse + Death from any cause
xx (xx.x)
xx (xx.x)
   <<Note for programming:add any combination of events occurring on the same date>> 
with censorings
xx (xx.x)
xx (xx.x)
Time to event (months)
25th percentile (95% CI)
xx (xx.x, xx.x)
xx (xx.x xx.x))
Median (95% CI)
xx (xx.x xx.x))
xx (xx.x xx.x))
75th percentile (95% CI)
xx (xx.x xx.x))
xx (xx.x xx.x))
Percentage of patients without event –
Estimate  n(%)(95% CI) 
6 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
12 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
18 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
24 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
30 months
xx (xx.x)  (xx.x, xx.x)
36 months
xx (xx.x)  (xx.x, xx.x)
- NE: Not Estimable
- Patients randomized to Arm 2 have a maximum of 24 months of TFR phase. 
- Event = first occurrence of relapse, re-treatment with nilotinib, progression to AP/BC or death for any cause.
- Censoring rule = patients who did not meet the event are censored at the first date occurring between: the last contact 
date, the end of TFR phase and the date of death. 
- Time to event = (date of event – start date of TFR phase + 1)/30.4375. 
- n is the number of patients at risk at the timepoint (i.e. without event and still ongoing)
- The percentage of patients without event and the respective 95% C.I. are estimated from Kaplan Meier.


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Table 14.2-2.2.2 Kaplan-Meier analysis of treatment-free survival during the TFR phase – Subset of Per Protocol 
Analysis Set entering the TFR phase
<< Programming note: same shell as Table 14.2-2.2.1 for Per Protocol Set  
Table 14.2-2.2.3 Kaplan-Meier analysis of treatment-free survival during the TFR phase, SDV sensitivity –
Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as Table 14.2-2.2.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.2-2.2.4 Kaplan-Meier analysis of treatment-free survival during the TFR phase, SDV sensitivity –
Subset of Per Protocol Analysis Set entering the TFR phase
<< Programming note: Same shell as Table 14.2-2.2.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.2-2.3 Kaplan-Meier analysis of overall survival from Randomization–Randomized Set 
KM estimates
Arm 1
(N=xxx)
Arm 2
(N=xxx)
Number of patients – n(%)
with events (deaths)
xx (xx.x)
xx (xx.x)
with censorings
xx (xx.x)
xx (xx.x)
Time to event (months)
25th percentile (95% CI)
xx (xx.x, xx.x)
xx (xx.x xx.x))
Median (95% CI)
xx (xx.x xx.x))
xx (xx.x xx.x))
75th percentile (95% CI)
xx (xx.x xx.x))
xx (xx.x xx.x))
Percentage of patients without event –
Estimate  n(%)(95% CI) 
6 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
12 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
18 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
24 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
30 months
xx (xx.x)  (xx.x, xx.x)
36 months
xx (xx.x)  (xx.x, xx.x)
- NE: Not Estimable
Event = death for any cause.
- Censoring rule = patients who did not meet the event are censored at the first date occurring between: 
the last contact and the date of death. 
- Time to event = (date of event – Randomization date + 1)/30.4375. 
- n is the number of patients at risk at the timepoint (i.e. without event and still ongoing)
- The percentage of patients without event and the respective 95% C.I. are estimated from Kaplan Meier.


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Table 14.2-2.4 Kaplan-Meier analysis of progression-free survival during the TFR phase –- Subset of Full 
Analysis Set entering the TFR phase
KM estimates
Arm 1
Arm 2
Number of patients – n(%)
with events
xx (xx.x)
xx (xx.x)
with censorings
xx (xx.x)
xx (xx.x)
Time to event (months)
25th percentile (95% CI)
xx (xx.x, xx.x)
xx (xx.x xx.x))
Median (95% CI)
xx (xx.x xx.x))
xx (xx.x xx.x))
75th percentile (95% CI)
xx (xx.x xx.x))
xx (xx.x xx.x))
Percentage of patients without event –
Estimate n(%)(95% CI) 
6 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
12 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
18 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
24 months
xx (xx.x)  (xx.x, xx.x)
xx (xx.x)  (xx.x, xx.x)
30 months
xx (xx.x)  (xx.x, xx.x)
36 months
xx (xx.x)  (xx.x, xx.x)
- NE: Not Estimable
- Patients randomized to Arm 2 have a maximum of 24 months of TFR phase. 
- Event = first occurrence of progression to AP/BC or death for any cause.
- Censoring rule = patients who did not meet the event are censored at the first date occurring between: the last contact 
date, the end of TFR phase and the date of death. 
- Time to event = (date of event – start date of TFR phase + 1)/30.4375. 
- n is the number of patients at risk at the timepoint (i.e. without event and still ongoing)
- The percentage of patients without event and the respective 95% C.I. are estimated from Kaplan Meier.


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Table 14.2-2.5 Kaplan-Meier analysis of overall survival from Randomization, SDV sensitivity –Randomized Set 
<< Programming note: Same shell as Table 14.2-2.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.2-2.6 Kaplan-Meier analysis of progression-free survival during the TFR phase, SDV sensitivity –-
Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as Table 14.2-2.4, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.2-3.1 Major molecular response during pre-randomization Induction/Consolidation phase –Full 
Analysis Set
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Rate of major molecular response at 
Baseline 
Number of responders
xx
xx
xx
xx
xx
Response Rate % (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Rate of major molecular response at 
Month 3
Number of responders
xx
xx
xx
xx
xx
Response Rate % (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Rate of major molecular response at 
Month 6
...
...
...
...
...
...
Rate of major molecular response at 
Month 9
...
...
...
...
...
...
Rate of major molecular response at 
Month 12
...
...
...
...
...
...
Rate of major molecular response at 
Month 15
...
...
...
...
...
...
Rate of major molecular response at 
Month 18
...
...
...
...
...
...
Rate of major molecular response at 
Month 21
...
...
...
...
...
...
Rate of major molecular response at 
Month 24
...
...
...
...
...
...


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Rate of major molecular response at 
Month 24 (Nominal visit*)
...
...
...
...
...
...
- Rate was computed using time-window as described in the RAP Module 3.
- Percentage based on the number of patients included in the analysis population (N).
- Confidence interval calculated as per Clopper-Pearson exact method.
* Nominal visit is according to the CRF record, regardless of time-window derived visit.
<<Programming note: 
-The number of responders at Month x is obtained by counting all patients with a response on the last assessment of time-
window x.
-The percentage is obtained by dividing the number of responders by N.>>
Table 14.2-3.1.1 Major molecular response during pre-randomization Induction/Consolidation phase – LSC 
sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-3.1, for LSC sub-study FAS>>


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Table 14.2-3.2 Major molecular response during post-randomization consolidation phase (ARM 2)– Subset of 
Full Analysis Set randomized to Arm 2
Arm2
N=xx
Rate of major molecular response at Month 27
Number of responders
xx
Response Rate % (95% CI)
xx (xx.x, xx.x)
Rate of major molecular response at Month 27 (Nominal visit*)
Number of responders
xx
Response Rate % (95% CI)
xx (xx.x, xx.x)
Rate of major molecular response at Month 30
Number of responders
xx
Response Rate % (95% CI)
xx (xx.x, xx.x)
Rate of major molecular response at Month 33 
Number of responders
xx
...
...
Rate of major molecular response at Month 36
xx
...
...
Rate of major molecular response at Month 36 (Nominal vist*)
xx
...
...
- Rate was computed using time-window as described in the RAP Module 3.
- Percentage based on the number of patients included in the analysis population (N).
- Confidence interval calculated as per Clopper-Pearson exact method.
* Nominal visit is according to the CRF record, regardless of time-window derived visit.
Table 14.2-3.2.1 Major molecular response during post-randomization consolidation phase (ARM 2) – LSC sub-
study Full Analysis Set randomized to Arm 2 
<< Programming note: Same shell as table 14.2-3.2, for LSC sub-study FAS ARM 2>>


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Table 14.2-3.3 Major molecular response during TFR phase –Subset of Full Analysis Set patients entered TFR 
phase 
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Rate of major molecular response at Baseline 
Number of responders
xx
xx
xx
Response Rate % (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Rate of major molecular response at Month 3
Number of responders
xx
xx
xx
Response Rate % (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Rate of major molecular response at Month 6
...
...
...
...
Rate of major molecular response at Month 9
...
...
...
...
Rate of major molecular response at Month 12
...
...
...
...
Rate of major molecular response at Month 15
...
...
...
...
Rate of major molecular response at Month 18
...
...
...
...
Rate of major molecular response at Month 21
...
...
...
...
Rate of major molecular response at Month 24
...
...
...
...
Rate of major molecular response at Month 24 (Nominal visit*)
...
...
...
...
Rate of major molecular response at Month 27 
...
...
...
...


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Rate of major molecular response at Month 27 (Nominal visit*)
...
...
...
...
Rate of major molecular response at Month 30 
...
...
...
...
Rate of major molecular response at Month 33 
...
...
...
...
Rate of major molecular response at Month 36 
...
...
...
...
Rate of major molecular response at Month 36 (Nominal visit*)
...
...
...
...
- Rate was computed using time-window as described in the RAP Module 3.
- Percentage based on the number of patients included in the analysis population (N).
- Confidence interval calculated as per Clopper-Pearson exact method.
* Nominal visit is according to the CRF record, regardless of time-window derived visit.
<<Programming note: 
-The number of responders at Month x is obtained by counting all patients with a response on the last assessment of time-
window x.
-The percentage is obtained by dividing the number of responders by N.>>
Table 14.2-3.4 Major molecular response during re-treatment phase–Subset of Full Analysis Set patients 
entered re- treatment phase 
<< Programming note: Same shell as table 14.2-3.3, time-window: Day 1, Week 6, Month 3 up to Month 36 by 3 for re-treatment two 
arms>>


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Table 14.2-3.5 Major molecular response during TFR phase –Subset of Full Analysis Set patients entered TFR 
phase with MR4.0 achieved up to month 3 of pre-randomization Induction/Consolidation phase
<< Programming note: same shell as Table 14.2-3.3
Table 14.2-3.6 Major molecular response during TFR phase –Subset of Full Analysis Set patients entered TFR 
phase with MR4.5 achieved up to month 3 of pre-randomization Induction/Consolidation phase
<< Programming note: same shell as Table 14.2-3.3
Table 14.2-3.7 Major molecular response during TFR phase, SDV sensitivity –Subset of Full Analysis Set 
patients entered TFR phase 
<< Programming note: Same shell as Table 14.2-3.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.2-3.8 Major molecular response during re-treatment phase, SDV sensitivity –Subset of Full Analysis 
Set patients entered re- treatment phase 
<< Programming note: Same shell as Table 14.2-3.4, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.2-4.1 Molecular response 4.0 during pre-randomization Induction/Consolidation phase – Full Analysis 
Set
<< Programming note: Same shell as table 14.2-3.1, for MR4.0 >>
Table 14.2-4.1.1 Molecular response 4.0 during pre-randomization Induction/Consolidation phase – LSC sub-
study Full Analysis Set
<< Same shell as table 14.2-3.1, for LSC sub-study FAS MR4.0 ARM 2 >>
Table 14.2-4.2.1 Molecular response 4.0 during post-randomization consolidation phase (ARM 2) – Subset of 
Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-3.2, for MR4.0 ARM 2>>
Table 14.2-4.2.2 Molecular response 4.0 during post-randomization consolidation phase (ARM 2) – Subset of  
Per Protocol randomized to Arm 2
<< Programming note: Same shell as table 14.2-4.2.1, for PPS>>
Add footnote:
Per Protocol Analysis Set (PPS) comprises all subjects who are enrolled without major protocol deviation (PD severity codes: 
0, 1, 5, 8).
Table 14.2-4.2.11 Molecular response 4.0 during post-randomization consolidation phase (ARM 2) – Subset of  
LSC sub-study Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-3.1, for LSC sub-study FAS MR4.0 ARM 2>>


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Table 14.2-4.3.1 Molecular response 4.0 during TFR phase – Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.2-3.3, for MR4.0 TFR two arms >>
Table 14.2-4.3.2 Molecular response 4.0 during TFR phase – Subset of Per Protocol Analysis Set entering the 
TFR phase
<< Programming note: Same shell as table 14.2-4.3.1, for PPS>>
Add footnote:
Per Protocol Analysis Set (PPS) comprises all subjects who are enrolled without major protocol deviation (PD severity codes: 
0, 1, 5, 8).
Table 14.2-4.3.3 Molecular response 4.0 during TFR phase , SDV sensitivity – Subset of Full Analysis Set 
entering the TFR phase
<< Programming note: Same shell as Table 14.2-4.3.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.2-4.4 Molecular response 4.0 during re-treatment phase – Subset of Full Analysis Set entering the re-
treatment phase
<< Programming note: Same shell as table 14.2-3.4, for MR4.0 re-treatment two arms >>
Table 14.2-4.5 Molecular response 4.0 during TFR phase – Subset of Full Analysis Set entering the TFR phase 
with MR4.0 achieved up to month 3 of pre-randomization Induction/Consolidation phase
<< Programming note:: same shell as table 14.2-4.3.1 >>
Table 14.2-4.6 Molecular response 4.0 during TFR phase – Subset of Full Analysis Set entering the TFR phase 
with MR4.5 achieved up to month 3 of pre-randomization Induction/Consolidation phase
<< Programming note: same shell as table 14.2-4.3.1 >>
Table 14.2-4.7 Molecular response 4.0 during re-treatment phase, SDV sensitivity – Subset of Full Analysis 
Set entering the re-treatment phase
<< Programming note: Same shell as Table 14.2-4.4, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.2-5.1 Molecular response 4.5 during pre-randomization Induction/Consolidation– Full Analysis Set
<< Programming note: Same shell as table 14.2-3.1, for MR4.5, exclude Month 24 (Nominal visit*) >>
Table 14.2-5.1.1 Molecular response 4.5 during pre-randomization Induction/Consolidation– LSC sub-study 
Full Analysis Set
<< Programming note: Same shell as table 14.2-5.1, for LSC sub-study FAS MR4.5 >>
Table 14.2-5.2 Molecular response 4.5 during post-randomization consolidation phase (ARM 2) – Subset of Full 
Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-3.2, for MR4.5 ARM 2, exclude Month 27 (Nominal visit*) and Month 36 (Nominal 
vist*)>>
Table 14.2-5.2.1 Molecular response 4.5 during post-randomization consolidation phase (ARM 2) – Subset of 
LSC sub-study Full Analysis Set randomized to  Arm 2
<< Programming note: Same shell as table 14.2-5.1, for LSC sub-study FAS MR4.5 ARM 2>>
Table 14.2-5.3 Molecular response 4.5 during TFR phase – Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.2-3.3, for MR4.5 TFR two arms, exclude Month 24 (Nominal visit*), Month 27 (Nominal 
visit*), Month 36 (Nominal visit*) >>
Table 14.2-5.4 Molecular response 4.5 during re-treatment phase – Subset of Full Analysis Set entering the re-
treatment phase
<< Programming note: Same shell as table 14.2-3.4, for MR4.5 re-treatment two arms exclude Month 24 (Nominal visit*), Month 27 
(Nominal visit*), Month 36 (Nominal visit*) >>


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Table 14.2-5.5 Molecular response 4.5 during TFR phase – Subset of Full Analysis Set entering the TFR phase 
with MR4.0 achieved up to month 3 of pre-randomization Induction/Consolidation phase
<< Programming note: same shell as table 14.2-5.3 >>
Table 14.2-5.6 Molecular response 4.5 during TFR phase – Subset of Full Analysis Set entering the TFR phase 
with MR4.5 achieved up to month 3 of pre-randomization Induction/Consolidation phase
<< Programming note: same shell as table 14.2-5.3 >>
Table 14.2-5.7 Molecular response 4.5 during TFR phase, SDV sensitivity – Subset of Full Analysis Set entering 
the TFR phase
<< Programming note: Same shell as Table 14.2-5.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.2-5.8 Molecular response 4.5 during re-treatment phase, SDV sensitivity  – Subset of Full Analysis 
Set entering the re-treatment phase
<< Programming note: Same shell as Table 14.2-5.4, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.2-6.1 Raw cumulative incidence MMR during pre-randomization Induction/Consolidation phase – Full 
Analysis Set
Arm 1
Arm 2
Randomized
Not Randomized
Total
N=xx
N=xx
N=xx
N=xx
N=xx
Major molecular response at 
baseline 
Number of responders
xx
xx
xx
xx
xx
Percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Cumulative major molecular 
response up to 3 months (Day 91)
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Cumulative major molecular 
response up to 6 months (Day 
183)
Cumulative number of responders
xx
xx
xx
xx
xx
...
...
...
...
...
...
Cumulative major molecular 
response up to 9 months (Day 
274)
...
...
...
...
...
...
Cumulative major molecular 
response up to 12 months (Day 
365)
...
...
...
...
...
...
Cumulative major molecular 
response up to 15 months (Day 
457)
...
...
...
...
...
...
Cumulative major molecular 
response up to 18 months (Day 
548)


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...
...
...
...
...
...
Cumulative major molecular 
response up to2 21 months (Day 
639)
...
...
...
...
...
...
Cumulative Major molecular 
response up to 24 months (Day 
731)
- Percentage based on the number of patients in the analysis population (N).
- Confidence interval calculated as per Clopper-Pearson exact method.
<<Programming note: 
-Cumulative number with response at Month x is obtained by counting all patients with a time to response in days before Day 
x;-The percentage is obtained by dividing the number with response by N.>>
Table 14.2-6.1.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
– LSC sub-study Full Analysis Set  
<< Programming note: Same shell as table 14.2-6.1, for LSC sub-study FAS>>
Table 14.2-6.2 Raw cumulative incidence MMR during post-randomization Consolidation phase (ARM 2)  -
Subset of  Full Analysis Set patients randomized to ARM 2  
<< Programming note: Same shell as table 14.2-6.1, for ARM 2 only>>
Table 14.2-6.2.1 Raw cumulative incidence MMR during post-randomization Consolidation phase (ARM 2)  -
Subset of  LSC sub-study Fulls Anslysis Set randomized to ARM 2
<< Programming note: Same shell as table 14.2-6.1, for LSC sub-study FAS ARM 2 only>>


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Table 14.2-6.3 Raw cumulative incidence of MMR during re-treatment phase – Subset of Full Analysis Set 
entering the re-treatment phase
<< Programming note: Same shell as table 14.2-6.1, for re-treatment two arms >>
<<Programming note: From M27 onwards, arm2 patients should not be counted for the Total column>>
Use “Total*” for Total column and add footnote:
“* For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.” 
Table 14.2-6.4 Raw cumulative incidence of MMR during re-treatment phase , SDV sensitivity  – Subset of Full 
Analysis Set entering the re-treatment phase
<< Programming note: Same shell as Table 14.2-6.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.2-7.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation phase 
– Full Analysis Set  
<< Programming note: Same shell as table 14.2-6.1, for MR4.0>>
Table 14.2-7.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation 
phase – LSC sub-study Full Analysis Set  
<< Programming note: Same shell as table 14.2-6.1.1, for MR 4.0>>


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Table 14.2-7.2 Raw cumulative incidence of MR 4.0 during post-randomization consolidation phase (ARM 2) –
Subset of Full Analysis Set randomized to ARM 2  
< Programming note: < Same shell as table 14.2-6.2, for MR4.0 ARM 2 only>>
Table 14.2-7.2.1 Raw cumulative incidence of MR 4.0 during post-randomization consolidation phase (ARM 2) 
– Subset of LSC sub-study Full Analysis Set  randomized to ARM 2  
<< Programming note: Same shell as table 14.2-6.2.1, for MR4.0>>
Table 14.2-7.3 Raw cumulative incidence of MR 4.0 during re-treatment phase – Subset of Full Analysis Set 
entering the re-treatment phase
<< Programming note: Same shell as table 14.2-6.3, for MR 4.0 two arms >>
<<Programming note: From M27 onwards, arm2 patients should not be counted for the Total column>>
Use “Total*” for Total column and add footnote:
“* For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.” 
Table 14.2-7.4 Raw cumulative incidence of MR 4.0 during re-treatment phase, SDV sensitivity  – Subset of 
Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as Table 14.2-7.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.2-8.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation phase 
– Full Analysis Set
<< Programming note: Same shell as table 14.2-6.1, for MR4.5 >>
Table 14.2-8.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation 
phase – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-6.1, for MR 4.5>>
Table 14.2-8.2 Raw cumulative incidence of MR 4.5 during post-randomization consolidation phase (ARM 2) -
Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-6.2, for MR4.5 ARM 2 >>
Table 14.2-8.2.1 Raw cumulative incidence of MR 4.5 during post-randomization consolidation phase (ARM 2) 
- Subset of LSC sub-study Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-6.2.1, for MR 4.5 ARM 2>>
Table 14.2-8.3 Raw cumulative incidence of MR 4.5 during re-treatment phase - Subset of Full Analysis Set 
entering the re-treatment phase
<< Programming note: Same shell as table 14.2-6.3, for MR 4.5 two arms >>
<<Programming note: From M27 onwards, arm2 patients should not be counted for the Total column>>
Use “Total*” for Total column and add footnote:
“* For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.” 


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Table 14.2-8.4 Raw cumulative incidence of MR 4.5 during re-treatment phase , SDV sensitivity - Subset of Full 
Analysis Set entering the re-treatment phase
<< Programming note: Same shell as Table 14.2-8.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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By halving time of BCR-ABL (IS) ratio
Table 14.2-9.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation 
phase by halving time of BCR-ABL (IS) ratio – Full Analysis Set  
Halving time <= 3 months  /
Halving time > 3 months
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
All patients
N=xx
Major molecular response at baseline 
Number of responders
xx
xx
xx
xx
xx
Percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Cumulative major molecular response 
up to 3 months (Day 91)
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Repeat for all time-points
...
Cumulative major molecular response 
up to 24 months (Day 730)
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
- Percentage based on the number of patients included in the analysis population (N)
- Confidence Interval calculated as per Clopper-Pearson exact method
<<Programming note: 
-Refer to the programming note of table 14.2-6.1.>>
Table 14.2-9.1.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
by halving time of BCR-ABL (IS) ratio – LSC sub-study Full Analysis Set  
<< Programming note: Same shell as table 14.2-9.1, for LSC sub-study FAS>>


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Table 14.2-9.2 Raw cumulative incidence of MMR during post-randomization consolidation phase (ARM 2) by 
halving time of BCR-ABL (IS) ratio - Subset of Full Analysis Set randomized to Arm 2
Halving time <= 3 months  /
Halving time > 3 months
Arm 2
N=xx
Molecular response 4.0 at baseline
Number of responders
xx
Percentage (95% CI)
xx (xx.x, xx.x)
Cumulative molecular response 4.0 up 
to 27 months (Day 822)
Cumulative number of responders
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
Cumulative molecular response 4.0 up 
to 30 months (Day 913)
...
...
Repeat until 36 months
Cumulative molecular response 4.0 up 
to 36 months (Day 1096)  
Cumulative number of responders
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
- Percentage based on the number of patients included in the analysis population (N)
- Confidence Interval calculated as per Clopper-Pearson exact method
<< Programming note: Same shell as table 14.2-9.1, for ARM 2 only


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Table 14.2-9.2.1 Raw cumulative incidence of MMR during post-randomization consolidation phase (ARM 2) 
by halving time of BCR-ABL (IS) ratio - Subset of LSC sub-study Full Analysis Set randomized to Arm 
2
<< Programming note: Same shell as table 14.2-9.2, for LSC sub-study FAS>>
Table 14.2-9.3 Raw cumulative incidence of MMR during re-treatment phase by halving time of BCR-ABL (IS) 
ratio – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.2-9.1, for Re-treatment two arms >>
<<Programming note: From M27 onwards, arm2 patients should not be counted for the Total column>>
Use “Total*” for Total column and add footnote:
“* For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.” 


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Table 14.2-10.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation phase 
by halving time of BCR-ABL (IS) ratio – Full Analysis Set
<< Programming note: Same shell as table 14.2-9.1, for MR 4.0 >>
Table 14.2-.10.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation 
phase by halving time of BCR-ABL (IS) ratio – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-9.1.1, for MR 4.0 >>
Table 14.2-10.2 Raw cumulative incidence of MR 4.0 during post-randomization consolidation phase (ARM 2) 
by halving time of BCR-ABL (IS) ratio - Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-9.2, for MR 4.0 ARM 2>>
Table 14.2-10.2.1 Raw cumulative incidence of MR 4.0 during post-randomization consolidation phase (ARM 
2) by halving time of BCR-ABL (IS) ratio - Subset of LSC sub-study Full Analysis Set randomized to 
Arm 2
<< Programming note: Same shell as table 14.2-9.2.1, for MR 4.0 ARM 2>>
Table 14.2-10.3 Raw cumulative incidence of MR4.0 during re-treatment phase by halving time of BCR-ABL 
(IS) ratio – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.2-9.3, for MR4.0 two arms >>
<<Programming note: From M27 onwards, arm2 patients should not be counted for the Total column>>
Use “Total*” for Total column and add footnote:


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“* For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.” 
Table 14.2-11.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation phase 
by halving time of BCR-ABL (IS) ratio – Full Analysis Set
<< Programming note: Same shell as table 14.2-9.1, for MR 4.5 >>
Table 14.2-.11.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation 
phase by halving time of BCR-ABL (IS) ratio – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-9.1.1, for MR 4.5 >>
Table 14.2-11.2 Raw cumulative incidence of MR 4.5 during post-randomization consolidation phase (ARM 2) 
by halving time of BCR-ABL (IS) ratio - Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-9.2, for MR 4.5 ARM 2>>
Table14.2-11.2.1 Raw cumulative incidence of MR 4.5 during post-randomization consolidation phase (ARM 2) 
by halving time of BCR-ABL (IS) ratio - Subset of LSC sub-study Full Analysis Set randomized to Arm 
2
<< Programming note: Same shell as table 14.2-9.2.1, for MR 4.5 ARM 2>>
Table 14.2-11.3 Raw cumulative incidence of MR4.5 during re-treatment phase by halving time of BCR-ABL 
(IS) ratio – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.2-9.3, for MR4.5 two arms >>
<<Programming note: From M27 onwards, arm2 patients should not be counted for the Total column>>


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Use “Total*” for Total column and add footnote:
“* For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.” 
By  BCR-ABL (IS) ratio at Month 3
Table 14.2-12.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
by BCR-ABL (IS) ratio at Month 3 – Full Analysis Set
<<Programming note: 
<< Same shell as table 14.2-9.1, 
with the following subgroups:
BCR-ABL (IS) at Month 3 <= 0.005
BCR-ABL (IS) at Month 3 > 0.005>>
Table 14.2-12.1.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
by BCR-ABL (IS) ratio at Month 3 – LSC sub-study Full Analysis Set
<<Programming note: 
<< Same shell as table 14.2-9.1.1, 
with the following subgroups:
BCR-ABL (IS) at Month 3 <= 0.005
BCR-ABL (IS) at Month 3 > 0.005>>
Table 14.2-12.2 Raw cumulative incidence of MMR during post-randomization consolidation phase (ARM 2) 
by BCR-ABL (IS) ratio at Month 3 - Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-9.2, 
with the following subgroups:
BCR-ABL (IS) at Month 3 <= 0.005
BCR-ABL (IS) at Month 3 > 0.005>>


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Table 14.2-12.2.1 Raw cumulative incidence of MMR during post-randomization consolidation phase (ARM 2) 
by BCR-ABL (IS) ratio at Month 3 - Subset of LSC sub-study Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-9.2.1, 
with the following subgroups:
BCR-ABL (IS) at Month 3 <= 0.005
BCR-ABL (IS) at Month 3 > 0.005>>
Table 14.2-12.3 Raw cumulative incidence of MMR during re-treatment phase by BCR-ABL (IS) ratio at Month 3 
– Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.2-9.2.3, 
with the following subgroups:
BCR-ABL (IS) at Month 3 <= 0.005
BCR-ABL (IS) at Month 3 > 0.005>>
<<Programming note: From M27 onwards, arm2 patients should not be counted for the Total column>>
Use “Total*” for Total column and add footnote:
“* For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.” 


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Table 14.2-13.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation phase 
by BCR-ABL (IS) ratio at Month 3 – Full Analysis Set
<< Programming note: Same shell as table 14.2-12.1, for MR4.0 >>
Table 14.2-13.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation 
phase by BCR-ABL (IS) ratio at Month 3 – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-12.1.1, for MR4.0 >>
Table 14.2-13.2 Raw cumulative incidence of MR 4.0 during post-randomization consolidation phase (ARM 2) 
by BCR-ABL (IS) ratio at Month 3 - Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-12.2, for MR4.0 >>
Table 14.2-13.2.1 Raw cumulative incidence of MR 4.0 during post-randomization consolidation phase (ARM 
2) by BCR-ABL (IS) ratio at Month 3 - Subset of LSC sub-study Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-12.2.1, for MR4.0 >>
Table 14.2-13.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by BCR-ABL (IS) ratio at Month 
3 – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.2-12.3, for MR4.0 >>
<<Programming note: From M27 onwards, arm2 patients should not be counted for the Total column>>
Use “Total*” for Total column and add footnote:
“* For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.” 


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Table 14.2-14.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation phase 
by BCR-ABL (IS) ratio at Month 3 – Full Analysis Set
<< Programming note: Same shell as table 14.2-12.1, for MR4.5 >>
Table 14.2-14.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation 
phase by BCR-ABL (IS) ratio at Month 3 – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-12.1.1, for MR4.5 >>
Table 14.2-14.2 Raw cumulative incidence of MR 4.5 during post-randomization consolidation phase (ARM 2) 
by BCR-ABL (IS) ratio at Month 3 - Subset of Full Analysis Set randomized to Arm 2
Programming note:
Table 14.2-14.2.1 Raw cumulative incidence of MR 4.5 during post-randomization consolidation phase (ARM 
2) by BCR-ABL (IS) ratio at Month 3 - Subset of LSC sub-study Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-12.2.1, for MR4.5 >>
Table 14.2-14.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by BCR-ABL (IS) ratio at Month 
3 – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.2-12.3, for MR4.5 >>
<<Programming note: From M27 onwards, arm2 patients should not be counted for the Total column>>
Use “Total*” for Total column and add footnote:
“* For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.” 


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By Sokal Risk category
Table 14.2-15.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation 
phase by Sokal Risk category– Full Analysis Set  
Low risk (<0.8)
Inermediate risk (>=0.8 - <=1.2)  
High risk (>1.2)
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
All patients
N=xx
Major molecular response at baseline 
Number of responders
xx
xx
xx
xx
xx
Percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Cumulative major molecular response 
up to 3 months (Day 91)
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Repeat for all time-points
...
Cumulative major molecular response 
up to 24 months (Day 730)
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
- Percentage based on the number of patients included in the analysis population (N)
- Confidence Interval calculated as per Clopper-Pearson exact method
Table 14.2-15.2 Raw cumulative incidence of MR4.0 during pre-randomization Induction/Consolidation phase 
by Sokal Risk category– Full Analysis Set  
<< Programming note: Same shell as table 14.2-15.1, for MR4.0>>


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Table 14.2-15.3 Raw cumulative incidence of MR4.5 during pre-randomization Induction/Consolidation phase 
by Sokal Risk category– Full Analysis Set  
<< Programming note: Same shell as table 14.2-15.1, for MR4.5>>


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By Time since initial diagnosis of CML
Table 14.2-16.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation 
phase by time since initial diagnosis of CML– Full Analysis Set  
<2 years
2 to 4 years
4 to 6 years
6 to 8 years
8 to 10 years
10 to 12 years
>= 12 years 
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
All patients
N=xx
Major molecular response at baseline 
Number of responders
xx
xx
xx
xx
xx
Percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Cumulative major molecular response 
up to 3 months (Day 91)
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Repeat for all time-points
...
Cumulative major molecular response 
up to 24 months (Day 730)
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
- Percentage based on the number of patients included in the analysis population (N)
- Confidence Interval calculated as per Clopper-Pearson exact method.


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Table 14.2-16.2 Raw cumulative incidence of MR4.0 during pre-randomization Induction/Consolidation phase 
by time since initial diagnosis of CML – Full Analysis Set  
<< Programming note: Same shell as table 14.2-16.1, for MR4.0>>
Table 14.2-16.3 Raw cumulative incidence of MR4.5 during pre-randomization Induction/Consolidation phase 
by time since initial diagnosis of CML – Full Analysis Set  
<< Programming note: Same shell as table 14.2-16.1, for MR4.5>>


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Suboptimal response
Table 14.2-17.1 Suboptimal response up to 24 months of pre-randomization Induction/Consolidation phase -  
Full Analysis Set patients who prematurely discontinued the pre-randomization 
Induction/Consolidation phase
        
Criteria
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
At least one criterion of suboptimal response 
n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
loss of CHR - n (%)          
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
loss of CCyR - n (%)         
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
loss of MMR - n (%)          
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
no MMR up to Month 24 - n (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
- Percentage based on the number of patients included in the analysis population (N).
- CHR: Complete hematologic response = normalization of hematopoiesis.
- CCyR: Complete cytogenetic response.                                                                                            
- Patient #
randomized to Arm 1 at 
 and discontinued Ind/cons at the same day for 
 
<<Programming note: 
- The loss of CHR, CCyR and MMR should be displayed only if they occurred before or at Month 24 (ie 730 days).
- no MMR up to Month 24 means no MMR up to 730 days.>>


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Table 14.2-17.2 Suboptimal response up to 12 months of post-randomization Consolidation phase (ARM 2)  -
Subset of  Full Analysis Set patients who prematurely discontinued the Induction/Consolidation 
phase randomized to Arm 2
Criteria
N=xx
At least one criterion of suboptimal response n (%)
xx (xx.x)
loss of CHR - n (%)          
xx (xx.x)
loss of CCyR - n (%)         
xx (xx.x)
loss of MMR - n (%)          
xx (xx.x)
no MMR up to Month 12*  - n (%)
xx (xx.x)
- Percentage based on the number of patients included in the analysis population (N).
- CHR: Complete hematologic response = normalization of hematopoiesis.
- CCyR: Complete cytogenetic response.
* After Randomization.
- 15 patients from ARM 2 discontinued during post-Randomization Consolidation phase.
                                                                         
<<Programming note: 
- The loss of CHR, CCyR and MMR should be displayed only if they occurred before or at Month 12  (ie 365  days) 12 months 
after randomization.
- no MMR up to Month 12   means no MMR up to 365 days (12 months after randomization).
Table 14.2-18.1 Suboptimal response up to 24 months of pre-randomization Induction/Consolidation phase -
Full Analysis Set
<<Programming note: 
- Same as Table 14.2-17.1 on all treated patients.>>
Table 14.2-18.2 Suboptimal response up to 12 months of post-randomization Consolidation phase - Subset of 
Full Analysis Set, randomized to ARM 2   
<<Programming note: 
- Same as Table 14.2-17.2 on all treated patients.>>


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Kinetics
Table 14.2-19.1 Kinetics of BCR-ABL (IS) ratio during pre-randomization Induction/Consolidation phase – Full 
Analysis Set
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
BCR-ABL (IS) (%) at Baseline
n
xx
xx
xx
xx
xx
Mean
xx.x
xx.x
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Min-Max
xx.x–xx.x
xx.x–xx.x
xx.x–xx.x
xx.x–xx.x
xx.x–xx.x
BCR-ABL (IS) (%) at Month 3
n
xx
xx
xx
xx
xx
..
Min-Max
xx.x–xx.x
xx.x–xx.x
xx.x–xx.x
xx.x–xx.x
xx.x–xx.x
Repeat at each time-point… 
BCR-ABL (IS) (%) at Month 36
n
xx
xx
xx
xx
xx
..
75th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Min-Max
xx.x–xx.x
xx.x–xx.x
xx.x–xx.x
xx.x–xx.x
xx.x–xx.x
         - The last value of BCR-ABL (IS) ratio per time-window is displayed in this table.  
Table 14.2-19.1.1 Kinetics of BCR-ABL (IS) ratio during pre-randomization Induction/Consolidation phase –
LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-19.1, for LSC sub-study FAS>>


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Table 14.2-19.2 Kinetics of BCR-ABL (IS) ratio during post-randomization consolidation phase (ARM 2) –
Subset of Full Analysis Set randomized to Arm 2
N=xx
BCR-ABL (IS) (%) at Month 27
n
xx
Mean
xx.x
SD
x.xx
25th Percentile
xx.x
Median
xx.x
75th Percentile
xx.x
Min Max
xx.x -xx.x
BCR-ABL (IS) (%) at Month 30
n
xx
...
…
Min Max
xx.x -xx.x
BCR-ABL (IS) (%) at Month 33
n               
xx
...
...
BCR-ABL (IS) (%) at Month 36
n
xx
...
...
Min Max
xx.x -xx.x
- The last value of BCR-ABL (IS) ratio per time-window is displayed in this table.  
Table 14.2-19.2.1 Kinetics of BCR-ABL (IS) ratio during post-randomization consolidation phase (ARM 2) –
Subset of LSC sub-study Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.2-19.2, for LSC sub-study FAS>>


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Table 14.2-19.3 Kinetics of BCR-ABL (IS) ratio during TFR phase – Subset of Full Analysis Set entering the TFR 
phase
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
BCR-ABL (IS) (%) at Month 1
n               
xx
xx
xx
Mean
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
Min-Max           
xx.x-xx.x
xx.x-xx.x
xx.x-xx.x
Repeat at each time-point every 1 month
BCR-ABL (IS) (%) at Month 6
n               
xx
xx
xx
...
...
...
...
Min-Max           
xx.x-xx.x
xx.x-xx.x
xx.x-xx.x
Repeat at each time-point every 2 months
BCR-ABL (IS) (%) at Month 12
n               
xx
Xx
xx
...
...
...
...
Min-Max           
xx.x-xx.x
xx.x-xx.x
xx.x-xx.x


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Repeat at each time-point every 3 months
BCR-ABL (IS) (%) at Month 24
n               
xx
Xx
xx
...
...
...
...
Min-Max           
xx.x-xx.x
xx.x-xx.x
xx.x-xx.x
Repeat at each time-point every 3 months
BCR-ABL (IS) (%) at Month 36
n               
xx
xx
...
...
...
Min-Max           
xx.x-xx.x
xx.x-xx.x
- Patients randomized to Arm 2 have a maximum of 24 months of TFR phase. 
- The last value of BCR-ABL (IS) ratio per time-window is displayed in this table.  


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Table 14.2-19.4 Kinetics of BCR-ABL (IS) ratio during re-treatment phase – Subset of Full Analysis Set entering 
the re-treatment phase
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
BCR-ABL (IS) (%) at Day 1
n               
xx
Xx
xx
Mean
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
Min-Max           
xx.x-xx.x
xx.x-xx.x
xx.x-xx.x
BCR-ABL (IS) (%) at Week 6
n               
xx
Xx
xx
...
...
...
...
Min-Max           
xx.x-xx.x
xx.x-xx.x
xx.x-xx.x
BCR-ABL (IS) (%) at Month 3
n               
xx
Xx
xx
...
...
...
...
Min-Max           
xx.x-xx.x
xx.x-xx.x
xx.x-xx.x
Repeat at each time-point every 3 months
BCR-ABL (IS) (%) at Month 36
n               
xx
xx
...
...
...
Min-Max           
xx.x-xx.x
xx.x-xx.x
- Patients randomized to Arm 2 have a maximum of 24 months of re-treatment phase. 
- The last value of BCR-ABL (IS) ratio per time-window is displayed in this table


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Table 14.2-19.5 Kinetics of BCR-ABL (IS) ratio during TFR phase, SDV sensitivity  – Subset of Full Analysis 
Set entering the TFR phase
<< Programming note: Same shell as Table 14.2-19.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.2-19.6 Kinetics of BCR-ABL (IS) ratio during re-treatment phase , SDV sensitivity  – Subset of Full 
Analysis Set entering the re-treatment phase
<< Programming note Same shell as Table 14.2-19.4, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Protocol No CAMN107AIC0
Patients Not reaching MMR/ MR 4.0 / MR 4.5
Table 14.2-20.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase -
Full Analysis Set patients not reaching MMR at baseline
<<Programming note: 
-Same shell as cumulative incidence of MMR table (14.2-6.1) but performed on the subset of subjects not reaching MMR at 
baseline (i.e. time-to-first MMR not equal to 0).
-Remove "Major molecular response at baseline". 
Table 14.2-20.2 Raw cumulative incidence of MMR during post-randomization Consolidation phase (ARM 2) -
Subset of Full Analysis Set patients not reaching MMR at baseline, randomized to ARM 2  
<<Programming note: 
-Same shell as cumulative incidence of MMR table (table 14.2-6.2) but performed on the subset of subjects not reaching MMR at 
baseline (i.e. time-to-first MMR not equal to 0).
Table 14.2-21.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation phase 
- Full Analysis Set patients not reaching MR 4.0 at baseline
<<Programming note: 
-Same shell as cumulative incidence of MR 4.0 table (14.2-7.1) but performed on the subset of subjects not reaching 4.0 at 
baseline (i.e. time-to-first MR 4.0 not equal to 0).
-Remove "Molecular response 4.0 at baseline". >>
Table 14.2-21.2 Raw cumulative incidence of MR 4.0 during post-randomization Consolidation phase (ARM 2) 
- Subset of Full Analysis Set patients not reaching MR 4.0 at baseline, randomized to ARM 2  
<<Programming note: 
-Same shell as cumulative incidence of MR 4.0 table (table 14.2-8.2) but performed on the subset of subjects not reaching MR 
4.0 at baseline (i.e. time-to-first MR 4.0 not equal to 0).
Table 14.2-22.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation phase 
-   Full Analysis Set patients not reaching MR 4.5 at baseline
<<Programming note: 
-Same shell as cumulative incidence of MR 4.5 table (table 14.2-9.1) but performed on the subset of subjects not reaching MR 
4.5 at baseline (i.e. time-to-first MR 4.5 not equal to 0).
-Remove "Molecular response 4.5 at baseline". >>


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Table 14.2-22.2 Raw cumulative incidence of MR 4.5 during post-randomization Consolidation phase (ARM 2)  
- Subset of  Full Analysis Set patients not reaching MR 4.5 at baseline, randomized to ARM 2  
<<Programming note: 
-Same shell as cumulative incidence of MR 4.5 table (table 14.2-9.2) but performed on the subset of subjects not reaching MR 
4.5 at baseline (i.e. time-to-first MR 4.5 not equal to 0).
-Refer to the programming note of table 14.2-6.2.>>
Table 14.2-22.3 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation phase 
- Full Analysis Set patients not reaching MMR at baseline
<<Programming note: 
-Same shell as cumulative incidence of MR 4.0 table (table 14.2-7.1) but performed on the subset of subjects not reaching MMR 
at baseline.>>
Table 14.2-22.4 Raw cumulative incidence of MR 4.0 during post-randomization Consolidation phase (ARM 2) 
- Subset of Full Analysis Set patients not reaching MMR at baseline, randomized to ARM 2  
<<Programming note: 
-Same shell as cumulative incidence of MR 4.0 table (table 14.2-7.2) but performed on the subset of subjects not reaching MMR 
at baseline.>>
Table 14.2-22.5 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation phase 
- Full Analysis Set patients not reaching MMR at baseline
<<Programming note: 
-Same shell as cumulative incidence of MR 4.5 table (table 14.2-8.1) but performed on the subset of subjects not reaching MMR 
at baseline.>>
Table 14.2-22.6 Raw cumulative incidence of MR 4.5 during post-randomization Consolidation phase (ARM 2) 
- Subset of Full Analysis Set patients not reaching MMR at baseline, randomized to ARM 2  
<<Programming note: 
-Same shell as cumulative incidence of MR 4.5 table (table 14.2-8.2) but performed on the subset of subjects not reaching MMR 
at baseline.>>


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Protocol No CAMN107AIC0
By BCR-ABL(IS) ratio at baseline
Table 14.2-23.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
by BCR-ABL(IS) ratio at baseline -  Full Analysis Set
BCR-ABL(IS) ratio >0.1% -  ≤1% /        
BCR-ABL(IS) ratio >0.01% -≤0.1%         
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Molecular response 4.0 at baseline
Number of responders
xx
xx
xx
xx
xx
Percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Cumulative molecular response 4.0 up 
to 3 months (Day 91)
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Cumulative molecular response 4.0 up 
to 6 months (Day 182)
...
...
...
...
...
...
Repeat until 24 months
Cumulative molecular response 4.0 up 
to 24 months (Day 730)  
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
- Percentage based on the number of patients included in the analysis population (N)
- Confidence Interval calculated as per Clopper-Pearson exact method
<<Programming note: 
-
Same shell as Table 4.8 but by BCR-ABL(IS) ratio (use MRCATBL = 2 for BCR-ABL(IS) ratio >0.1% - ≤1%, and MRCATBL = 3 
for BCR-ABL(IS) ratio >0.01% - ≤0.1%)>


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Table 14.2-23.1.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
by BCR-ABL (IS) ratio at baseline– LSC sub-study Full Analysis Set  
<< Programming note: Same shell as table 14.2-23.1, for LSC sub-study FAS>>
Table 14.2-23.2 Raw cumulative incidence of MMR during post-randomization consolidation phase (ARM 2) by 
BCR-BL(IS) ratio at baseline - Subset of  Full Analysis Set, randomized to ARM 2   
BCR-ABL(IS) ratio >0.1% -  ≤1% /        
BCR-ABL(IS) ratio >0.01% -≤0.1%         
N=xx
Molecular response 4.0 at baseline
Number of responders
xx
Percentage (95% CI)
xx (xx.x, xx.x)
Cumulative molecular response 4.0 up 
to 27 months (Day 822)
Cumulative number of responders
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
Cumulative molecular response 4.0 up 
to 30 months (Day 913)
...
...
Repeat until 36 months
Cumulative molecular response 4.0 up 
to 36 months (Day 1096)  
Cumulative number of responders
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
- Percentage based on the number of patients included in the analysis population (N)
- Confidence Interval calculated as per Clopper-Pearson exact method
<<Programming note: 


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-
Same shell as Table 4.8 but by BCR-ABL(IS) ratio (use MRCATBL = 2 for BCR-ABL(IS) ratio >0.1% - ≤1%, and MRCATBL = 3 
for BCR-ABL(IS) ratio >0.01% - ≤0.1%)>>
Table 14.2-23.2.1 Raw cumulative incidence of MMR during post-randomization consolidation phase (ARM 2)
by BCR-BL(IS) ratio at baseline - Subset of  LSC sub-study Full Analysis Set  , randomized to ARM 2   
<< Programming note: Same shell as table 14.2-23.2, for LSC sub-study FAS ARM 2>>
Table 14.2-23.3 Raw cumulative incidence of MMR during re-treatment phase by BCR-BL(IS) ratio at baseline 
– Subset of Full Analysis Set entering the re-treatment phase
<<Programming note: 
-
Same shell as Table 14.2-23.1, but for re-treatment two arms >>
Add footnote: *For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.”  Programing note 
added.”


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Table 14.2-24.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation phase 
by BCR-ABL(IS) ratio at baseline - Full Analysis Set
<< Programming note: Same shell as table 14.2-23.1, for MR 4.0 >>
Table 14.2-24.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation 
phase by BCR-ABL (IS) ratio at baseline– LSC sub-study Full Analysis Set  
<< Programming note: Same shell as table 14.2-23.1.1, for MR 4.0 >>
Table 14.2-24.2 Raw cumulative incidence of MR 4.0 during post-randomization consolidation phase (ARM 2)
by BCR-BL(IS) ratio at baseline - Subset of  Full Analysis Set, randomized to ARM 2   
<< Programming note: Same shell as table 14.2-24.2, for MR 4.0 >>
Table 14.2-24.2.1 Raw cumulative incidence of MR 4.0 during post-randomization consolidation phase (ARM 2)
by BCR-BL(IS) ratio at baseline - Subset of  LSC sub-study Full Analysis Set  , randomized to ARM 2   
<< Programming note: Same shell as table 14.2-24.2.1, for MR 4.0 >>
Table 14.2-24.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by BCR-BL(IS) ratio at 
baseline – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.2-24.3, for MR 4.0 >>
Add footnote: *For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.”  Programing note 
added.”


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Protocol No CAMN107AIC0
Table 14.2-25.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation phase 
by BCR-ABL(IS) ratio at baseline - Full Analysis Set
<< Programming note: Same shell as table 14.2-23.1, for MR 4.5 >>
Table 14.2-25.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation 
phase by BCR-ABL (IS) ratio at baseline– LSC sub-study Full Analysis Set  
<< Programming note: Same shell as table 14.2-23.1.1, for MR 4.5 >>
Table 14.2-25.2 Raw cumulative incidence of MR 4.5 during post-randomization consolidation phase (ARM 2)
by BCR-BL(IS) ratio at baseline - Subset of  Full Analysis Set, randomized to ARM 2   
<< Programming note: Same shell as table 14.2-24.2, for MR 4.5 >>
Table 14.2-25.2.1 Raw cumulative incidence of MR 4.5 during post-randomization consolidation phase (ARM 2)
by BCR-BL(IS) ratio at baseline - Subset of  LSC sub-study Full Analysis Set  , randomized to ARM 2   
<< Programming note: Same shell as table 14.2-24.2.1, for MR 4.5 >>
Table 14.2-25.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by BCR-BL(IS) ratio at 
baseline – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.2-24.3, for MR 4.5 >>
Add footnote: *For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.”  Programing note 
added.”


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Protocol No CAMN107AIC0
Loss of MMR/ MR 4.0, MR 4.5 during TFR
Table 14.2-26.1 Raw cumulative loss of MMR during TFR phase –Subset of Full Analysis Set entering the TFR 
phase
Arm 1
N=xx
Arm 2
N=xx
Total*
N=xx
Major molecular response at Baseline TFR
Number of responders
xx
xx
xx
Percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Cumulative loss of major molecular response up to 1 month (Day 30)
Cumulative number with loss
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Repeat at each-time point every month
Cumulative loss of major molecular response up to 6 months (Day 183)
Cumulative number with loss
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Repeat at each-time point every 2 months
Cumulative loss of major molecular response up to 12 months (Day 365)
Cumulative number with loss
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Repeat at each-time point every 3 months
Cumulative loss of major molecular response up to 36 months (Day 
1096)  
Cumulative number with loss
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
- The baseline TFR corresponds to the last available assessment before or on the last day of study drug intake from 
induction/consolidation phase.
- Patients randomized to Arm 2 have a maximum of 24 months of TFR phase.
- Confidence interval calculated as per Clopper-Pearson exact method.
- Percentage based on the number of patients included in the analysis population (N).
* For month 27 onwards, only Arm 1 patients considered for Total in percentages denominator.


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<<Programming note: 
-Cumulative number with response at Month x is obtained by counting all patients with a time to response in day before day x;
- Day x = round(30.4375*months).
-The percentage is obtained by dividing the number with response by N.>>
Table 14.2-26.2 Raw cumulative loss of MR4.0 during TFR phase –Subset of Full Analysis Set entering the 
TFR phase
<< Programming note: Same shell as table 14.2-26.1 replacing “major molecular response” by “molecular response 4.0”    >>
<<Programming note: From M27 onwards, Arm 2 patients should not be counted for the Total column>>
Table 14.2-26.3 Raw cumulative loss of MR4.5 during TFR phase –Subset of Full Analysis Set entering the 
TFR phase with MR4.5
<< Programming note: Same shell as table 14.2-26.1 replacing “major molecular response” by “molecular response 4.5” >>
<<Programming note: From M27 onwards, Arm 2 patients should not be counted for the Total column>>


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Protocol No CAMN107AIC0
Table 14.2-26.4 Raw cumulative loss of MMR during TFR phase, SDV sensitivity  –Subset of Full Analysis Set 
entering the TFR phase
<< Programming note: Same shell as Table 14.2-26.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.2-26.5 Raw cumulative loss of MR4.0 during TFR phase, SDV sensitivity –Subset of Full Analysis Set 
entering the TFR phase
<< Programming note: Same shell as Table 14.2-26.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.2-26.6 Raw cumulative loss of MR4.5 during TFR phase, SDV sensitivity –Subset of Full Analysis Set 
entering the TFR phase with MR4.5
<< Programming note: Same shell as Table 14.2-26.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Protocol No CAMN107AIC0
LSC substudy descriptives
Table 14.2-27.1 Descriptive Statistics for CD34 cells: Total percentage – LSC sub-study Full Analysis Set
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not 
Randomized
N=xx
Total
N=xx
Baseline [1]
       n
      Mean                                                 
      SD                                                   
      Min                                                  
      25th Percentile                                      
      Median                
      75th Percentile
      Max
xx
xx.x   
x.xx   
xx     
xx.x   
xx.x   
xx.x   
xx     
xx
xx.x   
x.xx   
xx     
xx.x   
xx.x   
xx.x   
xx     
xx
xx.x   
x.xx   
xx     
xx.x   
xx.x   
xx.x   
xx     
xx
xx.x   
x.xx   
xx     
xx.x   
xx.x   
xx.x   
xx     
xx
xx.x   
x.xx   
xx     
xx.x   
xx.x   
xx.x   
xx     
Month 24
       n
      ...
      Max
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
... 
xx     
Change from Baseline to Month 24
       n
      ...
      Max
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
... 
xx     
Month 36
...
...
...
...
...
Change from Baseline to Month 36
       n
      ...
      Max
-
...
-
xx
...   
xx     
xx
...   
xx     
xx
...   
xx     
xx
...   
xx     


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Protocol No CAMN107AIC0
EOP TFR
       n
      ...
      Max
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
... 
xx     
Change from Baseline to EOP TFR
       n
      ...
      Max
-
...
-
xx
...   
xx     
xx
...   
xx     
xx
...   
xx     
xx
...   
xx     
[1] Baseline is defined as latest visit between Screening or Rescreening.
- Change from Baseline derived if both baseline and timepoint evaluation are available.
- Only available numeric values are presented.


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Table 14.2-28.1 Descriptive Statistics for CD34+/CD38+ cells: Percentage from total CD34+ cells – LSC sub-
study Full Analysis Set
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not 
Randomized
N=xx
Total
N=xx
Comparison 
p-value#
Baseline [1]
       n
      Mean                                  
      SD                                    
      Min                                   
      25th Percentile                       
      Median                
      75th Percentile
      Max
xx
xx.x   
x.xx   
xx     
xx.x   
xx.x   
xx.x   
xx     
xx
xx.x   
x.xx   
xx     
xx.x   
xx.x   
xx.x   
xx     
xx
xx.x   
x.xx   
xx     
xx.x   
xx.x   
xx.x   
xx     
xx
xx.x   
x.xx   
xx     
xx.x   
xx.x   
xx.x   
xx     
xx
xx.x   
x.xx   
xx     
xx.x   
xx.x   
xx.x   
xx     
Month 24
       n
      ...
      Max
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
... 
xx     
Change from Baseline to Month 24
       n
      ...
      Max
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
... 
xx     
0.xxx
0.xxx
Month 36
...
...
...
...
...
Change from Baseline to Month 36
       n
      ...
      Max
-
...
-
xx
...   
xx     
xx
...   
xx     
xx
...   
xx     
EOP TFR
       n
      ...
      Max
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
... 
xx     


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Change from Baseline to EOP TFR
       n
      ...
      Max
xx
...
xx     
xx
...
xx     
xx
...
xx     
xx
... 
xx     
[1] Baseline is defined as latest visit between Screening or Rescreening.
- Change from Baseline derived if both baseline and timepoint evaluation are available.
- Only available numeric values are presented.
$ Comparison Rand. vs Not Rand. # P-value:independent t-test for means, Median test for medians.
* p-value<0.05, ** p-value<0.01.
Table 14.2-28.2 Descriptive Statistics for number of events sorted in CD34+/CD38+ cells – LSC sub-study Full 
Analysis Set
<< Programming note: Same shell as table 14.2-28.1 >>


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Table 14.2-28.3 Ph+ by HIS status, in CD34+/CD38+ cells – LSC sub-study Full Analysis Set  
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Baseline [1]
      Not Evaluable
      Negative
      Positive
      Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Month 24
      Not Evaluable
      Negative
      Positive
      Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Month 36
      Not Evaluable
      Negative
      Positive
      Missing
-
-
-
-
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
EOP TFR
      Not Evaluable
      Negative
      Positive
      Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
[1] Baseline is defined as latest visit between Screening or Rescreening.
Table 14.2-28.4 Descriptive statistics of Ph+ in CD34+/CD38+ cells– LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-28.1 >>
Table 14.2-28.5 BCR-ABL by RT-PCR status, in CD34+/CD38+ cells – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-28.3 >>


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Protocol No CAMN107AIC0
Repeat for CD34+/CD38- cells:
Table 14.2-29.1 Descriptive Statistics for CD34+/CD38- cells: Percentage from total CD34+ cells – LSC sub-
study Full Analysis Set
<< Programming note: Same shell as table 14.2-28.1, exclude p-values >>
Table 14.2-29.2 Descriptive Statistics for number of events sorted in CD34+/CD38- cells – LSC sub-study Full 
Analysis Set
<< Programming note: Same shell as table 14.2-28.1, exclude p-values >>
Table 14.2-29.3 Ph+ by HIS status, in CD34+/CD38- cells – LSC sub-study Full Analysis Set  
<< Programming note: Same shell as table 14.2-28.3 >>
Table 14.2-29.4 Descriptive statistics of Ph+ in CD34+/CD38- cells– LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-28.1, exclude p-values >>
Table 14.2-29.5 BCR-ABL by RT-PCR status, in CD34+/CD38- cells – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-28.3 >>


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Protocol No CAMN107AIC0
Repeat for Immunophenotypically aberrant CD34+ cells:
Table 14.2-30.1 Descriptive Statistics for Immunophenotypically aberrant CD34+ cells: Percentage from total 
CD34+ cells –LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-28.1, exclude p-values >>
Table 14.2-30.2 Descriptive Statistics for number of events sorted in Immunophenotypically aberrant CD34+ 
cells – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-28.1, exclude p-values >>
Table 14.2-30.3 Ph+ by HIS status, in Immunophenotypically aberrant CD34+ cells – LSC sub-study Full 
Analysis Set  
<< Programming note: Same shell as table 14.2-28.3 >>
Table 14.2-30.4 Descriptive statistics of Ph+ in Immunophenotypically aberrant CD34+ cells– LSC sub-study 
Full Analysis Set
<< Programming note: Same shell as table 14.2-28.1 >>
Table 14.2-30.5 BCR-ABL by RT-PCR status, in Immunophenotypically aberrant CD34+ cells – LSC sub-study 
Full Analysis Set
<< Programming note: Same shell as table 14.2-28.3 >>


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Repeat for Immunophenotypically aberrant CD34 negative cells:
Table 14.2-31.1 Descriptive Statistics for Immunophenotypically aberrant CD34- cells: Percentage from total 
CD34+ cells – LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-28.1 , exclude p-values >>
Table 14.2-31.2 Descriptive Statistics for number of events sorted in Immunophenotypically aberrant CD34-
cells- LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.2-28.1 , exclude p-values >>
Table 14.2-31.3 Ph+ by HIS status, in Immunophenotypically aberrant CD34- cells – LSC sub-study Full 
Analysis Set  
<< Programming note: Same shell as table 14.2-28.3 >>
Table 14.2-31.4 Descriptive statistics of Ph+ in Immunophenotypically aberrant CD34- cells– LSC sub-study 
Full Analysis Set
<< Programming note: Same shell as table 14.2-28.1 , exclude p-values >>
Table 14.2-31.5 BCR-ABL by RT-PCR status, in Immunophenotypically aberrant CD34- cells – LSC sub-study 
Full Analysis Set
<< Programming note: Same shell as table 14.2-28.3 >>


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By prior Imatinib treatment duration
Table 14.2-32.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
by duration of prior exposure to Imatinib -  Full Analysis Set
Duration of prior exposure to Imatinib (years) < 2 
Duration of prior exposure to Imatinib (years) >= 2 to <5 
Duration of prior exposure to Imatinib (years) >= 5 
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Molecular response 4.0 at baseline
Number of responders
xx
xx
xx
xx
xx
Percentage (95% CI)
xx (xx.x, 
xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Cumulative molecular response 4.0 up to 3 
months (Day 91)
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, 
xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Cumulative molecular response 4.0 up to 6 
months (Day 182)
...
...
...
...
...
...
Repeat until 24 months
Cumulative molecular response 4.0 up to 24 
months (Day 730)  
Cumulative number of responders
xx
xx
xx
xx
xx
Cumulative percentage (95% CI)
xx (xx.x, 
xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
- Percentage based on the number of patients included in the analysis population (N)
- Confidence Interval calculated as per Clopper-Pearson exact method.


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Table 14.2-32.1.1 Raw cumulative incidence of MMR during pre-randomization Induction/Consolidation phase 
by by prior Imatib treatment duration – LSC sub-study Full Analysis Set  
<< Programming note: Same shell as table 14.2-32.1, for LSC sub-study FAS>>
Table 14.2-32.2 Raw cumulative incidence of MMR during post-randomization consolidation phase (ARM 2) by 
prior Imatib treatment duration - Subset of  Full Analysis Set, randomized to ARM 2   
Duration of prior exposure (years) < 2 
Duration of prior exposure (years) >= 2 to <5 
Duration of prior exposure (years) >= 5 
Arm2
N=xx
Molecular response 4.0 at baseline
Number of responders
xx
Percentage (95% CI)
xx (xx.x, xx.x)
Cumulative molecular response 4.0 up to 27 months (Day 822)
Cumulative number of responders
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
Cumulative molecular response 4.0 up to 30 months (Day 913)
...
...
Repeat until 36 months
Cumulative molecular response 4.0 up to 36 months (Day 1096)  
Cumulative number of responders
xx
Cumulative percentage (95% CI)
xx (xx.x, xx.x)
- Percentage based on the number of patients included in the analysis population (N)
- Confidence Interval calculated as per Clopper-Pearson exact method


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Table 14.2-32.2.1 Raw cumulative incidence of MMR during post-randomization consolidation phase (ARM 2) 
by prior Imatib treatment duration - Subset of  LSC sub-study Full Analysis Set  , randomized to ARM 
2   
<< Programming note: Same shell as table 14.2-32.2, for LSC sub-study FAS ARM 2>>
Table 14.2-32.3 Raw cumulative incidence of MMR during re-treatment phase by prior Imatib treatment 
duration – Subset of Full Analysis Set entering the re-treatment phase
<<Programming note: 
-
Same shell as Table 14.2-32.1, but for re-treatment two arms >>
Add footnote: *For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.”  Programing note 
added.”


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Table 14.2-33.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation phase 
by prior Imatib treatment duration - Full Analysis Set 
<< Programming note: Same shell as table 14.2-32.1, for MR 4.0 >>
Table 14.2-33.1.1 Raw cumulative incidence of MR 4.0 during pre-randomization Induction/Consolidation 
phase by prior Imatib treatment duration – LSC sub-study Full Analysis Set  
<< Programming note: Same shell as table 14.2-32.1.1, for MR 4.0 >>
Table 14.2-33.2 Raw cumulative incidence of MR 4.0 during post-randomization consolidation phase (ARM 2)
by prior Imatib treatment duration - Subset of  Full Analysis Set, randomized to ARM 2   
<< Programming note: Same shell as table 14.2-32.2, for MR 4.0 >>
Table 14.2-33.2.1 Raw cumulative incidence of MR 4.0 during post-randomization consolidation phase (ARM 2)
by prior Imatib treatment duration - Subset of  LSC sub-study Full Analysis Set  , randomized to ARM 
2   
<< Programming note: Same shell as table 14.2-32.2.1, for MR 4.0 >>
Table 14.2-33.3 Raw cumulative incidence of MR 4.0 during re-treatment phase by prior Imatib treatment 
duration – Subset of Full Analysis Set entering the re-treatment phase 
<< Programming note: Same shell as table 14.2-32.3, for MR 4.0 >>
Add footnote: *For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.”  Programing note 
added.”


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Table 14.2-34.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation phase 
by prior Imatib treatment duration - Full Analysis Set 
<< Programming note: Same shell as table 14.2-32.1, for MR 4.5 >>
Table 14.2-34.1.1 Raw cumulative incidence of MR 4.5 during pre-randomization Induction/Consolidation 
phase by prior Imatib treatment duration – LSC sub-study Full Analysis Set  
<< Programming note: Same shell as table 14.2-32.1.1, for MR 4.5 >>
Table 14.2-34.2 Raw cumulative incidence of MR 4.5 during post-randomization consolidation phase (ARM 2)
by prior Imatib treatment duration - Subset of  Full Analysis Set, randomized to ARM 2   
<< Programming note: Same shell as table 14.2-32.2, for MR 4.5 >>
Table 14.2-34.2.1 Raw cumulative incidence of MR 4.5 during post-randomization consolidation phase (ARM 2)
by prior Imatib treatment duration - Subset of  LSC sub-study Full Analysis Set  , randomized to ARM 
2   
<< Programming note: Same shell as table 14.2-32.2.1, for MR 4.5 >>
Table 14.2-34.3 Raw cumulative incidence of MR 4.5 during re-treatment phase by prior Imatib treatment 
duration – Subset of Full Analysis Set entering the re-treatment phase 
<< Programming note: Same shell as table 14.2-32.3, for MR 4.5 >>
Add footnote: *For month 27 onwards, only Arm1 patients considered for Total in percentages denominator.”  Programing note 
added.”


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Protocol No CAMN107AIC0
Listings (Section 14.2)


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Section 14.3 – Safety data
Figures (Section 14.3)
Not applicable.
Tables (Section 14.3)
Table 14.3-1.1 Duration of exposure to study treatment during pre-randomization Induction/Consolidation– Safety Set 
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Exposure (months) - n (%)
< 6
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 6 - < 12
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 12 - < 18
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 18 - < =24
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
> 24
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Exposure (months)
n               
xx
Xx
Xx
Xx
xx
Mean
xx.x
xx.x
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Min-Max           
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
- Exposure (months) = (date of last administration – date of first administration in Induction/Consolidation phase + 
1)/30.4375.
- Safety Set consists of all patients who received at least one dose of study drug, excluding patients with PD severity codes 
(0, 5, 8).


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Table 14.3-1.1.1 Duration of exposure to study treatment during pre-randomization Induction/Consolidation– LSC sub-
study Safety Set
<< Programming note: Same shell as table 14.3-1.1, for LSC sub-study SAF >>
Table 14.3-1.2 Duration of exposure to study treatment during post-randomization Consolidation phase (ARM 
2) - Subset of Safety Set randomized to Arm 2
<< Programming note: Same shell as table 14.3-1.1.1 with arm 2 only. 
Use <6, >=6 to <=12 and >12 categories.
Footnote:
- Exposure (months) = (date of last administration – date of first administration in post-randomization consolidation phase + 
1)/30.4375.
- Safety Set consists of all patients who received at least one dose of study drug, excluding patients with PD severity codes 
(0, 5, 8).
Table 14.3-1.2.1 Duration of exposure to study treatment during post-randomization Consolidation phase (ARM 
2) - Subset of LSC sub-study Safety Set randomized to Arm 2
<< Programming note: Same shell as table 14.3-1.2, for LSC sub-study SAF >>


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Table 14.3-1.1.3 Duration of exposure to study treatment during re-treatment phase – Subset of Safety Set
entering the re-treatment phase
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Exposure (months) - n (%)
< 6
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 6 - < 12
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 12 - < 18
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 18 - < 24
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 24 - < 30
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 30 - < 36
xx (xx.x)
xx (xx.x)
>= 36
xx (xx.x)
xx (xx.x)
Exposure (months)
n               
xx
Xx
xx
Mean
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
Min-Max           
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
- Exposure (months) = (date of last administration – date of first administration in RT phase + 1)/30.4375.
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
- Safety Set consists of all patients who received at least one dose of study drug, excluding patients with PD severity codes 
(0, 5, 8).
Table 14.3-1.1.21 Duration of exposure to study treatment during pre-randomization Induction/Consolidation 
phase, by stable MR4.0 at 24 months and halving time - Safety Set


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Halving time <= 3 months
Halving time >  3 months
Stable MR4.0 at Month 24
N=xx
Unstable MR4.0 at Month 24
N=xx
Total
N=xx
Randomized
N=xx 
Not
Randomized
N=xx
Randomized
N=xx 
Not
Randomized
N=xx
Randomized
N=xx 
Not
Randomized
N=xx
Exposure (months) 
- n (%)
< 6
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
>= 6 - < 12
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
>= 12 - < 18
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
>= 18 - <= 24
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
> 24
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
Exposure (months)
n
xx
xx
xx
xx
xx
xx
Mean
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Min-Max
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
- Exposure (months) = (date of last administration – date of first administration in Induction/Consolidation phase + 
1)/30.4375.
- Safety Set consists of all patients who received at least one dose of study drug, excluding patients with PD severity codes 
(0, 5, 8).


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Table 14.3-1.1.22 Duration of exposure to study treatment during pre-randomization Induction/Consolidation 
phase, by stable MR4.0 by 24 months and halving time - Safety Set
Halving time <= 3 months
Halving time >  3 months
Stable MR4.0 by Month 24
N=xx
Unstable MR4.0 by Month 24
N=xx
Total
N=xx
Randomized
N=xx 
Not
Randomized
N=xx
Randomized
N=xx 
Not
Randomized
N=xx
Randomized
N=xx 
Not
Randomized
N=xx
Exposure (months) 
- n (%)
< 6
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
>= 6 - < 12
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
>= 12 - < 18
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
>= 18 - <= 24
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
> 24
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
xx(xx.x)
Exposure (months)
n
xx
xx
xx
xx
xx
xx
Mean
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
Min-Max
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
- Exposure (months) = (date of last administration – date of first administration in Induction/Consolidation phase + 
1)/30.4375.
- Safety Set consists of all patients who received at least one dose of study drug, excluding patients with PD severity codes 
(0, 5, 8).


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Table 14.3-2.1 Relative dose intensity and average daily dose during pre-randomization 
Induction/Consolidation phase – Safety Set
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Relative dose intensity -
n (%)
< 70%                     xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>=70 - <90%               xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>=90 - <100%
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>=100%
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Relative dose intensity
n               
xx
xx
xx
xx
xx
Mean
xx.x
xx.x
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Min-Max           
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
Average daily dose 
(mg/day)
n               
xx
xx
xx
xx
xx
Mean
xx.x
xx.x
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Min-Max           
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
- Actual dose intensity = Cumulative dose (mg) / Duration of exposure (day)
- Relative dose intensity = [Actual dose intensity /Planned dose intensity]*100
- Average daily dose = Cumulative dose (mg) / (date of end of medication – date of start of medication + 1) (day) 
where number of drug free days are included in the denominator.


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Table 14.3-2.1.1 Relative dose intensity and average daily dose during pre-randomization 
Induction/Consolidation phase – LSC sub-study Safety Set
<< Programming note: Same shell as table 14.3-2.1, for LSC sub-study SAF >>
Table 14.3-2.2 Relative dose intensity and average daily dose during post-randomization consolidation phase 
(ARM 2) – Subset of Safety Set randomized to Arm 2
<< Programming note: Same shell as table 14.3-1.2.1 with arm 2 only. 
Table 14.3-2.2.1 Relative dose intensity and average daily dose during post-randomization consolidation 
phase (ARM 2) – Subset of LSC sub-study Safety Set randomized to Arm 2
<< Programming note: Same shell as table 14.3-2.2, for LSC sub-study SAF ARM 2 only >>


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Table 14.3-2.3 Relative dose intensity and average daily dose during re-treatment phase – Subset of Safety 
Set entering the re-treatment phase
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Relative dose intensity - n (%)
< 70%                       
xx (xx.x)
xx (xx.x)
xx (xx.x)
>=70 - <90%                 
xx (xx.x)
xx (xx.x)
xx (xx.x)
>=90 - <100%
xx (xx.x)
xx (xx.x)
xx (xx.x)
>=100%
xx (xx.x)
xx (xx.x)
xx (xx.x)
Relative dose intensity
n               
xx
xx
xx
Mean
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
Min-Max           
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
Average daily dose (mg/day)
n               
xx
xx
xx
Mean
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
Min-Max           
xx.x- xx.x
xx.x- xx.x
xx.x- xx.x
- Actual dose intensity = Cumulative dose (mg) / Duration of exposure (day)
- Relative dose intensity = [Actual dose intensity /Planned dose intensity]*100
- Average daily dose = Cumulative dose (mg) / (date of end of medication – date of start of medication + 1) (day) where 
number of drug free days are included in the denominator


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Table 14.3-3.1 Dose reduction and interruption during pre-randomization Induction/Consolidation phase -
Safety Set
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Number of reductions / interruptions
0
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
2-3
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>=4
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients with at least one 
dose reduction/interruption by 
reason                        
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
                        
Adverse event
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Dosing error
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Lab test abnormality
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Scheduling conflict
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
- A patient with multiple occurrences of a reason for dose reduction or interruption is only counted once in that category.
- A patient with multiple reasons for dose reduction or interruption is only counted once in the total row. 
- Percentage based on the number of patients included in the analysis population (N).
Table 14.3-3.1.1 Dose reduction and interruption during pre-randomization Induction/Consolidation phase –
LSC sub-study Safety Set
<< Programming note: Same shell as table 14.3-3.1, for LSC sub-study SAF >>


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Table 14.3-3.2 Dose reduction and interruption during post-randomization consolidation phase (ARM 2) –
Subset of Safety Set randomized to Arm 2
<< Programming note: Same shell as table 14.3-1.3.1 with arm 2 only. 
Add following footnote as first:
- All medication starting at or after first study treatment exposure and before-randomization are reported in this table 
during the post-randomization consolidation phase.
Add footnote:
- 15 patients from ARM 2 discontinued during post-Randomization Consolidation phase.
Table 14.3-3.2.1 Dose reduction and interruption during post-randomization consolidation phase (ARM 2) –
Subset of LSC sub-study Safety Set randomized to Arm 2
<< Programming note: Same shell as table 14.3-3.2, for LSC sub-study SAF >>


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Table 14.3-3.3 Dose reduction and interruption during re-treatment phase – Subset of Safety Set entering the 
re-treatment phase
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Number of reductions / interruptions
0
xx (xx.x)
xx (xx.x)
xx (xx.x)
1
xx (xx.x)
xx (xx.x)
xx (xx.x)
2-3
xx (xx.x)
xx (xx.x)
xx (xx.x)
>=4
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of patients with at least one dose 
reduction/interruption by reason                
xx (xx.x)
xx (xx.x)
xx (xx.x)
Adverse event
xx (xx.x)
xx (xx.x)
xx (xx.x)
Dosing error
xx (xx.x)
xx (xx.x)
xx (xx.x)
Lab test abnormality
xx (xx.x)
xx (xx.x)
xx (xx.x)
Scheduling conflict
xx (xx.x)
xx (xx.x)
xx (xx.x)
Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
- A patient with multiple occurrences of a reason for dose reduction or interruption is only counted once in that category.
- A patient with multiple reasons for dose reduction or interruption is only counted once in the total row. 
- Percentage based on the number of patients included in the analysis population (N).


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Table 14.3-4.1 Concomitant medication by ATC class and preferred term during pre-randomization 
Induction/Consolidation phase Full Analysis Set
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not 
randomized
N=xx
Total
N=xx
Any ATC class
   -Total    
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ATC class 1
   -Total              
    Preferred term 1   
    Preferred term 2   
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ATC class 2
   -Total              
    Preferred term 1   
    Preferred term 2 
Etc.  
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
- All medication starting at or after enrollment and before randomization or DBL date or study completion/discontinuation are 
reported in this table.
- ATC classes are presented alphabetically; preferred terms are sorted within ATC class by frequency.
- A medication can appear with more than one ATC class.           
- A patient with multiple occurrences of a PT is counted only once in the PT class.       
- A patient with multiple PT within an ATC class is counted only once in the row describing the ATC class.
- Percentage based on the number of patients included in the analysis population (N).
Table 14.3-4.1.1 Concomitant medication by ATC class and preferred term during pre-randomization 
Induction/Consolidation phase LSC sub-study Full Analysis Set
<< Programming note: Same shell as table 14.3-4.1, for LSC sub-study FAS >>


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Table 14.3-4.2 Concomitant medication by ATC class and preferred term during post-randomization
consolidation phase (ARM 2)– Subset of Full Analysis Set randomized to Arm 2
N=xx
Any ATC class
   -Total    
xx (xx.x)
ATC class 1
   -Total              
    Preferred term 1   
    Preferred term 2   
xx (xx.x)
xx (xx.x)
xx (xx.x)
ATC class 2
   -Total              
    Preferred term 1   
    Preferred term 2 
Etc.  
xx (xx.x)
xx (xx.x)
xx (xx.x)
    
- All medication starting during the post-randomization consolidation phase. 
- ATC classes are presented alphabetically; preferred terms are sorted within ATC class by frequency.
- A medication can appear with more than one ATC class.           
- A patient with multiple occurrences of a PT is counted only once in the PT class.       
- A patient with multiple PT within an ATC class is counted only once in the row describing the ATC class.
- Percentage based on the number of patients included in the analysis population (N).
<< Programming notes:
All data from CMD must be taken after checking the start date is not before date of Visit 1. Note that an edit check is 
performed by Data Management to check that the starting date is not before Date of visit 1. 
Select DTAREP1C=1 (Is there any data to be reported? = yes) and CMDTYP1C=3   (Concomitant medication)
If ATC2 is missing and PT_TXT is not missing, then set “NON DRUG, THERAPIES and PROCEDURES” to ATC class
>>


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Table 14.3-4.2.1 Concomitant medication by ATC class and preferred term during post-randomization 
consolidation phase (ARM 2)– Subset of LSC sub-study Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3-2, for LSC sub-study FAS >>


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Table 14.3-4.3 Concomitant medication by ATC class and preferred term during TFR phase – Subset of Full 
Analysis Set entering the TFR phase
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Any ATC class
   -Total    
xx (xx.x)
xx (xx.x)
xx (xx.x)
ATC class 1
   -Total              
    Preferred term 1   
    Preferred term 2   
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ATC class 2
   -Total              
    Preferred term 1   
    Preferred term 2 
Etc.  
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
    - All medication starting at or after randomization and before the end of TFR phase or DBL date or study 
completion/discontinuation are reported in this table.
- ATC classes are presented alphabetically; preferred terms are sorted within ATC class by frequency.
- A medication can appear with more than one ATC class.           
- A patient with multiple occurrences of a PT is counted only once in the PT class.       
- A patient with multiple PT within an ATC class is counted only once in the row describing the ATC class.
- Patients randomized to Arm 1 have a maximum of 36 months of TFR phase; Patients randomized to Arm 2 have a maximum of 24 
months of TFR phase.
- Percentage based on the number of patients included in the analysis population (N).


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Table 14.3-4.4 Concomitant medication by ATC class and preferred term during re-treatment phase – Subset 
of Full Analysis Set entering the re-treatment phase
<<Programming note: Same shell as table 14.3-4 .3 but on re-treatment phase. Display the first following footnote: 
- All medication starting at or after start of re-treatment phase and before the DBL date or study completion/discontinuation
are reported in this table. 
- ATC classes are presented alphabetically; preferred terms are sorted within ATC class alphabetically.
- A medication can appear with more than one ATC class.           
- A patient with multiple occurrences of a PT is counted only once in the PT class.       
- A patient with multiple PT within an ATC class is counted only once in the row describing the ATC class.
-
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
- Percentage based on the number of patients included in the analysis population (N).
>>


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Table 14.3-5.1.1 Hematology shift table based on CTCAE grade during Pre-Randomization pre-randomization 
Induction/Consolidation –Full Analysis Set
                                                  Parameter: xxxxx
   
                      _Baseline Ind/Cons_  ______ Worst value during Pre-Randomization Ind/Cons treatment______
                                           Grade 0     Grade 1     Grade 2     Grade 3     Grade 4     Missing
Treatment                         n       n   (%)     n   (%)     n   (%)     n   (%)     n   (%)        n 
________________________________________________________________________________________________________________
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Arm 1                  Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                Grade 2    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                  etc.
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Arm 2                  Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                Grade 2    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                 etc.
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Grade 0    xx      xx (xx.x)  xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Randomized             Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                ...        ..      ...         ...         ...         ...          ...           ..
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Not Randomized         Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                ...        ..      ...         ...         ...         ...          ...           .. 
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Total                  Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                Grade 2    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                  etc.
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                                                                                                                           
- Baseline Ind/Cons corresponds to the last assessment before or on the first day of nilotinib intake during 
induction/consolidation phase.


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- Percentage calculated by row, based on number of available patients at Baseline Ind/Cons with corresponding grade and at 
least one non-missing post baseline value.
- Grades as per CTCAE v 4.03.
- Grade 0  = Non-missing value below Grade 1.
- Laboratory assessments performed outside of re-treatment phase are not described.
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
<<Programming note: 
- List of hematology parameters which have CTCAE grade in version 4.03 and have to be displayed: WBCs, absolute lymphocytes, 
absolute neutrophils, hemoglobin and platelets. 
- Note that the scheduled and unscheduled records are considered in this summary. 
- Do not display a line if all the records are 0 e.g. if there are no grade 4 at baseline the grade 4 line should not appear 
in the table. 
- % calculated by row excluding the patients with missing post baseline. 
- Note that a patient with Baseline only would be counted in the baseline count but would appear post baseline as missing and 
therefore would not be included in the denominator for the % calculation. >>


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Table 14.3-5.1.2 Hematology shift table based on CTCAE grade during post-randomization consolidation phase 
(ARM 2)– Subset of Full Analysis Set randomized to Arm 2
                                                  Parameter: xxxxx
   
                       ____ Baseline ___   ___________________ Worst on-treatment value____________________________________
                                           Grade 0     Grade 1     Grade 2     Grade 3     Grade 4     Missing
                                 n       n   (%)     n   (%)     n   (%)     n   (%)     n   (%)        n 
________________________________________________________________________________________________________________
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                 Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                Grade 2    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                  etc.
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx                                            
- Baseline is defined as the last assessment before or at the date the patient Randomized.
- Percentage calculated by row, based on number of available patients at Baseline with corresponding grade and at least one  
  non-missing post baseline value.
- Grades as per CTCAE v 4.03.
- Grade 0  = Non-missing value below Grade 1.
- Laboratory assessments performed outside of post-randomization consolidation phase are not described.
- Patients randomized to Arm 2 have 12 months of treatment post-randomization and a maximum of 24 months of re-treatment.
<<Programming note: 
- List of hematology parameters which have CTCAE grade in version 4.03 and have to be displayed: WBCs, absolute lymphocytes, 
absolute neutrophils, hemoglobin and platelets. 
- Note that the scheduled and unscheduled records are considered in this summary. 
- Do not display a line if all the records are 0 e.g. if there are no grade 4 at baseline the grade 4 line should not appear 
in the table. 
- % calculated by row excluding the patients with missing post baseline. 
- Note that a patient with Baseline only would be counted in the baseline count but would appear post baseline as missing and 
therefore would not be included in the denominator for the % calculation. >>


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Table 14.3-5.1.3 Hematology shift table based on CTCAE grade during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase
                                                  Parameter: xxxxx
   
                     __Baseline RT ___   _________________ Worst value during re-treatment_____________________
                                           Grade 0     Grade 1     Grade 2     Grade 3     Grade 4     Missing
Treatment                         n       n   (%)     n   (%)     n   (%)     n   (%)     n   (%)        n 
________________________________________________________________________________________________________________
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Arm 1                  Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                Grade 2    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                  etc.
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Arm 2                  Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                Grade 2    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                 etc.
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Total                  Grade 1    xx      xx (xx.x)  xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                Grade 2    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                  etc.
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                                                                                                                           
- Baseline RT corresponds to the last assessment before or at the date the patient entered re-treatment phase.
- Percentage calculated by row, based on number of available patients at Baseline RT with corresponding grade and at least       
one non-missing post baseline value.
- Grades as per CTCAE v 4.03.
- Grade 0  = Non-missing value below Grade 1.
- Laboratory assessments performed outside of re-treatment phase are not described.- Patients randomized to Arm 1 have 24 
months of treatment and a maximum of 36 months of re-treatment.
  Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.


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<<Programming note: 
- List of hematology parameters which have CTCAE grade in version 4.03 and have to be displayed: WBCs, absolute lymphocytes, 
absolute neutrophils, hemoglobin and platelets. 
- Note that the scheduled and unscheduled records are considered in this summary. 
- Do not display a line if all the records are 0 e.g. if there are no grade 4 at baseline the grade 4 line should not appear 
in the table. 
- % calculated by row excluding the patients with missing post baseline. 
- Note that a patient with Baseline only would be counted in the baseline count but would appear post baseline as missing and 
therefore would not be included in the denominator for the % calculation. >>


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Table 14.3-5.1.4 Hematology shift table based on CTCAE grade during whole study period – Full Analysis Set 
                                                  Parameter: xxxxx
   
                     __Baseline ___   _________________ Worst value during whole study period_____________________
                                           Grade 0     Grade 1     Grade 2     Grade 3     Grade 4     Missing
Treatment                         n       n   (%)     n   (%)     n   (%)     n   (%)     n   (%)        n 
________________________________________________________________________________________________________________
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Arm 1                  Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                Grade 2    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                  etc.
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Arm 2                  Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                Grade 2    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                 etc.
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Randomized             Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                ...        ..      ...         ...         ...         ...          ...           ..                   
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Not Randomized         Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                ...        ..      ...         ...         ...         ...          ...           ..
                  
                       Grade 0    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
Total                  Grade 1    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
(N=xxx)                Grade 2    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                  etc.
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)      xx 
                                                                                                                          
- Baseline is defined as the last available assessment before or at date of start of study treatment.
- Percentage calculated by row, based on number of available patients at Baseline with corresponding grade and at least one 
non-missing post baseline value.


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- Grades as per CTCAE v 4.03.
- Grade 0  = Non-missing value below Grade 1.
- Laboratory assessments performed outside of study period are not described.
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
<<Programming note: 
- List of hematology parameters which have CTCAE grade in version 4.03 and have to be displayed: WBCs, absolute lymphocytes, 
absolute neutrophils, hemoglobin and platelets. 
- Note that the scheduled and unscheduled records are considered in this summary. 
- Do not display a line if all the records are 0 e.g. if there are no grade 4 at baseline the grade 4 line should not appear 
in the table. 
- % calculated by row excluding the patients with missing post baseline. 
- Note that a patient with Baseline only would be counted in the baseline count but would appear post baseline as missing and 
therefore would not be included in the denominator for the % calculation. >>
Table 14.3-5.1.5 Hematology shift table based on CTCAE grade during re-treatment phase, SDV sensitivity   –
Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as Table 14.3-5.1.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.3-5.1.6 Hematology shift table based on CTCAE grade during whole study period , SDV sensitivity–
Full Analysis Set 
<< Programming note: Same shell as Table 14.3-5.1.4, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-5.2.1 Biochemistry shift table based on CTCAE grade during post-randomization consolidation 
phase (ARM 2)– Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3-5.1.2  >>
- List of biochemistry parameters which have CTCAE grade in version 4.03 and have to be displayed: bilirubin (total, indirect 
and direct), aspartate aminotransferase (AST), alanine aminotransferase (ALT), sodium (hyper & hypo), potassium (hyper & 
hypo), calcium (hyper & hypo), magnesium (hyper & hypo), glucose (hyper & hypo), creatinine, phosphate (or serum phosphorus), 
lipase, amylase, total cholesterol and triglycerides. 
- Note that for bi-directional parameters (where hyper and hypo abnormalities are defined), the value graded in the other 
direction (hyper if the parameter of interest is hypo) is counted as a grade 0. Note that the scheduled and unscheduled 
records are considered in this summary. Make sure the parameters to display can be changed, added and removed easily. >>
Table 14.3-5.2.2 Biochemistry shift table based on CTCAE grade during re-treatment phase– Subset of Full 
Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3-5.1.3 >>
Table 14.3-5.2.3 Biochemistry shift table based on CTCAE grade during whole study period – Full Analysis Set
<< Programming note: Same shell as table 14.3-5.1.4   >>
Table 14.3-5.2.4 Biochemistry shift table based on CTCAE grade during re-treatment phase, SDV sensitivity–
Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as Table 14.3-5.2.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.3-5.2.5 Biochemistry shift table based on CTCAE grade during whole study period, SDV sensitivity –
Full Analysis Set 
<< Programming note: Same shell as Table 14.3-5.2.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-6.1.1 Hematology shift table based on normal range for parameters with no defined CTCAE grades
during post-randomization consolidation phase (ARM 2)– Subset of Full Analysis Set randomized to 
Arm 2
                                                 Parameter: xxxxx                                                                       
                                                                                                              
                                             _ Worst value during post-randomization consolidation _
                             ___Baseline____    Low       Normal      High     High & Low  Missing
Treatment                              n      n   (%)    n   (%)    n   (%)    n   (%)     n 
________________________________________________________________________________________________
                       Low       xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
  (N=xxx)                    Normal    xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             High      xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Missing   xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Total     xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
-Baseline is defined as the last assessment before or at the date the patient Randomized.
- Percentage calculated by row, based on number of available patients at Baseline with corresponding level and at least one
  non-missing post baseline value. Low/High categories defined by normal ranges. 
- High & Low category defined when patients experienced low and high values (they are not count in Low category or High 
category). Only parameters without CTCAE grades are included.
- Laboratory assessments performed outside of the post-randomization consolidation phase are not described.
- Patients randomized to Arm 2 have 12 months of treatment post-randomization and a maximum of 24 months of re-treatment.
<<Programming note: List of Hematology parameters which do not have CTCAE grade in version 4.03 and have to be displayed: 
eosinophils, basophils, monocytes, promyelocytes, myelocytes, metamyelocytes and blast. 
Do not display a line if all the records are 0. 
% calculated by row excluding the patients with missing post baseline. 
Note that a patient with Baseline only would be counted in the baseline count but would appear post baseline as missing and 
therefore would not be included in the denominator for the % calculation.
>>


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Table 14.3-6.1.2 Hematology shift table based on normal range for parameters with no defined CTCAE grades 
during re-treatment phase – Subset of Full Analysis Set entering the re-treatment phase
                                                 Parameter: xxxxx                                                                      
                                                                                                              
                                             _________ Worst value during re-treatment __________
                          ___Baseline RT____    Low       Normal      High     High & Low  Missing
Treatment                              n      n   (%)    n   (%)    n   (%)    n   (%)     n 
________________________________________________________________________________________________
Arm 1                       Low       xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
  (N=xxx)                    Normal    xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             High      xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Missing   xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Total     xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
Arm 2                       Low       xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
  (N=xxx)                    Normal    xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             High      xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Missing   xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Total     xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
Total                       Low       xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
  (N=xxx)                    Normal    xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             High      xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Missing   xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Total     xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
- Baseline RT corresponds to the last assessment before or at the date the patient entered re-treatment phase. 
- Percentage calculated by row, based on number of available patients at Baseline RT with corresponding level
and at least one non-missing post baseline value. Low/High categories defined by normal ranges.  
- High & Low category defined when patients experienced low and high values (they are not count in
Low category or High category). Only parameters without CTCAE grades are included.                                                    
- Laboratory assessments performed outside of re-treatment phase are not described.
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.


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Table 14.3-6.1.3 Hematology shift table based on normal range for parameters with no defined CTCAE grades 
during whole study period –Full Analysis Set
                                                 Parameter: xxxxx                                                                       
                                                                                                              
                                             _______ Worst value during whole study period ________
                          ___Baseline____    Low       Normal      High     High & Low  Missing
Treatment                              n      n   (%)    n   (%)    n   (%)    n   (%)     n 
________________________________________________________________________________________________
Arm 1                       Low       xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
  (N=xxx)                    Normal    xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             High      xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Missing   xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Total     xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
Arm 2                       Low       xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
  (N=xxx)                    Normal    xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             High      xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Missing   xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Total     xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
Randomized                   Low       xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
  (N=xxx)                    Normal    xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             High      xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Missing   xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Total     xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
Not Randomized               Low       xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
  (N=xxx)                    Normal    xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             High      xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Missing   xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Total     xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
Total                       Low       xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
  (N=xxx)                    Normal    xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             High      xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Missing   xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    
                             Total     xx     xx (xx.x)  xx (xx.x)  xx (xx.x)  xx (xx.x)   xx    


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- Baseline is defined as the last available assessment before or at date of start of study treatment. 
- Percentage calculated by row, based on number of available patients at Baseline with corresponding level
and at least one non-missing post baseline value. Low/High categories defined by normal ranges.  
- High & Low category defined when patients experienced low and high values (they are not count in 
  Low category or High category). Only parameters without CTCAE grades are included.
- Laboratory assessments performed outside of study period are not described.
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
Table 14.3-6.1.4 Hematology shift table based on normal range for parameters with no defined CTCAE grades 
during re-treatment phase, SDV sensitivity – Subset of Full Analysis Set entering the re-treatment 
phase
<< Programming note: Same shell as Table 14.3-6.1.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.3-6.1.5 Hematology shift table based on normal range for parameters with no defined CTCAE grades 
during whole study period, SDV sensitivity –Full Analysis Set
<< Programming note: Same shell as Table 14.3-6.1.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-6.2.1 Biochemistry shift table based on normal range for parameters with no defined CTCAE grades 
during post-randomization consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to 
Arm 2
<< Programming note: Same shell as table 14.3-6.1.1  >>
Table 14.3-6.2.2 Biochemistry shift table based on normal range for parameters with no defined CTCAE grades 
during re-treatment phase – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3-6.1.2 >> 
Table 14.3-6.2.3 Biochemistry shift table based on normal range for parameters with no defined CTCAE grades 
during whole study period –Full Analysis Set 
<< Same shell as table 14.3-6.1.3 >>
Table 14.3-6.2.4 Biochemistry shift table based on normal range for parameters with no defined CTCAE grades 
during re-treatment phase, SDV sensitivity – Subset of Full Analysis Set entering the re-treatment 
phase
<< Programming note: Same shell as Table 14.3-6.2.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.3-6.2.5 Biochemistry shift table based on normal range for parameters with no defined CTCAE grades 
during whole study period, SDV sensitivity –Full Analysis Set
<< Programming note: Same shell as Table 14.3-6.2.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-7.1 ECG shift table based on notable values during Pre-randomization Induction Consolidation–Full 
Analysis Set 
                       Parameter: QTcF (msec)
                    __ Baseline Ind/Cons___  ______________Worst on-treatment value ______________
                                            <=450     >450 -480  >480 - 500     >500      Missing
Treatment                         n       n   (%)     n   (%)     n   (%)     n  (%)        n__ 
Arm 1                  <=450      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
  (N=xxx)              >450 - 480 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >480 - 500 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >500       xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
Arm 2                  <=450      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
  (N=xxx)              >450 - 480 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >480 - 500 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >500       xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
Randomized              <=450      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
  (N=xxx)             >450 - 480 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                    
...     ..      ...             ...        ...         ...          .. 
Not Randomized          <=450      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
  (N=xxx)              >450 - 480 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                    
...     ..      ...             ...        ...         ...          .. 
Total                 <=450      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
  (N=xxx)              >450 - 480 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                    
...     ..      ...             ...        ...         ...          .. 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
- Baseline Ind/Cons corresponds to the last assessment before or on the first day of nilotinib intake during 
induction/consolidation phase.
- Percentage for worst value is calculated by row, based on number of available patients at Baseline with corresponding 
category and at least one non-missing post baseline value.
- Unscheduled visits are included.
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.


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Table 14.3-7.2 ECG shift table based on notable values during post-randomization consolidation phase (ARM 
2) – Subset of Full Analysis Set randomized to Arm 2
                       Parameter: QTcF (msec)
                       ____ Baseline ___   ______________Worst on-treatment value ______________
                                            <=450     >450 -480  >480 - 500     >500      Missing
                                  n       n   (%)     n   (%)     n   (%)     n   (%)        n__ 
<=450      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
  (N=xxx)              >450 - 480 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >480 - 500 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >500       xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
- Baseline is defined as the last assessment before or at the date the patient Randomized.
- Percentage for worst value is calculated by row, based on number of available patients at Baseline with 
  corresponding category and at least one non-missing post baseline value.
- Unscheduled visits are included.
- Patients randomized to Arm 2 have 12 months of treatment post-randomization and a maximum of 24 months of re-treatment.
<<Programming note: Only patients with all missing values post-baseline will be counted in the ‘Missing’ column.>>


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Table 14.3-7.3 ECG shift table based on notable values during re-treatment phase – Subset of Full Analysis Set
entering the re-treatment phase
                       Parameter: QTcF (msec)
                    ___ Baseline RT ___   ______________Worst on-treatment value ______________
                                            <=450     >450 -480  >480 - 500     >500      Missing
Treatment                         n       n   (%)     n   (%)     n   (%)     n   (%)        n__ 
Arm 1                  <=450      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
  (N=xxx)              >450 - 480 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >480 - 500 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >500       xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
Arm 2                  <=450      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
  (N=xxx)              >450 - 480 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >480 - 500 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >500       xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                      Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
Total                 <=450      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
  (N=xxx)              >450 - 480 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >480 - 500 xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       >500       xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Missing    xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
                       Total      xx      xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)       xx 
- Baseline RT corresponds to the last assessment before or at the date the patient entered re-treatment phase. 
- Percentage for worst value is calculated by row, based on number of available patients at Baseline with corresponding 
category and at least one non-missing post baseline value.
- Unscheduled visits are included.
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
<<Programming note: Only patients with all missing values post-baseline will be counted in the ‘Missing’ column.>>


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Table 14.3-7.4 Notable ECG values during pre-randomization Ind/Cons –Full Analysis Set 
                                                  
                
            
Arm 1
N=xx
n (%)
Arm 2
N=xx
n (%)
Randomized
N=xx
n (%)
Not Randomized
N=xx
n (%)
Total
N=xx
n (%)
QTcF (msec)    
n=xx
n=xx
n=xx
n=xx
n=xx
  Increase from baseline Ind/Cons > 
30 
  Increase from baseline Ind/Cons > 
60
xx (xx.x) 
xx (xx.x)
xx (xx.x) 
xx (xx.x)
xx (xx.x) 
xx (xx.x)
xx (xx.x) 
xx (xx.x)
xx (xx.x) 
xx (xx.x)
- n is the number of patients meeting the criteria at least once. 
- Baseline Ind/Cons corresponds to the last assessment before or on the first day of nilotinib intake during 
induction/consolidation phase.
- Change from baseline: post baseline – baseline.
- Unscheduled visits are included.
- Percentage based on the number of patients with available data (n).
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
<<Programming note: Patients can be included in multiple rows.>>


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Table 14.3-7.5 Notable ECG values during post-randomization consolidation phase (ARM 2)– Subset of Full 
Analysis Set randomized to Arm 2
N=xx
n (%)
QTcF (msec)    
n=xx
  Increase from baseline > 30 
  Increase from baseline > 60
xx (xx.x) 
xx (xx.x)
                                                                                                          
- n is the number of patients meeting the criteria at least once. 
- Baseline is defined as the last assessment before or at the date the patient Randomized.
- Change from baseline: post baseline – baseline.
- Unscheduled visits are included.
- Percentage based on the number of patients with available data (n).
- Patients randomized to Arm 2 have 12 months of treatment post-randomization and a maximum of 24 months of re-treatment.
<<Programming note: Patients can be included in multiple rows.>>


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Table 14.3-7.6 Notable ECG values during re-treatment phase – Subset of Full Analysis Set entering the re-
treatment phase
                                                  
                
            
Arm 1
N=xx
n (%)
Arm 2
N=xx
n (%)
Total
N=xx
n (%)
QTcF (msec)    
n=xx
n=xx
n=xx
  Increase from baseline RT > 30 
  Increase from baseline RT > 60
xx (xx.x) 
xx (xx.x)
xx (xx.x) 
xx (xx.x)
xx (xx.x) 
xx (xx.x)
- n is the number of patients meeting the criteria at least once. 
- Baseline RT is defined as the last available assessment before or at date of re-start of study treatment.
- Change from baseline: post baseline – baseline.
- Unscheduled visits are included.
- Percentage based on the number of patients with available data (n).
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
<<Programming note: Patients can be included in multiple rows.>>
Table 14.3-7.7 ECG shift table based on notable values during re-treatment phase, SDV sensitivity – Subset of 
Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as Table 14.3-7.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.3-7.8 Notable ECG values during re-treatment phase, SDV sensitivity – Subset of Full Analysis Set 
entering the re-treatment phase
<< Programming note: Same shell as Table 14.3-7.6, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19


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Table 14.3-8.1 Echocardiography assessment at baseline – Full Analysis Set
Arm 1 
N=xxx
n (%)
Arm 2 
N=xxx
n (%)
Randomized
N=xxx
n (%)
Not Randomized
N=xxx
n (%)
Total
N=xxx
n (%)
LVEF (%)
n              
xx
xx
xx
xx
xx
Mean           
xx.x
xx.x
xx.x
xx.x
xx.x
SD             
x.xx
x.xx
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Median         
xx.x
xx.x
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Min-Max
xx.x – xx.x
xx.x – xx.x
xx.x – xx.x
xx.x – xx.x
xx.x – xx.x
Overall interpretation
n=xx
n=xx
n=xx
n=xx
n=xx
Normal                              
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Clinically insignificant abnormality
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Clinically significant abnormality  
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
- Percentage based on the number of patients with available data (n)


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Table 14.3-8.2 Echocardiography shift table based on overall interpretation - Full Analysis Set
                 ______Baseline __________             _______Worst post-baseline value _______________             
                                                                  Clinic insign.   Clinic. sign.        
                                                    Normal        abn.             abn.            Missing
Treatment                                n          n   (%)       n   (%)          n (%)             n
 
 
                _______
Arm 1            Normal                   xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
  (N=xxx)        Clinic. insign. abn.     xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
                 Clinic. sign. abn.       xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
                 Missing                  xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
                 Total                    xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
Arm 2            Normal                   xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
  (N=xxx)        Clinic. insign. abn.     xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
                 Clinic. sign. abn.       xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
                 Missing                  xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
                 Total                    xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
Randomized       Normal                   xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
  (N=xxx)        Clinic. insign. abn.     xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
...
  ...
...
  ...
...
  ...
Not Randomized  Normal                   xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
  (N=xxx)        Clinic. insign. abn.     xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
...
  ...
...
  ...
...
  ...
Total            Normal                   xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
  (N=xxx)        Clinic. insign. abn.     xx       xx (xx.x)       xx (xx.x)        xx (xx.x)         xx
...
  ...
...
  ...
...
  ...
- Baseline is defined as the last available assessment before or at date of start of study treatment
- Percentage for worst value is calculated by row, based on number of available patients at Baseline with corresponding 
category and at least one non-missing post baseline value (1-24 months for Arm 1, Not Randomized and Total, 1-36 months for 
Arm 2).
- Unscheduled visits are included
- Clinic. insign abn. = Clinically insignificant abnormality, Clinic. sign. abn. = Clinically significant abnormality
- According to the protocol the Echocardiography is performed at screening and may be repeated at the             
Investigator’s discretion if there are signs or symptoms of cardiotoxicity                                         


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Table 14.3-8.3 Echocardiography shift table based on overall interpretation, SDV sensitivity - Full Analysis Set
<< Programming note: Same shell as Table 14.3-8.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-9.1 Summary statistics of total cholesterol, HDL, LDL, glucose, microalbumin and HbA1c over 
Induction/Consolidation phase – Full Analysis Set
                                                                         
All patients /Arm 1/  Arm 2/ /Randomized/ Not Randomized
N=xx
______________________________________________________________________________________________________________
Test (unit)
Visit
n
Mean
SD
25th Perc.
Median
75th Perc.
Missing
______________________________________________________________________________________________________________
Total cholesterol (mmol/L)
Screening
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
Baseline visit   
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
VM1-Month 1   
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V1-Month 3
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V2-Month 6
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V3-Month 9   
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V4-Month 12   
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V5-Month 15
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V6-Month 18
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V7-Month 21
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V8-Month 24
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V400- EOP-ind/con
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V201-Month 27 *
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V202-Month 30 *
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V203-Month 33 *
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
V204-Month 36 *
xx
x.xx
x.xx
x.xx
x.xx
x.xx
xx
   
   -
Unscheduled visits are taken into account. For each visit, the last available value is presented. 
   -
Only visits corresponding to Induction/Consolidation phase are displayed. 
   - Perc.: Percentage.
   * For Arm 2 only.
Programming note:  
Repeat for ARM 1, ARM 2, Randomized Not Randomized
For: HDL (mmol/L), LDL (mmol/L), Glucose (mmol/L), Microalbumin (mg/L), HbA1c (%)


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Table 14.3-9.2.1 Total cholesterol shift table based on specific levels during Induction Consolidation – Full 
Analysis Set
                       ____ Baseline ___                          Worst post-baseline value _____________________
                                                             Normal                
                                                        cholesterolemia       Hypercholesterolemia      Missing
   Treatment                                      n          n   (%)              n   (%)                n 
________________________________________________________________________________________________________________
          
Arm 1               Normal cholesterolemia       xx         xx (xx.x)             xx (xx.x)               xx 
     (N=xxx)        Hypercholesterolemia         xx         xx (xx.x)             xx (xx.x)               xx 
                    Missing                      xx         xx (xx.x)             xx (xx.x)               xx 
                    Total                        xx         xx (xx.x)             xx (xx.x)               xx 
Arm 2               Normal cholesterolemia       xx         xx (xx.x)             xx (xx.x)               xx 
     (N=xxx)        Hypercholesterolemia         xx         xx (xx.x)             xx (xx.x)               xx 
                    Missing                      xx         xx (xx.x)             xx (xx.x)               xx 
                    Total                        xx         xx (xx.x)             xx (xx.x)               xx 
Randomized          Normal cholesterolemia       xx         xx (xx.x)             xx (xx.x)               xx 
     (N=xxx)        Hypercholesterolemia         xx         xx (xx.x)             xx (xx.x)               xx 
                    Missing                      xx         xx (xx.x)             xx (xx.x)               xx 
                    Total                        xx         xx (xx.x)             xx (xx.x)               xx 
Not Randomized      Normal cholesterolemia       xx         xx (xx.x)             xx (xx.x)               xx 
     (N=xxx)        Hypercholesterolemia         xx         xx (xx.x)             xx (xx.x)               xx 
                    Missing                      xx         xx (xx.x)             xx (xx.x)               xx 
                    Total                        xx         xx (xx.x)             xx (xx.x)               xx 
Total               Normal cholesterolemia       xx         xx (xx.x)             xx (xx.x)               xx 
     (N=xxx)        Hypercholesterolemia         xx         xx (xx.x)             xx (xx.x)               xx 
                    Missing                      xx         xx (xx.x)             xx (xx.x)               xx 
                    Total                        xx         xx (xx.x)             xx (xx.x)               xx 
                                                                                                                            
- Baseline is defined as the last available assessment before or at date of start of study treatment.
- Normal cholesterolemia defined as total cholesterol <=5.2 mmol/L; Hypercholesterolemia defined as total cholesterol >5.2        
mmol/L.
- Percentage calculated by row, based on number of available patients at baseline and at least one non-missing post baseline 
value, (1-24 months for Arm 1, Not Randomized and Total, 1-36 months for Randomized and Arm 2).
<<Programming note: use NTCHOBAS, NTCHOPSTin A_LRS>>


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Table 14.3-9.2.2 Total cholesterol shift table based on specific levels during TFR phase  – Subset of Full 
Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.3-9.2.1, for Arm 1, Arm 2 and Total, using NTCHOBAS2, NTCHOPST2 in A_LRS and 
footnotes:
- Baseline is defined as the last available assessment before or at date of start of study treatment.
- Normal cholesterolemia defined as total cholesterol <=5.2 mmol/L; Hypercholesterolemia defined as total cholesterol >5.2        
mmol/L.
- Percentage calculated by row, based on number of available patients at baseline and at least one non-missing post baseline 
value, (1-36 months for Arm 1, 1-24 months for Total and Arm 2).>>
Table 14.3-9.2.3 Total cholesterol shift table based on specific levels during Re-treatment phase  – Subset of 
Full Analysis Set entering the Re-treatment phase
<< Programming note: Same shell as table 14.3-9.2.1, for Arm 1, Arm 2 and Total, using NTCHOBAS3, NTCHOPST3 in A_LRS and 
footnotes:
- Baseline is defined as the last available assessment before or at date of start of study re-treatment.
- Normal cholesterolemia defined as total cholesterol <=5.2 mmol/L; Hypercholesterolemia defined as total cholesterol >5.2        
mmol/L.
- Percentage calculated by row, based on number of available patients at baseline and at least one non-missing post baseline 
value, (1-36 months for Arm 1, 1-24 months for Total and Arm 2).>>
Table 14.3-9.2.4 Total cholesterol shift table based on specific levels during TFR phase, SDV sensitivity  –
Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as Table 14.3-9.2.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-9.2.5 Total cholesterol shift table based on specific levels during Re-treatment phase, SDV 
sensitivity  – Subset of Full Analysis Set entering the Re-treatment phase
<< Programming note: Same shell as Table 14.3-9.2.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-10.1.1 Fasting glucose shift table based on specific levels during Induction Consolidation – Full 
Analysis Set 
                          ____ Baseline ___    ___            Worst post-baseline value ______________________
                                                                        
                                             Normal glycemia   Hyperglycemia      Diabetes       Missing
   Treatment                             n     n   (%)          n   (%)            n  (%)          n 
Arm 1               Normal glycemia     xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
      (N=xxx)       Hyperglycemia       xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx
                    Diabetes            xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx
                    Missing             xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
                    Total               xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
Arm 2               Normal glycemia     xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
      (N=xxx)       Hyperglycemia       xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx
                    Diabetes            xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx
                    Missing             xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
                    Total               xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
Randomized          Normal glycemia     xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
      (N=xxx)       Hyperglycemia       xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx
                    Diabetes            xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx
                    Missing             xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
                    Total               xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
Not Randomized     Normal glycemia     xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
      (N=xxx)       Hyperglycemia       xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx
                    Diabetes            xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx
                    Missing             xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
                    Total               xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
Total               Normal glycemia     xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
      (N=xxx)       Hyperglycemia       xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx
                    Diabetes            xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx
                    Missing             xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
                    Total               xx     xx (xx.x)       xx (xx.x)          xx (xx.x)       xx 
- Baseline is defined as the last available assessment before or at date of start of study treatment.
- Normal glycemia defined as fasting glucose <5.6 mmol/L; Hyperglycemia defined as fasting glucose >=5.6-6.9 mmol/L; Diabetes 
defined as fasting glucose >6.9 mmol/L.
- Percentage calculated by row, based on number of available patients at baseline and at least one
  non-missing post baseline value, (1-24 months for Arm 1, Not Randomized and Total, 1-36 months for Arm 2).


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<<Programming note: use NGLUBAS and  NGLUPST in A_LRS >>
Table 14.3-10.1.2 Fasting glucose shift table based on specific levels during TFR phase  – Subset of Full 
Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.3-10.1.1, for Arm 1, Arm 2 and Total, using NGLUBAS2 and  NGLUPST2 in A_LRS and 
footnotes:
- Baseline is defined as the last assessment in Ind/Cons phase
- Normal glycemia defined as fasting glucose <5.6 mmol/L; Hyperglycemia defined as fasting glucose >=5.6-6.9 mmol/L; Diabetes 
defined as fasting glucose >6.9 mmol/L.
- Percentage calculated by row, based on number of available patients at baseline and at least one.
  non-missing post baseline value, (1-24 months for Arm 1, 1-36 months for Total and Arm 2).>>
Table 14.3-10.1.3 Fasting glucose shift table based on specific levels during Re-treatment phase  – Subset of 
Full Analysis Set entering the Re-treatment phase
<< Programming note: Same shell as table 14.3-10.1.1, for Arm 1, Arm 2 and Total, using NGLUBAS3 and  NGLUPST3 in A_LRS and 
footnotes:
- Baseline is defined as the last available assessment before or at date of start of study re-treatment.- Normal glycemia 
defined as fasting glucose <5.6 mmol/L; Hyperglycemia defined as fasting glucose >=5.6-6.9 mmol/L; Diabetes defined as 
fasting glucose >6.9 mmol/L
- Percentage calculated by row, based on number of available patients at baseline and at least one
  non-missing post baseline value, (1-24 months for Arm 1, 1-36 months for Total and Arm 2).>>
Table 14.3-10.1.4 Fasting glucose shift table based on specific levels during TFR phase, SDV sensitivity   –
Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as Table 14.3-10.1.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-10.1.5 Fasting glucose shift table based on specific levels during Re-treatment phase, SDV 
sensitivity   – Subset of Full Analysis Set entering the Re-treatment phase
<< Programming note: Same shell as Table 14.3-10.1.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-11.1 Vital Signs during Induction Consolidation – Full Analysis Set
Parameter 
Visit
Arm 1 
N=xxx
Arm 2 
N=xxx
Randomized
N=xxx
Not Randomized
N=xxx
Total
N=xxx
Body temperature (C)
Baseline
n              
xx
xx
xx
xx
xx
Missing
xx
xx
xx
xx
xx
Mean           
xx.x
xx.x
xx.x
xx.x
xx.x
SD             
x.xx
x.xx
x.xx
x.xx
x.xx
25th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Median         
xx.x
xx.x
xx.x
xx.x
xx.x
75th Percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Min, Max
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
Month 3
n              
xx
xx
xx
xx
xx
...
...
...
...
...
...
...
Month 24 
n              
xx
xx
xx
xx
xx
...
...
...
...
...
...
Month 27 
n              
Not applicable
xx
xx
Not applicable
xx
...
...
...
...
...
Month 30 
n              
Not applicable
xx
xx
Not applicable
xx
...
...
...
...
...
Month 33 
n              
Not applicable
xx
xx
Not applicable
xx
...
...
...
...
Month 36 
n              
Not applicable
xx
xx
Not applicable
xx
...
...
...
...


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Change from 
Baseline to 
Month 3
n              
xx
xx
xx
xx
xx
...
...
...
...
...
...
...
Change from 
Baseline to 
Month 36 
n              
Not applicable
xx
xx
Not applicable
xx
...
...
...
...
Sitting pulse (bpm)
Baseline
n              
xx
xx
xx
xx
xx
...
...
...
...
...
...
...
Sitting blood 
pressure Systolic 
(mmHg)
Baseline
n              
xx
xx
xx
xx
xx
...
...
...
...
...
...
...
Sitting blood 
pressure Diastolic 
(mmHg)
Baseline
n              
xx
xx
xx
xx
xx
...
...
...
...
...
...
...
-
Baseline is defined as the last available assessment before or at date of start of study treatment
-
Change from baseline: post baseline – baseline.


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<<Programming note: use 
Body Temperature:    BTP1N (for PHASE=1), BASETP1N, CHGTP1N,               
Sitting pulse:              SPUNT1C (for PHASE=1), BASEPS1N, CHGPS1N 
Sitting Diast BP:       STNDBP1N (for PHASE=1), BASEDB1N, CHGDB1N  
Sitting Syst BP:        STNSBP1N (for PHASE=1) , BASESB1N, CHGSB1N 
   from A_VSN
For Missing use only records done( MRKEVL1C = 1 = Crossed) >>


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Table 14.3-11.2 Vital Signs during TFR phase – Subset of Full Analysis Set entering the TFR phase
<< Same shell as table 14.3-11.1, for Arm 1, Arm 2 and Total, using 
Body Temperature:    BTP1N (for PHASE=2), BASETP2N, CHGTP2N, 
Sitting pulse:  
      SPUNT1C (for PHASE=2), BASEPS2N, CHGPS2N
Sitting Syst BP:         STNSBP1N (for PHASE=2), BASESB2N, CHGSB2N   
Sitting Diast BP:       STNDBP1N (for PHASE=2), BASEDB2N, CHGDB2N  
   from A_VSN 
Change footnote to "Baseline is defined as the last treatment record in Ind/Cons phase”>>
Table 14.3-11.3 Vital Signs during Re-treatment phase  – Subset of Full Analysis Set entering the Re-
treatment phase
<< Same shell as table 14.3-11.1, for Arm 1, Arm 2 and Total, using:
Body Temperature:    BTP1N (for PHASE=3), BASETP3N, CHGTP3N, 
Sitting pulse:  
       SPUNT1C (for PHASE=3),  BASEPS3N, CHGPS3N
Sitting Syst BP:       STNSBP1N (for PHASE=3), BASESB3N, CHGSB3N   
Sitting Diast BP:      STNDBP1N (for PHASE=3), BASEDB3N, CHGDB3N  
  from A_VSN 
Change footnote to "Baseline is defined as the first treatment record during Re-treatment”>>


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Table 14.3-11.4 Vital Signs during TFR phase, SDV sensitivity – Subset of Full Analysis Set entering the TFR 
phase
<< Programming note: Same shell as Table 14.3-11.2, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.
Table 14.3-11.5 Vital Signs during Re-treatment phase, SDV sensitivity – Subset of Full Analysis Set entering 
the Re-treatment phase
<< Programming note: Same shell as Table 14.3-11.3, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-12.1 Survival follow-up – Full Analysis Set
Visit
Arm 1 
N=xxx
n (%)
Arm 2 
N=xxx
n (%)
Randomized
N=xxx
n (%)
Not 
Randomized
N=xxx
n (%)
Total
N=xxx
n (%)
FU-Month 3
N=xx
N=xx
N=xx
N=xx
N=xx
Alive
Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
No
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Lost to follow-up
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Did patient undergo stem cell transplant?
Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
No
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Is the disease progressing to AP/BP ?
   Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   No
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Is the patient receiving any TKI treatment ?
   Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   No
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
     If Yes
         Nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
         Imatinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
         Other
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
FU-Month 6
N=xx
N=xx
N=xx
N=xx
N=xx
Patient alive


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Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
...
...
...
...
...
...
FU-Month 36
Alive
N=xx
N=xx
N=xx
N=xx
N=xx
Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
...
...
...
...
...
...
- Percentages calculated over available records for each FU visit.
Table 14.3-12.2 Survival follow-up, SDV sensitivity  – Full Analysis Set
<< Programming note: Same shell as Table 14.3-12.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Table 14.3-13.1 Safety follow-up – Full analysis Set
Safety follow up perfomred? 
Arm 1 
N=xxx
n (%)
Arm 2 
N=xxx
n (%)
Randomized
N=xxx
n (%)
Not Randomized
N=xxx
n (%)
Total
N=xxx
n (%)
Yes, During Clinical visit
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Yes, During Telephone call
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
No
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
   In case of Telephone call, 
    Medical intervention necessary
         Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
         No
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Table 14.3-13.2 Safety follow-up, SDV sensitivity  – Full analysis Set
<< Programming note: Same shell as Table 14.3-13.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19.


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Section 14.3.1 – Displays of adverse events
Figures (Section 14.3.1)
Figure 14.3.1-1.1 Kaplan-Meier analysis of time-to-first CVEs during the pre-randomization
Induction/Consolidation phase – Full Analysis Set
<< Programming note: x-axis in Months, from 0 to 24 months >>
<< Programming note: 3 curves on the same plot: one for arm 1 patient and one for arm 2 patients, one for Not Randomized 
patients>>
Add footnote:” - Presenting CVEs occurred within Pre-Randomization Ind/Cons phase only, excluding additional +30 days period 
used in TEAE outputs.”


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Figure 14.3.1-1.2 Kaplan-Meier analysis of time-to-first CVEs during the post-randomization consolidation 
phase (ARM 2) – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: x-axis in Months, from 24 to 36 
months >>
Add footnote: “- Presenting CVEs occurred within Post-Randomization consolidation phase only, excluding additional +30 days 
period used in TEAE outputs.”


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Figure 14.3.1-1.3 Kaplan-Meier analysis of time-to-first CVEs during the the TFR phase – Subset of Full Analysis 
Set entering the TFR phase
<< Programming note: 
The axis label should “Time since start of TFR phase (months)” 
Months 0-36 for Arm 1, Months 0-24 for Arm 2
Split the curve into two: one for arm 1 patient and one for arm 2 patients >> Months 0-36 for Arm 1, Months 0-24 for Arm 2>>
Figure 14.3.1-1.4 Kaplan-Meier analysis of time-to-first CVEs during the re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase
<< Programming note: The axis label should “Time since start of Re-treatment phase (months)” 
Months 0-36 for Arm 1, Months 0-24 for Arm 2
Split the curve into two: one for arm 1 patient and one for arm 2 patients >> Months 0-36 for Arm 1, Months 0-24 for Arm 2>>
Add footnote: “- Presenting CVEs occurred within Re-treatment phase only, excluding additional +30 days period used in TEAE 
outputs.“


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Figure 14.3.1-2.1 Number of sorted events by HIS CD34+/CD38+ cells 


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Figure 14.3.1-2.2 Number of sorted events by PCR CD34+/CD38+ cells
<< Programming note: Same shell as Figure 14.3.1-2.1 replacing “HIS” by “PCR” >>
Figure 14.3.1-3.1 Number of sorted events by HIS CD34+/CD38- cells
<< Programming note: Same shell as Figure 14.3.1-2.1 replacing “CD34+/CD38+” by “CD34+/CD38-” >>
Figure 14.3.1-3.2 Number of sorted events by PCR CD34+/CD38- cells
<< Programming note: Same shell as Figure 14.3.1-2.2 replacing “CD34+/CD38+” by “CD34+/CD38-” >>
Figure 14.3.1-4.1 Number of sorted events by HIS Immunophenotypically aberrant CD34+ cells 
<< Programming note: Same shell as Figure 14.3.1-2.1 replacing “CD34+/CD38+” by “Immunophenotypically aberrant CD34+” >>
Figure 14.3.1-4.2 Number of sorted events by PCR Immunophenotypically aberrant CD34+ cells 
<< Programming note: Same shell as Figure 14.3.1-2.2 replacing “CD34+/CD38+” by “Immunophenotypically aberrant CD34+>>
Figure 14.3.1-5.1 Number of sorted events by HIS Immunophenotypically aberrant CD34- cells 
<< Programming note: Same shell as Figure 14.3.1-2.1 replacing “CD34+/CD38+” by “Immunophenotypically aberrant CD34-” >>
Figure 14.3.1-5.2 Number of sorted events by PCR Immunophenotypically aberrant CD34- cells
<< Programming note: Same shell as Figure 14.3.1-2.2 replacing “CD34+/CD38+” by “Immunophenotypically aberrant CD34->>


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Figure 14.3.1-6.1 Number of HIS+ subjects CD34+/CD38+ cells – LSC substudy Full Analysis Set


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Figure 14.3.1-6.2 Number of PCR subjects CD34+/CD38+ cells – LSC substudy Full Analysis Set
<< Programming note: Same shell as Figure 14.3.1-6.1 replacing “HIS+” by “PCR” >>
Figure 14.3.1-7.1 Number of HIS+ subjects CD34+/CD38- cells – LSC substudy Full Analysis Set
<< Programming note: Same shell as Figure 14.3.1-6.1 replacing “CD34+/CD38+” by “CD34+/CD38-” >>
Figure 14.3.1-7.2 Number of PCR subjects CD34+/CD38- cells – LSC substudy Full Analysis Set
<< Programming note: Same shell as Figure 14.3.1-6.2 replacing “CD34+/CD38+” by “CD34+/CD38-” >>
Figure 14.3.1-8.1 Number of HIS+ subjects Immunophenotypically aberrant CD34+ cells – LSC substudy Full 
Analysis Set
<< Programming note: Same shell as Figure 14.3.1-6.1 replacing “CD34+/CD38+” by “Immunophenotypically aberrant CD34+” >>
Figure 14.3.1-8.2 Number of PCR subjects Immunophenotypically aberrant CD34+ cells – LSC substudy Full 
Analysis Set
<< Programming note: Same shell as Figure 14.3.1-6.2 replacing “CD34+/CD38+” by “Immunophenotypically aberrant CD34+” >>
Figure 14.3.1-9.1 Number of HIS+ subjects Immunophenotypically aberrant CD34- cells – LSC substudy Full 
Analysis Set
<< Programming note: Same shell as Figure 14.3.1-6.1 replacing “CD34+/CD38+” by “Immunophenotypically aberrant CD34-” >>
Figure 14.3.1-9.2 Number of PCR subjects Immunophenotypically aberrant CD34- cells – LSC substudy FAS
<< Programming note: Same shell as Figure 14.3.1-6.2 replacing “CD34+/CD38+” by “Immunophenotypically aberrant CD34-” >>


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Figure 14.3.1-10 Number of patients with detectable LSC – LSC substudy Full Analysis Set


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Tables (Section 14.3.1)
Table 14.3.1-1.1 Overall summary of treatment-emergent adverse events occurring during pre-randomization 
Induction/consolidation phase – Full Analysis Set 
Adverse event category
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
Not Randomized
N=xx
Total
N=xx
Any adverse events
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any AE of special interest
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Grading of AEs
NCI-CTCAE Grade 4
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 3
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs suspected to be related to nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs leading to study drug discontinuation
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs requiring dosage adjustment or temporarily 
interruption
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs suspected to be related to nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs leading to study drug discontinuation
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
- For patient #
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.


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Only TEAEs from pre-rand Ind./Cons. phase have been included in this table. A pat. with mult. occur. of an AE
is counted only once in the AE category. Percentage based on the number of patients included in the analysis population (N). 
AESI CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as 
described in the Case Retrieval Sheet. Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 
36/24 months. Patient #
reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been 
reported as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
For patient #
 AE “PHLEGMON FOOT - BIG TOE RIGHT” is reported as PT “Cellulitis” in the AE listing while 
it is reported as PT “Osteoarthritis” in the SAE listing. PT for the same AE has been wrongly decoded and
reconciliation was not requiring a perfect match of the PT. 


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Table 14.3.1-1.2 Overall summary of treatment-emergent adverse events occurring during post-randomization
consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to Arm 2
Adverse event category
N=xx
Any adverse events
xx (xx.x)
Any AE of special interest
xx (xx.x)
Grading of AEs
NCI-CTCAE Grade 4
xx (xx.x)
NCI-CTCAE Grade 3
xx (xx.x)
NCI-CTCAE Grade 2
xx (xx.x)
NCI-CTCAE Grade 1
xx (xx.x)
NCI-CTCAE Missing
xx (xx.x)
Death
xx (xx.x)
AEs suspected to be related to nilotinib
xx (xx.x)
AEs leading to study drug discontinuation
xx (xx.x)
AEs requiring dosage adjustment or temporarily interruption
xx (xx.x)
Serious AEs
xx (xx.x)
Serious AEs suspected to be related to nilotinib
xx (xx.x)
Serious AEs leading to study drug discontinuation
xx (xx.x)
- For patient #
, due to reconciliation discrepancies, safety database 
reported AE term “Endometriosis” as a SAE, while in clinical database this AE was not 
recorded as an SAE.
- Only treatment emergent adverse events from post-randomization consolidation phase are included in this table.
- A patient with multiple occurrences of an AE is counted only once in the AE category.              
- Percentage based on the number of patients included in the analysis population (N).


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- AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described 
in the Case Retrieval Sheet. Patients randomized to Arm 2 have 12 months of treatment post-randomization and a maximum of 24 
months of re-treatment. For patient
 AE “PHLEGMON FOOT - BIG TOE RIGHT” is reported as PT “Cellulitis” in the AE 
listing while it is reported as PT “Osteoarthritis” in the SAE listing. PT for the same AE has been wrongly decoded and 
reconciliation was not requiring a perfect match of the PT.


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Table 14.3.1-1.3 Overall summary of treatment-emergent adverse events occurring during re-treatment phase 
– Subset of Full Analysis Set entering the re-treatment phase
Adverse event category
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Any adverse events
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any AE of special interest
xx (xx.x)
xx (xx.x)
xx (xx.x)
Grading of AEs
NCI-CTCAE Grade 4
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 3
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs suspected to be related to nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs leading to study drug discontinuation
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs requiring dosage adjustment or temporarily interruption
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs suspected to be related to nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs leading to study drug discontinuation
xx (xx.x)
xx (xx.x)
xx (xx.x)
- Only treatment emergent adverse events from re-treatment phase are included in this table.
- A patient with multiple occurrences of an AE is counted only once in the AE category.
- Percentage based on the number of patients included in the analysis population (N).
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
- Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
- AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described 
in the Case Retrieval Sheet.


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Table 14.3.1-1.4 Overall summary of adverse events occurring during TFR phase – Subset of Full Analysis Set 
entering the TFR phase
Adverse event category
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Any adverse events
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any AE of special interest
xx (xx.x)
xx (xx.x)
xx (xx.x)
Grading of AEs
NCI-CTCAE Grade 4
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 3
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Grade 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
NCI-CTCAE Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
Death
xx (xx.x)
xx (xx.x)
xx (xx.x)
AEs suspected to be related to nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
  AE occurring within 30 days after TFR start end
xx (xx.x)
xx (xx.x)
xx (xx.x)
  AE occurring after 30 days after TFR start end
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs
xx (xx.x)
xx (xx.x)
xx (xx.x)
Serious AEs suspected to be related to nilotinib
xx (xx.x)
xx (xx.x)
xx (xx.x)
  AE occurring within 30 days after TFR start 
xx (xx.x)
xx (xx.x)
xx (xx.x)
  AE occurring after 30 days after TFR start 
xx (xx.x)
xx (xx.x)
xx (xx.x)
- Only adverse events from TFR phase are included in this table. 
- A patient with multiple occurrences of an AE is counted only once in the AE category.
- Percentage based on the number of patients included in the analysis population (N).
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
- Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
- AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described 
in the Case Retrieval Sheet.


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Table 14.3.1-2.1 Overall summary of frequent [1] treatment-emergent adverse events occurring during pre-
randomization Induction/consolidation phase – Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-1.1   adding the following footnote:
Only TEAEs from pre-rand Ind./Cons. phase have been included in this table. A pat. with mult. occur. of an AE
is counted only once in the AE category. Perc. based on the number of pat. included in the analysis pop. (N). 
AESI CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described in the 
CRS. Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. Patient #
 reported as disc. 
Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported as disc. Ind/Cons phase due to Disease Progression, 
progression to Blast Crisis, as per Prot. For patient #
 AE “PHLEGMON FOOT - BIG TOE RIGHT” is reported as PT 
“Cellulitis” in the AE listing while it is reported as PT “Osteoarthritis” in the SAE listing. PT for the same AE has been 
wrongly decoded and reconciliation was not requiring a perfect match of the PT.
[1] Frequent AE defined as an AE present at 5% or more for at least one treatment Arm.
Add following footnote at the end of last page: 
- For patient #
 due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.
Table 14.3.1-2.2 Overall summary of frequent [1] treatment-emergent adverse events occurring during post-
randomization consolidation phase (ARM 2) – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-1.2   adding the following footnote:
[1] Frequent AE defined as an AE present at 5% or more of the Arm2 patients.
Table 14.3.1-2.3 Overall summary of frequent [1] treatment-emergent adverse events occurring during re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-1.3   adding the following footnote:
[1] Frequent AE defined as an AE present at 5% or more for at least one treatment Arm.


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Table 14.3.1-2.4 Overall summary of frequent [1] adverse events occurring during TFR phase – Subset of Full 
Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-1.4   adding the following footnote:
[1] Frequent AE defined as an AE present at 5% or more for at least one treatment Arm.


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Table 14.3.1-3.1.1 Treatment Emergent adverse events incidence, regardless of study drug relationship, 
occurring during pre-randomization Induction/consolidation phase by system organ class and 
preferred term - overall and maximum grade 3/4 – Full Analysis Set
Arm 1
N=xxx
Arm 2 
N=xxx
Randomized
N=xxx
Not Randomized
N=xxx
Total
N=xxx
Primary system 
organ class
Preferred term
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
Any Primary 
system organ 
class
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Cardiac 
disorders
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Angina pectoris
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Bradycardia NOS
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Oedema NOS
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Tachycardia NOS
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
- For patient #
due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.
- Only TEAEs from pre-rand. Ind./Cons. phase have been included. Primary SOC are pres. alphab.; PTs are sorted
within primary SOC in desc. freq. of ‘All grades’ column. Percentage based on the pop. number (N). Treatment 
Arm 1/Arm 2: 24/36 months, Re-trt max Arm 1/Arm 2: 36/24 months. A patient with mult. occur. of an AE is counted 
Only once in the AE cat.; A patient with mult. AEs within a primary SOC is counted only once in the total row. AEs 
occurring more than 30 days after last study trt exposure date are not summarized. Patient #
 reported as
disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported as disc. Ind/Cons phase due to Disease 
Progression, progression to Blast Crisis, as per Prot. For patient #
AE “PHLEGMON FOOT - BIG TOE RIGHT”
is reported as PT “Cellulitis” in the AE listing while it is reported as PT “Osteoarthritis” in the SAE listing. 
PT for the same AE has been wrongly decoded and reconciliation was not requiring a perfect match of the PT.


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Protocol No CAMN107AIC0
Table 14.3.1-3.1.2 Treatment Emergent adverse events occurence, regardless of study drug relationship, 
occurring during pre-randomization Induction/consolidation phase by system organ class and 
preferred term - overall and maximum grade 3/4 – Full Analysis Set
<< Programming note: Same shell as table 14.3.1-3.1.1   but without percentages and use footnotes:
- Only treatment emergent adverse events from pre-rand. ind./cons. phase have been included in this table.
- Primary SOC are presented alphabetically; preferred terms are sorted within primary SOC in desc. frequency
of ‘All grades’ column. Treatment Arm 1/Arm 2: 24/36 months, Re-trt max Arm 1/Arm 2: 36/24 months. AEs 
occurring more than 30 days after last study trt exposure date are not summarized.
- Patient #
reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported
as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
- For patient #
AE “PHLEGMON FOOT - BIG TOE RIGHT” is reported as PT “Cellulitis” in the AE listing 
while it is reported as PT “Osteoarthritis” in the SAE listing. PT for the same AE has been wrongly 
decoded and reconciliation was not requiring a perfect match of the PT. 
Add following footnote at the end of last page: 
- For patient #
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.


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Protocol No CAMN107AIC0
Table 14.3.1-3.2.1 Treatment Emergent adverse events incidence, regardless of study drug relationship, 
occurring during post-randomization consolidation phase (ARM 2) by system organ class and 
preferred term - overall and maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
Arm 2
N=xxx
Primary system organ class
Preferred term
All 
grades 
n (%)
Grade
3/4  
n (%)
Any Primary system organ class
xx (xx.x)
xx (xx.x)
Cardiac disorders
xx (xx.x)
xx (xx.x)
Angina pectoris
xx (xx.x)
xx (xx.x)
Bradycardia NOS
xx (xx.x)
xx (xx.x)
Oedema NOS
xx (xx.x)
xx (xx.x)
Tachycardia NOS
xx (xx.x)
xx (xx.x)
...
- Only treatment emergent adverse events from post-rand. cons. phase (ARM 2) are included in this table.
- Primary system organ classes are presented alphabetically; preferred terms are sorted within primary 
system organ class in descending frequency of ‘All grades’ column.
- Percentage based on the number of patients included in the analysis population (N).
- Treatment post-randomization Arm 2: 12 months, Re-treatment max Arm 2: 24 months. 
- A patient with multiple occurrences of an AE is counted only once in the AE category.       
- A patient with multiple adverse events within a primary system organ class is counted only once in the total row.
- Adverse events occurring more than 30 days after last study treatment exposure date are not summarized.


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Table 14.3.1-3.2.2 Treatment Emergent adverse events occurence, regardless of study drug relationship, 
occurring during post-randomization consolidation phase (ARM 2) by system organ class and 
preferred term - overall and maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-3.2.1    but without percentages and use footnotes:
- Only treatment emergent adverse events from post-rand. cons. phase (ARM 2) are included in this table.
- Primary system organ classes are presented alphabetically; preferred terms are sorted within primary system organ class in 
  descending frequency of ‘All grades’ column.
- Treatment post-randomization Arm 2: 12 months, Re-treatment max Arm 2: 24 months. 
- Adverse events occurring more than 30 days after last study treatment exposure date are not summarized.


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Protocol No CAMN107AIC0
Table 14.3.1-3.3.1 Treatment-emergent adverse events incidence, regardless of study drug relationship, by 
system organ class and preferred term during re-treatment phase – overall and maximum grade 3/4 –
Subset of Full Analysis Set entering the re-treatment phase
Primary system organ class
Preferred term
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
All grades
n (%)
Grade 3/4
n (%)
All grades
n (%)
Grade 3/4
n (%)
All grades
n (%)
Grade 3/4
n (%)
Any primary system organ class
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Cardiac disorders
Angina pectoris
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Bradycardia NOS
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Oedema NOS
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Tachycardia NOS
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
etc.
- Only treatment emergent adverse events from re-treatment phase are included in this table.
- Primary system organ classes are alphabetically presented; preferred terms are sorted within primary system organ class in 
  descending frequency of ‘All grades’ column.
- Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- A patient with multiple occurrences of an AE is counted only once in the AE category.       
- A patient with multiple AE within a primary system organ class is counted only once in the total row.
- Adverse events occurring more than 30 days after last study treatment exposure date are not summarized.


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Protocol No CAMN107AIC0
Table 14.3.1-3.3.2 Treatment-emergent adverse events occurrence, regardless of study drug relationship, by 
system organ class and preferred term during re-treatment phase – overall and maximum grade 3/4 –
Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.3.1 but without percentages and use footnotes:
- Only treatment emergent adverse events from re-treatment phase are included in this table.
- Primary system organ classes are alphabetically presented; preferred terms are sorted within primary system organ class in 
  descending frequency of ‘All grades’ column.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- Adverse events occurring more than 30 days after last study treatment exposure date are not summarized.
Table 14.3.1-3.4.1 Adverse events incidence, regardless of study drug relationship, by system organ class and 
preferred term during TFR phase – overall and maximum grade 3/4 – Subset of Full Analysis Set 
entering the TFR phase
<< Programming note: Same shell as table 14.3.1-3.3.1   and use footnote:
- Only adverse events from TFR phase are included in this table.
- Primary system organ classes are alphabetically presented; preferred terms are sorted within primary system organ class in 
  descending frequency of ‘All grades’ column.
- Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- A patient with multiple occurrences of an AE is counted only once in the AE category.       
- A patient with multiple AE within a primary system organ class is counted only once in the total row.
Table 14.3.1-3.4.2 Adverse events occurrence, regardless of study drug relationship, by system organ class 
and preferred term during TFR phase – overall and maximum grade 3/4 – Subset of Full Analysis Set 
entering the TFR phase
<< Programming note: Same shell as table 14.3.1-3.4.3 but without percentages and use footnotes:
- Only adverse events from TFR phase are included in this table.
- Primary system organ classes are presented alphabetically; preferred terms are sorted within primary system organ class in 
  descending frequency of ‘All grades’ column.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 


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Protocol No CAMN107AIC0
Table 14.3.1-3.5.1 Frequent [1] Treatment Emergent adverse events incidence, regardless of study drug 
relationship occurring during pre-randomization Induction/consolidation phase by system organ class 
and preferred term - overall and maximum grade 3/4 – Full Analysis Set
<< Programming note: Same shell as table 14.3.1-3.1.1 >>  
Only TEAEs from pre-rand Ind./Cons. phase have been included in this table. A pat. with mult. occur. of an AE
is counted only once in the AE category. Perc. based on the number of pat. included in the analysis pop. (N). 
AESI CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described in the 
CRS. Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months.
Patient #
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported as disc. 
Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot. For patient 
 AE “PHLEGMON 
FOOT - BIG TOE RIGHT” is reported as PT “Cellulitis” in the AE listing while it is reported as PT “Osteoarthritis” in the SAE 
listing. PT for the same AE has been wrongly decoded and reconciliation was not requiring a perfect match of the PT.
[1] Frequent AE defined as an AE present at 5% or more for at least one treatment Arm.
Programming Note: Consider only AEs with >5% for Total group at the level of Preferred Term.
Re-calculate Primay SOC and Any Primary SOC frequencies accordingly, based on the selected AEs only.
Table 14.3.1-3.5.2 Frequent [1] Treatment Emergent adverse events incidence, regardless of study drug 
relationship occurring during post-randomization consolidation phase (ARM 2) by system organ class 
and preferred term- overall and maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 
2
<< Programming note: Same shell as table 14.3.1-3.2.1   adding the following footnote:
[1] Frequent AE defined as an AE present at 5% or more of the Arm2 patients.
Programming Note: Consider only AEs with >5% for Total group at the level of Preferred Term.
Re-calculate Primay SOC and Any Primary SOC frequencies accordingly, based on the selected AEs only.


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Table 14.3.1-3.5.3 Frequent [1] Treatment Emergent adverse events incidence, regardless of study drug 
relationship occurring during re-treatment phase by system organ class and preferred term- overall 
and maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.3.1   adding the following footnote:
[1] Frequent AE defined as an AE present at 5% or more for at least one treatment Arm.
Programming Note: Consider only AEs with >5% for Total group at the level of Preferred Term.
Re-calculate Primay SOC and Any Primary SOC frequencies accordingly, based on the selected AEs only.
Table 14.3.1-3.5.4 Frequent [1] adverse events incidence, regardless of study drug relationship occurring 
during TFR phase by system organ class and preferred term - overall and maximum grade 3/4 – Subset 
of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-3.4.1   adding the following footnote:
[1] Frequent AE defined as an AE present at 5% or more for at least one treatment Arm.
Programming Note: Consider only AEs with >5% for Total group at the level of Preferred Term.
Re-calculate Primay SOC and Any Primary SOC frequencies accordingly, based on the selected AEs only.


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Page 348
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Protocol No CAMN107AIC0
Table 14.3.1-4.1.1 Serious treatment-emergent adverse events incidence, regardless of study drug relationship, 
by system organ class and preferred term during pre-randomization Induction/consolidation phase –
overall and maximum grade 3/4 –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-3.1.1>>
- Only TEAEs from pre-rand. Ind./Cons. phase have been included. Prim. SOC are pres. alphab.; PTs are sorted
within prim. SOC in desc. freq. of ‘All grades’ column. Percentage based on pop. number (N). Treatment Arm 1
/Arm 2: 24/36 months, Re-trt max Arm 1/Arm 2: 36/24 months. A patient with mult. occur. of an AE is counted only 
once in the AE cat.; A pat. with mult. AEs within a prim. SOC is counted only once in the total row. AEs occur. 
more than 30 days after last study trt exposure date are not summarized. Patient #
 reported as disc.
Ind/Cons phase due to AE “
”- G2, should have been reported as disc. Ind/Cons phase due to Disease 
Progression, progr. to Blast Crisis, as per Prot. For patient #
 AE “PHLEGMON FOOT - BIG TOE RIGHT” is 
reported as PT “
” in the AE listing while it is reported as PT “Osteoarthritis” in the SAE listing.
PT for the same AE has been wrongly decoded and reconciliation was not requiring a perfect match of the PT.
Add following footnote at the end of last page: 
- For patient #
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.
Table 14.3.1-4.1.2 Serious treatment-emergent adverse events occurence, regardless of study drug 
relationship, 
by 
system 
organ 
class 
and 
preferred 
term 
during 
pre-randomization 
Induction/consolidation phase – overall and maximum grade 3/4 –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-3.1.2 >>
- Only TEAEs from pre-rand. ind./cons. phase have been included in this table. Prim. SOC are pres. alphabetically;   
preferred terms are sorted within primary system organ class in descending frequency of ‘All grades’ column.                            
- Treatment Arm 1/Arm 2: 24/36 months, treatment free remission max Arm 1/Arm 2: 36/24 months.                                
- Adverse events occurring more than 30 days after last study treatment exposure date are not summarized.                     
Patient #
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported as 
disc. Ind/Cons phase due to Disease Progression, progr. to Blast Crisis, as per Prot. For patient #
AE “PHLEGMON FOOT - BIG TOE RIGHT” is reported as PT “Cellulitis” in the AE listing while it is reported 
as PT “Osteoarthritis” in the SAE listing. PT for the same AE has been wrongly decoded and reconciliation 
was not requiring a perfect match of the PT. 
Add following footnote at the end of last page: 
- For patient 
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.


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Protocol No CAMN107AIC0
Table 14.3.1-4.2.1 Serious treatment-emergent adverse events incidence, regardless of study drug relationship, 
by system organ class and preferred term during post-randomization consolidation phase (ARM 2) –
overall and maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
                                                                         
<< Programming note: Same shell as table 14.3.1-3.2.1>>
Table 14.3.1-4.2.2 Serious treatment-emergent adverse events occurrence, regardless of study drug 
relationship, by system organ class and preferred term during post-randomization consolidation 
phase (ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-3.2.2 >>


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Protocol No CAMN107AIC0
Table 14.3.1-4.3.1 Serious treatment-emergent adverse events incidence, regardless of study drug relationship, 
by system organ class and preferred term during re-treatment phase – overall and maximum grade 3/4 
– Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.3.1 >>
Table 14.3.1-4.3.2 Serious treatment-emergent adverse events occurrence, regardless of study drug 
relationship, by system organ class and preferred term during re-treatment phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.3.2 >>
Table 14.3.1-4.4.1 Serious adverse events incidence, regardless of study drug relationship, by system organ 
class and preferred term during TFR phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-3.4.1>>
Table 14.3.1-4.4.2 Serious adverse events occurence, regardless of study drug relationship, by system organ 
class and preferred term during TFR phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-3.4.2>>


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RAP Module 7.1
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Protocol No CAMN107AIC0
Table 14.3.1-4.5.1 Frequent [1] Serious Treatment Emergent adverse events incidence, regardless of study drug 
relationship occurring during pre-randomization Induction/consolidation phase by system organ class 
and preferred term - overall and maximum grade 3/4 – Full Analysis Set
<< Programming note: Same shell as table 14.3.1-3.5.1>>
Programming Note: Consider only AEs with >5% for one or more treatment Arms at the level of Preferred Term.
Re-calculate Primay SOC and Any Primary SOC frequencies accordingly, based on the selected AEs only.
Table 14.3.1-4.5.2 Frequent [1] Serious Treatment Emergent adverse events incidence, regardless of study drug 
relationship occurring during post-randomization consolidation phase (ARM 2) by system organ class 
and preferred term - overall and maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 
2
<< Programming note: Same shell as table 14.3.1-3.5.2>>
Programming Note: Consider only AEs with >5% for or more treatment Arms at the level of Preferred Term.
Re-calculate Primay SOC and Any Primary SOC frequencies accordingly, based on the selected AEs only.
Table 14.3.1-4.5.3 Frequent [1] Serious Treatment Emergent adverse events incidence, regardless of study drug 
relationship occurring during re-treatment phase by system organ class and preferred term - overall 
and maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.5.3 >>
Programming Note: Consider only AEs with >5% for or more treatment Arms at the level of Preferred Term.
Re-calculate Primay SOC and Any Primary SOC frequencies accordingly, based on the selected AEs only.
Table 14.3.1-4.5.4 Frequent [1] Serious adverse events incidence, regardless of study drug relationship  
occurring during TFR phase by system organ class and preferred term - overall and maximum grade 
3/4 – Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-3.5.4 >>  
Programming Note: Consider only AEs with >5% for or more treatment Arms at the level of Preferred Term.
Re-calculate Primay SOC and Any Primary SOC frequencies accordingly, based on the selected AEs only.


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Protocol No CAMN107AIC0
Table 14.3.1-4.6.1 Serious treatment-emergent adverse events incidence, suspected to be study drug related, 
by system organ class and preferred term during pre-randomization Induction/consolidation phase  –
overall and maximum grade 3/4 –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-3.1.1 >>
- Only TEAEs from pre-rand. Ind./Cons. phase have been included. Primary SOC are pres. alphab.; PTs are sorted
within primary SOC in desc. freq. of ‘All grades’ column. Percentage based on the pop. number (N). Treatment 
Arm 1/Arm 2: 24/36 months, Re-trt max Arm 1/Arm 2: 36/24 months. A patient with mult. occur. of an AE is counted 
Only once in the AE cat.; A patient with mult. AEs within a primary SOC is counted only once in the total row. AEs   
occurring more than 30 days after last study trt exposure date are not summarized. Patient #
 reported as
disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported as disc. Ind/Cons phase due to Disease 
Progression, progression to Blast Crisis, as per Prot. For patient #
 AE “PHLEGMON FOOT - BIG TOE RIGHT”
is reported as PT “Cellulitis” in the AE listing while it is reported as PT “Osteoarthritis” in the SAE listing. 
PT for the same AE has been wrongly decoded and reconciliation was not requiring a perfect match of the PT.
Add following footnote at the end of last page: 
- For patient 
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.
Table 14.3.1-4.6.2 Serious treatment-emergent adverse events occurence, suspected to be study drug related, 
by system organ class and preferred term during pre-randomization Induction/consolidation phase –
overall and maximum grade 3/4 –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-3.1.2 >>
- Only TEAEs from post-randomization consolidation phase are included in this table. A patient with multiple 
occurrences of an AE is counted only once in the AE category. Percentage based on the number of patients included 
in the analysis population (N). AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are
based on grouped MedDRA terms as described in the Case Retrieval Sheet. Patients randomized to Arm 2 have 12 months
of treatment post-randomization and a maximum of 24 months of re-treatment. Patient #
 reported as disc. 
Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported as disc. Ind/Cons phase due to Disease Progression, 
progression to Blast Crisis, as per Prot.
For patient #
AE “PHLEGMON FOOT - BIG TOE RIGHT” is reported as PT 
“Cellulitis” in the AE listing while it is reported as PT “Osteoarthritis” in the SAE listing.    
PT for the same AE has been wrongly decoded and reconciliation was not requiring a perfect match of the PT.
Add following footnote at the end of last page: 
- For patient 
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.


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Page 353
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Protocol No CAMN107AIC0
Table 14.3.1-4.7.1 Serious treatment-emergent adverse events incidence, suspected to be study drug related, 
by system organ class and preferred term during post-randomization consolidation phase (ARM 2) –
overall and maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-3.2.1 >>
Table 14.3.1-4.7.2 Serious treatment-emergent adverse events occurrence, suspected to be study drug related, 
by system organ class and preferred term during post-randomization consolidation phase (ARM 2) –
overall and maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-3.2.2    >>
Table 14.3.1-4.8.1 Serious treatment-emergent adverse events incidence, suspected to be study drug related, 
by system organ class and preferred term during re-treatment phase – overall and maximum grade 3/4 
– Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.3.1 >>
Table 14.3.1-4.8.2 Serious treatment-emergent adverse events occurrence, suspected to be study drug related, 
by system organ class and preferred term during re-treatment phase – overall and maximum grade 3/4 
– Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.3.2>>
Table 14.3.1-4.9.1 Serious adverse events incidence, suspected to be study drug related, by system organ class 
and preferred term during TFR phase – overall and maximum grade 3/4 – Subset of Full Analysis Set 
entering the TFR phase
<< Programming note: Same shell as table 14.3.1-3.4.1 >>


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Protocol No CAMN107AIC0
Table 14.3.1-4.9.2 Serious adverse events occurrence, suspected to be study drug related, by system organ 
class and preferred term during TFR phase – overall and maximum grade 3/4 – Subset of Full Analysis 
Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-3.4.2>>
Table 14.3.1-5.1.1 Treatment-emergent adverse events incidence leading to study drug discontinuation by 
system organ class and preferred term during pre-randomization Induction/Consolidation phase –
overall and maximum grade 3/4 –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-3.1.1>>   
- Only TEAEs from pre-rand. ind./cons. phase have been included in this table. Primary SOC are presented 
alphabetically; PTs are sorted within primary SOC in descending frequency of ‘All grades’ column.
- Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- A patient with multiple occurrences of an AE is counted only once in the AE category.       
- A patient with multiple AEs within a primary system organ class is counted only once in the total row
- Adverse events occurring more than 30 days after last study treatment exposure date are not summarized.
- Patient 
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported 
as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
Add following footnote at the end of last page: 
- For patient #
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.


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Page 355
RAP Module 7.1
6-May-2021 (14:35)
Protocol No CAMN107AIC0
Table 14.3.1-5.1.2 Treatment-emergent adverse events occurence leading to study drug discontinuation by 
system organ class and preferred term during pre-randomization Induction/Consolidation phase –
overall and maximum grade 3/4 –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-3.1.2>>
- Only treatment emergent adverse events from pre-rand. ind./cons. phase have been included in this table.
- Primary system organ classes are presented alphabetically; preferred terms are sorted within primary system 
organ class in descending frequency of ‘All grades’ column.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- Adverse events occurring more than 30 days after last study treatment exposure date are not summarized.
- Patient #
reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported 
as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
Add following footnote at the end of last page: 
- For patient #
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.
Table 14.3.1-5.2.1 Treatment-emergent adverse events incidence leading to study drug discontinuation by 
system organ class and preferred term during post-randomization phase (ARM 2) – overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-3.2.1 >>  
Table 14.3.1-5.2.2 Treatment-emergent adverse events occurrence leading to study drug discontinuation by 
system organ class and preferred term during post-randomization phase (ARM 2)– overall and 
maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-3.2.2 >>


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Table 14.3.1-5.3.1 Treatment-emergent adverse events incidence leading to study drug discontinuation by 
system organ class and preferred term during re-treatment phase – overall and maximum grade 3/4 –
Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.3.1 >>
Table 14.3.1-5.3.2 Treatment-emergent adverse events occurrence leading to study drug discontinuation by 
system organ class and preferred term during re-treatment phase – overall and maximum grade 3/4 –
Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.3.2  >>
Table 14.3.1-6.1.1 Treatment-emergent adverse events incidence requiring dosage adjustment or temporarily 
interruption by system organ class and preferred term during pre-randomization Induction/ 
consolidation phase  – overall and maximum grade 3/4 –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-3.1.1 >>
- Only TEAEs from pre-rand. Ind./Cons. phase have been included. Primary SOC are pres. alphab.; PTs are sorted
within primary SOC in desc. freq. of ‘All grades’ column. Percentage based on the pop. number (N). Treatment 
Arm 1/Arm 2: 24/36 months, Re-trt max Arm 1/Arm 2: 36/24 months. A patient with mult. occur. of an AE is counted 
Only once in the AE cat.; A patient with mult. AEs within a primary SOC is counted only once in the total row. AEs 
occurring more than 30 days after last study trt exposure date are not summarized. Patient #
 reported as
disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported as disc. Ind/Cons phase due to Disease 
Progression, progression to Blast Crisis, as per Prot. For patient #
 AE “PHLEGMON FOOT - BIG TOE RIGHT”
is reported as PT “Cellulitis” in the AE listing while it is reported as PT “Osteoarthritis” in the SAE listing. 
PT for the same AE has been wrongly decoded and reconciliation was not requiring a perfect match of the PT.
Add following footnote at the end of last page:
- For patient #
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.


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Table 14.3.1-6.1.2 Treatment-emergent adverse events occurrence requiring dosage adjustment or temporarily 
interruption 
by 
system 
organ 
class 
and 
preferred 
term 
during 
pre-randomization 
Induction/consolidation phase – overall and maximum grade 3/4 –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-3.1.2 >>
- Only treatment emergent adverse events from pre-rand. ind./cons. phase have been included in this table.
- Primary SOC are presented alphabetically; preferred terms are sorted within primary SOC in desc. frequency
of ‘All grades’ column. Treatment Arm 1/Arm 2: 24/36 months, Re-trt max Arm 1/Arm 2: 36/24 months. AEs 
occurring more than 30 days after last study trt exposure date are not summarized.
- Patient #
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported
as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
- For patient #
 AE “PHLEGMON FOOT - BIG TOE RIGHT” is reported as PT “Cellulitis” in the AE listing 
while it is reported as PT “Osteoarthritis” in the SAE listing. PT for the same AE has been wrongly 
decoded and reconciliation was not requiring a perfect match of the PT. 
Add following footnote at the end of last page: 
- For patient #
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.
Table 14.3.1-6.2.1 Treatment-emergent adverse events incidence requiring dosage adjustment or temporarily 
interruption by system organ class and preferred term during post-randomization consolidation phase 
(ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-3.2.1 >>
Table 14.3.1-6.2.2 Treatment-emergent adverse events occurrence requiring dosage adjustment or temporarily 
interruption by system organ class and preferred term during post-randomization consolidation phase 
(ARM 2) – overall and maximum grade 3/4 – Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-3.2.2>>


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Table 14.3.1-6.3.1 Treatment-emergent adverse events incidence requiring dosage adjustment or temporarily 
interruption by system organ class and preferred term during re-treatment phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.3.1 >>
Table 14.3.1-6.3.2 Treatment-emergent adverse events occurrence requiring dosage adjustment or temporarily 
interruption by system organ class and preferred term during re-treatment phase – overall and 
maximum grade 3/4 – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-3.3.2 >>


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Table 14.3.1-6.4.1 Treatment-emergent adverse events of interest incidence, regardless of study drug 
relationship, by specific group and preferred term during Pre-randomization Induction/consolidation 
phase –by treatment arm, overall and maximum grade 3/4 – Full Analysis Set
        
Arm 1 
N=xxx
Arm 2 
N=xxx
Randomized
N=xxx
Not Randomized
N=xxx
Total
N=xxx
Specific group 
Preferred term
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All AESI
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Group 1
PT1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
PT2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
Group 2
PT1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
PT2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
- Only treatment emergent adverse events from pre-rand. ind./cons. phase have been included in this table.
- Specific groupings are presented alphabetically; preferred terms are sorted within each group in descending 
frequency of ‘All grades’ column. Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- A patient with multiple occurrences of an AE is counted only once in the AE category. A patient with multiple adverse 
events within a group is counted only once in the total row. AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and 
CVEs (others) are based on grouped MedDRA terms as described in the Case Retrieval Sheet. AEs occurring more than 30 days 
after last study treatment exposure date are not summarized.
<<Programming note: The below groups of AEs of special interest will be displayed:
-CVEs (IHD: Ischemic heart disease)
-CVEs (PAOD: Peripheral arterial occlusive disease)
-CVEs (ICE: Ischemic cerebrovascular events)
-CVEs (Others) 


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Table 14.3.1-6.4.2 Treatment-emergent adverse events of interest occurrence, regardless of study drug 
relationship, by specific group and preferred term during Pre-randomization Induction/consolidation 
phase – by treatment arm, overall and maximum grade 3/4 –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-6.4.1   but without percentages, use footnotes:
- Only treatment emergent adverse events from pre-rand. ind./cons. phase have been included in this table.
- Specific groupings are presented alphabetically; preferred terms are sorted within each group in descending frequency of 
‘All grades’ column.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described 
in the Case Retrieval Sheet. AEs occurring more than 30 days after last study treatment exposure date are not summarized.


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Table 14.3.1-6.5.1 Treatment-emergent adverse events of interest incidence by specific group and preferred 
term during post-randomization consolidation phase (ARM 2) – overall and maximum grade 3/4 –
Subset of Full Analysis Set randomized to Arm 2
Specific group
   Preferred term
Arm 2
N=xx
All grades
n (%)
Grade 3/4
n (%)
All AESI
xx (xx.x)
xx (xx.x)
Group 1
PT 1
xx (xx.x)
xx (xx.x)
PT 2
xx (xx.x)
xx (xx.x)
ect..
xx (xx.x)
xx (xx.x)
Group 2
PT 1
xx (xx.x)
xx (xx.x)
PT 2
xx (xx.x)
xx (xx.x)
ect..
xx (xx.x)
xx (xx.x)
ect..
- Only treatment emergent adverse events from post-rand. cons. phase are included in this table.
- Specific groups are alphabetically presented; preferred terms are sorted within each group in descending 
frequency of ‘All grades’ column. Percentage based on the number of patients included in the analysis population (N).
- Treatment post-randomization Arm 2: 12 months, Re-treatment max Arm 2: 24 months. 
- A patient with multiple occurrences of an AE is counted only once in the AE category. A patient with multiple adverse 
events within a group is counted only once in the total row. AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and 
CVEs (others) are based on grouped MedDRA terms as described in the Case Retrieval Sheet. AEs occurring more than 30 days 
after last study treatment exposure date are not summarized.


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Table 14.3.1-6.5.2 Treatment-emergent adverse events of interest occurrence, by specific group and preferred 
term during post-randomization consolidation phase (ARM 2) – overall and maximum grade 3/4 –
Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-6.5.1   but without percentages, use footnotes:
- Only treatment emergent adverse events from post-rand. cons. phase are included in this table.
- Specific groups are alphabetically presented; preferred terms are sorted within each group in descending 
frequency of ‘All grades’ column.
- Treatment post-randomization Arm 2: 12 months, Re-treatment max Arm 2: 24 months. AE of special interest CVEs (IHD), CVEs 
(PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described in the Case Retrieval Sheet.
- AEs occurring more than 30 days after last study treatment exposure date are not summarized.


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Table 14.3.1-6.6.1 Treatment-emergent adverse events of interest incidence by specific group and preferred 
term during re-treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis Set entering 
the re-treatment phase
Specific group
   Preferred term
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
All grades
n (%)
Grade 3/4
n (%)
All grades
n (%)
Grade 3/4
n (%)
All grades
n (%)
Grade 3/4
n (%)
All AESI
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Group 1
PT 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
PT 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ect..
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Group 2
PT 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
PT 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ect..
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
ect..
- Only treatment emergent adverse events from re-treatment phase are included in this table.
- Specific groups are alphabetically presented; preferred terms are sorted within each group in descending 
frequency of ‘All grades’ column. Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- A patient with multiple occurrences of an AE is counted only once in the AE category. A patient with multiple adverse 
events within a group is counted only once in the total row. AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and 
CVEs (others) are based on grouped MedDRA terms as described in the Case Retrieval Sheet.AEs occurring more than 30 days 
after last study treatment exposure date are not summarized.


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Table 14.3.1-6.6.2 Treatment-emergent adverse events of interest occurrence by specific group and preferred 
term during re-treatment phase – overall and maximum grade 3/4 – Subset of Full Analysis Set entering 
the re-treatment phase
<< Programming note: Same shell as table 14.3.1-6.6.1 but without percentages, use footnotes: 
- Only treatment emergent adverse events from re-treatment phase are included in this table.
- Specific groups are alphabetically presented; preferred terms are sorted within each group in descending 
frequency of ‘All grades’ column.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described 
in the Case Retrieval Sheet. AEs occurring more than 30 days after last study treatment exposure date are not summarized. >>
Table 14.3.1-6.7.1 Adverse events of interest incidence by specific group and preferred term during TFR phase 
– overall and maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-6.6.1 for TFR, use footnotes:
- Only adverse events from TFR phase are included in this table.
- Specific groups are alphabetically presented; preferred terms are sorted within each group in descending 
frequency of ‘All grades’ column. Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- A patient with multiple occurrences of an AE is counted only once in the AE category. A patient with multiple AE within a 
primary system organ class is counted only once in the total row. AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) 
and CVEs (others) are based on grouped MedDRA terms as described in the Case Retrieval Sheet. >>
Table 14.3.1-6.7.2 Adverse events of interest occurrence by specific group and preferred term during TFR 
phase – overall and maximum grade 3/4 – Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-6.7.1 but without percentages use footnotes:
- Only adverse events from TFR phase are included in this table.
- Specific groups are alphabetically presented; preferred terms are sorted within each group in descending 
frequency of ‘All grades’ column.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. 
- AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described 
in the Case Retrieval Sheet.


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Table 14.3.1-7.1.1 Treatment Emergent adverse events of interest incidence, regardless of study drug 
relationship, by specific group and preferred term and by cardiovascular risk factors during Pre-
randomization Induction/consolidation phase – by treatment arm, overall and maximum grade 3/4 –
Full Analysis Set
Very high or high risk / Moderate or low risk 
Arm 1
N=xxx
Arm 2
N=xxx
Randomized
N=xxx
Not Randomized
N=xxx
Total
N=xxx
Specific group 
Preferred term
All grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All AESI
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Group 1
PT1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
PT2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
Group 2
PT1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
PT2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
- Only TEAEs from pre-rand. ind./cons. phase are included in this table. Specific groups are presented alphabetically; 
- PTs are sorted within each group in descending frequency of ‘All grades’ column.
- Percentage based on the population number (N). Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 
36/24 months. 
A patient with multiple occurrences of an AE is counted only once in the AE category.
- A patient with multiple AEs within a group is counted only once in the total row. AE of special interest CVEs (IHD), 
CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described in the Case Retrieval Sheet.
- CV risk factors are defined as described in EU Guidelines on cardiovascular disease prevention in clin. Practice
(version 2012). European Heart Journal (2012) 33, 1635–1701. AEs occurring more than 30 days after last study treatment 
exposure date are not summarized.


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Table 14.3.1-7.1.2 Treatment Emergent adverse events of interest occurrence, regardless of study drug 
relationship, by specific group and preferred term and by cardiovascular risk factors during Pre-
randomization Induction/consolidation phase – by treatment arm, overall and maximum grade 3/4 –
Full Analysis Set 
<< Programming note:
Same shell as table 14.3.1-7.1.1   but without percentages use footnotes:
- Only TEAEs from pre-rand. ind./cons. phase are included in this table. Specific groups are presented alphabetically; 
- PTs are sorted within each group in descending frequency of ‘All grades’ column.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 
36/24 months. AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped 
MedDRA terms as described in the Case Retrieval Sheet.
- CV risk factors are defined as described in EU Guidelines on cardiovascular disease prevention in clinical 
practice (version 2012). European Heart Journal (2012) 33, 1635–1701. AEs occurring more than 30 days after 
last study treatment exposure date are not summarized.


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Table 14.3.1-7.2.1 Treatment-emergent adverse events of interest incidence, regardless of study drug 
relationship, during post-randomization consolidation phase (ARM 2), by specific group and preferred 
term, and by cardiovascular risk factor– overall and maximum grade 3 or 4 – Subset of Full Analysis 
Set randomized to Arm 2
Subgroup: Cardiovascular risk factor at baseline: Very high/High risk 
(Note for programming: to be repeated on Moderate/Low risk)
Specific group
   Preferred term
Arm 2
N=xx
All grades
n (%)
Grade 3/4
n (%)
All AESI
xx (xx.x)
xx (xx.x)
Group 1
PT 1
xx (xx.x)
xx (xx.x)
PT 2
xx (xx.x)
xx (xx.x)
ect..
xx (xx.x)
xx (xx.x)
Group 2
PT 1
xx (xx.x)
xx (xx.x)
PT 2
xx (xx.x)
xx (xx.x)
ect..
xx (xx.x)
xx (xx.x)
ect..
- Only TEAEs from post-rand. cons. phase are included in this table. Specific groups are presented alphabetically;
- PTs are sorted within each group in descending frequency of ‘All grades’ column. Percentage based on the population 
number (N). Treatment post-randomization Arm 2: 12 months, Re-treatment max Arm 2: 24 months. A patient with multiple 
occurrences of an AE is counted only once in the AE category. A patient with multiple AEs within a group is counted 
only once in the total row. AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based 
on grouped MedDRA terms as described in the Case Retrieval Sheet. CV risk factors are defined as described in EU Guidelines 
on cardiovascular disease prevention in clin. practice (version 2012). European Heart Journal (2012) 33,
1635–1701. AEs occurring more than 30 days after last study treatment exposure date are not summarized.


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<< Note for programming:
The “N” in header should correspond to the number of patient in the analysis set and in the selected cardiovascular risk factor 
subgroup.
When there is no AE in the selected subgroup, please indicate 0 for the row below:
All AESI
xx (xx.x)
xx (xx.x)
When there is no patient in the analysis set and subgroup selected then do not display the subgroup.>>
Table 14.3.1-7.2.2 Treatment-emergent adverse events of interest occurrence, regardless of study drug 
relationship, during post-randomization consolidation phase (ARM 2), by specific group and preferred 
term, and by cardiovascular risk factor – overall and maximum grade 3 or 4 – Subset of Full Analysis 
Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-7.2.1  but without percentages use footnotes:
- Only TEAEs from post-rand. cons. phase are included in this table. Specific groups are presented alphabetically; 
PTs are sorted within each group in descending frequency of ‘All grades’ column.
- Treatment post-randomization Arm 2: 12 months, Re-treatment max Arm 2:
24 months. AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as 
described in the Case Retrieval Sheet.
- CV risk factors are defined as described in EU Guidelines on cardiovascular disease prevention in clin. practice (version 
2012). European Heart Journal (2012) 33, 1635–1701. AEs occurring more than 30 days after last study treatment 
exposure date are not summarized.


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Table 14.3.1-7.3.1 Treatment-emergent adverse events of interest incidence, regardless of study drug 
relationship, during re-treatment phase, by specific group and preferred term, and by cardiovascular 
risk factor – Subset of Full Analysis Set entering the re-treatment phase
Very high or high risk / Moderate or low risk 
Arm 1
N=xxx
Arm 2
N=xxx
Total
N=xxx
Specific group 
Preferred term
All grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All 
grades 
n (%)
Grade
3/4  
n (%)
All AESI
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Group 1
PT1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
PT2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
Group 2
PT1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
PT2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
- Only TEAEs from re-treatment phase are included in this table. Specific groups are presented alphabetically;
- PTs are sorted within each group in descending frequency of ‘All grades’ column.
- Percentage based on the population number (N). Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 
36/24 months. A patient with multiple occurrences of an AE is counted only once in the AE category. A patient
with multiple AEs within a group is counted only once in the total row. AE of special interest CVEs (IHD), 
CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described in the Case Retrieval Sheet.
- CV risk factors are defined as described in EU Guidelines on cardiovascular disease prevention in clin. practice 
(version 2012). European Heart Journal (2012) 33, 1635–1701. AEs occurring more than 30 days after last study treatment 
exposure date are not summarized.


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Table 14.3.1-7.3.2 Treatment-emergent adverse events of interest occurrence, regardless of study drug 
relationship, during re-treatment phase, by specific group and preferred term, and by cardiovascular 
risk factor – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-7.3.1 but without percentages use footnotes:
- Only TEAEs from re-treatment phase are included in this table. Specific groups are presented alphabetically; 
- PTs are sorted within each group in descending frequency of ‘All grades’ column.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. AE of special interest CVEs (IHD), 
CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described in the Case Retrieval Sheet. 
- CV risk factors are defined as described in EU Guidelines on cardiovascular disease prevention in clin. practice
(version 2012). European Heart Journal (2012) 33, 1635–1701. AEs occurring more than 30 days after last study treatment 
exposure date are not summarized.


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Table 14.3.1-7.4.1 Adverse events of interest incidence, regardless of study drug relationship, during TFR 
phase, by specific group and preferred term, and by cardiovascular risk factor – Subset of Full Analysis 
Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-7.3.1 for TFR, use footnotes:
- Only AEs from TFR phase are included in this table. Specific groups are presented alphabetically; 
- PTs are sorted within each group in descending frequency of ‘All grades’ column.
- Percentage based on the population number (N). Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2:
36/24 months. A patient with multiple occurrences of an AE is counted only once in the AE category. A patient 
with multiple AEs within a group is counted only once in the total row. AE of special interest CVEs (IHD),
CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms as described in the Case Retrieval Sheet.
- CV risk factors are defined as described in EU on cardiovascular disease prevention in clin. practice (version 2012). 
European Heart Journal (2012) 33, 1635–1701. >>
Table 14.3.1-7.4.2 Adverse events of interest occurrence, regardless of study drug relationship, during TFR
phase, by specific group and preferred term, and by cardiovascular risk factor – Subset of Full Analysis 
Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-7.4.1 but without percentages, use footnotes:
- Only AEs from TFR phase are included in this table. Specific groups are presented alphabetically;
- PTs are sorted within each group in descending frequency of ‘All grades’ column. 
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 
36/24 months. AE of special interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped 
MedDRA terms as described in the Case Retrieval Sheet. CV risk factors are defined as described in EU Guidelines on 
cardiovascular disease prevention in clin. practice (version 2012). European Heart Journal (2012) 33, 1635–1701.>>


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Table 14.3.1-7.5.1 Treatment-emergent adverse events of interest incidence, regardless of study drug 
relationship, during pre-randomization Induction/consolidation phase, by specific group and preferred 
term and by 4 cardiovascular risk factors – overall and maximum grade 3/4  –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-7.1.1 but using:  Very high risk, High risk, Moderate risk, Low risk>>
Table 14.3.1-7.5.2 Treatment-emergent adverse events of interest occurence, regardless of study drug 
relationship, during pre-randomization Induction/consolidation phase, by specific group and preferred 
term and by 4 cardiovascular risk factors – overall and maximum grade 3/4 –Full Analysis Set 
<< Programming note: Same shell as table 14.3.1-7.1.2 but using:  Very high risk, High risk, Moderate risk, Low risk>>
Table 14.3.1-7.6.1 Treatment-emergent adverse events of interest incidence, regardless of study drug 
relationship, during post-randomization consolidation phase (ARM 2), by specific group and preferred 
term, and by 4 categories of cardiovascular risk factors– overall and maximum grade 3 or 4 – Subset 
of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-7.2.1 but using:  Very high risk, High risk, Moderate risk, Low risk>>
Table 14.3.1-7.6.2 Treatment-emergent adverse events of interest occurrence, regardless of study drug 
relationship, during post-randomization consolidation phase (ARM 2), by specific group and preferred 
term, and by 4 categories of cardiovascular risk factors – overall and maximum grade 3 or 4 – Subset 
of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-7.2.2 but using:  Very high risk, High risk, Moderate risk, Low risk>>


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Table 14.3.1-7.7.1 Treatment-emergent adverse events of interest incidence, regardless of study drug 
relationship, during re-treatment phase, by specific group and preferred term, and by 4 categories of 
cardiovascular risk factors – Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-7.3.1 but using:  Very high risk, High risk, Moderate risk, Low risk>>
Table 14.3.1-7.7.2 Treatment-emergent adverse events of interest occurrence, regardless of study drug 
relationship, during re-treatment phase, by specific group and preferred term, and by 4 categories of 
cardiovascular risk factors– Subset of Full Analysis Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-7.3.2 but using:  Very high risk, High risk, Moderate risk, Low risk>>


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Table 14.3.1-7.8.1 Adverse events of interest incidence, regardless of study drug relationship, during TFR 
phase, by specific group and preferred term, and by 4 categories of cardiovascular risk factors –
Subset of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-7.4.1 but using:  Very high risk, High risk, Moderate risk, Low risk>>
Table 14.3.1-7.8.2 Adverse events of interest occurrence, regardless of study drug relationship, during TFR 
phase, by specific group and preferred term, and by 4 categories of cardiovascular risk factors– Subset 
of Full Analysis Set entering the TFR phase
<< Programming note: Same shell as table 14.3.1-7.4.2 but using:  Very high risk, High risk, Moderate risk, Low risk>>


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Table 14.3.1-9.1 On treatment deaths, by system organ class and preferred term during pre-randomization 
Induction/Consolidation phase - Safety Set
Primary system organ class
Principal cause of death
Arm 1
N=xxx
n (%)
Arm 2
N=xxx
n (%)
Randomized
N=xxx
n (%)
Not Randomized
N=xxx
n (%)
Total
N=xxx
n (%)
Any Primary system organ class
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Primary system organ class 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Preferred term 1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  Preferred term 2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
       ...
...
...
...
...
...
                                                                         
- Primary system organ classes are alphabetically presented; preferred terms are sorted within primary system organ class in  
descending frequency.
- Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months.
- Deaths up to 30 days after last study treatment exposure date are all included 
- For patient #
, date of death was imputed to “
”, from the original “
” for the purpose of 
this table only. 
<<Programming note: Include all deaths recorded on the AE CRF page>>


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Table 14.3.1-9.2 On treatment deaths, by system organ class and preferred term during post-randomization 
consolidation phase (ARM 2) – Subset of Safety Set randomized to Arm 2
Primary system organ class
Principal cause of death
Arm 2
N=xxx
n (%)
Any Primary system organ class
xx (xx.x)
Primary system organ class 1
xx (xx.x)
  Preferred term 1
xx (xx.x)
  Preferred term 2
xx (xx.x)
       ...
...
                                                                         
- Primary system organ classes are alphabetically presented; preferred terms are sorted within primary system organ class in  
descending frequency.
- Percentage based on the number of patients included in the analysis population (N).
- Treatment post-randomization Arm 2: 12 months, Re-treatment max Arm 2: 24 months. 
- Deaths up to 30 days after last study treatment exposure date are all included 
<<Programming note: Include all deaths recorded on the AE CRF page>>
Table 14.3.1-9.3 On treatment deaths, by system organ class and preferred term during re-treatment phase –
Subset of Safety Set entering the re-treatment phase
<< Programming note: Same shell as table 14.3.1-9.1 presenting only Arm 1, Arm 2 and Total, use footnotes:>
Primary system organ classes are alphabetically presented; preferred terms are sorted within primary system organ class in  
descending frequency.
- Only deaths occurring during the treatment period (between the first day of study drug intake and up to 30 days after last 
study drug intake) are presented. 
- Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months.


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Table 14.3.1-10.1.1 Cardiac and vascular adverse events of interest, incidence, by treatment arm during the 
pre-randomization induction/consolidation phase - Full Analysis Set
Arm 1
N=xxx
Arm 1
N=xxx
Randomized
N=xxx
Not Randomized
N=xxx
Total
N=xxx
Cardiac and vascular 
adverse events
All 
grades
n  (%)
Grade 
3/4
n  (%)
All 
grades
n  (%)
Grade 
3/4
n  (%)
All 
grades
n  (%)
Grade 3/4
n  (%)
All 
grades
n  (%)
Grade 
3/4
n  (%)
All 
grades
n  (%)
Grade 
3/4
n  (%)
Any cardiac event
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any serious cardiac event
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any cardiac event related 
to study treatment
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any cardiac event leading 
to study drug 
discontinuation
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any vascular event
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any serious vascular 
event
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any vascular event 
related to study 
treatment
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Any vascular event 
leading to study drug 
discontinuation
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Number of cardiac events 
per patient
0 time
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
1 time
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx


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2 times
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
3 times
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
4 or more times
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
Number of vascular events 
per patient
0 time
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
1 time
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
2 times
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
3 times
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
4 or more times
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
                                                                           
  
- Only pre-randomization events occurring during induction/consolidation or within 30 days after the last study treatment 
exposure (pre-randomization consolidation period 12-24 months) date are displayed. Percentage based on the number of patients 
included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. A patient with multiple occurrences of an 
event is counted only once. Events of interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped 
MedDRA terms from the Case Retrieval Sheet. Cardiac events correspond to events of interest with System Organ Class “Cardiac 
disorders” and vascular events correspond to events of interest with System Organ Class “Vascular disorders”.
<<Programming note: Only adverse events of special interest are displayed, there are defined with case retrieval sheet where 
compound are: CVES(IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) (AEVSG not empty in A_AEV dataset and SOC= Cardiac 
disorders or Vascular disorders). If date of start of AE ≤ Day 365 then AE will be count in induction phase, else if date of 
start of AE > Day 365 then it will be considered in consolidation phase. >>


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Table 14.3.1-10.1.2 Cardiac and vascular adverse events of interest, occurence, by treatment arm during the 
pre-randomization induction/consolidation phase - Full Analysis Set
<< Programming note: Same shell as table 14.3.1-10.1.1 but without percentages, use footnotes:
- Only pre-randomization events occurring during induction/consolidation or within 30 days after the last study treatment 
exposure (pre-randomization consolidation period 12-24 months) date are displayed.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. Events of interest CVEs (IHD), CVEs 
(PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms from the Case Retrieval Sheet. Cardiac events 
correspond to events of interest with System Organ Class “Cardiac disorders” and vascular events correspond to events of 
interest with System Organ Class “Vascular disorders”.


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Table 14.3.1-10.2.1 Cardiac and vascular adverse events of interest incidence, during the post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to Arm 2
Arm 2
N=xxx
Cardiac and vascular 
adverse events
All 
grades
n  (%)
Grade 
3/4
n  (%)
Any cardiac event
xx (xx.x)
xx (xx.x)
Any serious cardiac event
xx (xx.x)
xx (xx.x)
Any cardiac event related to study treatment
xx (xx.x)
xx (xx.x)
Any cardiac event leading to study drug discontinuation
xx (xx.x)
xx (xx.x)
Any vascular event
xx (xx.x)
xx (xx.x)
Any serious vascular event
xx (xx.x)
xx (xx.x)
Any vascular event related to study treatment
xx (xx.x)
xx (xx.x)
Any vascular event leading to study drug discontinuation
xx (xx.x)
xx (xx.x)
Number of cardiac events per patient
0 time
xx
xx
1 time
xx
xx
2 times
xx
xx
3 times
xx
xx
4 or more times
xx
xx
Number of vascular events per patient
0 time
xx
xx


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1 time
xx
xx
2 times
xx
xx
3 times
xx
xx
4 or more times
xx
xx
                                                                           
  
- Only events occurring during post-randomization or within 30 days after the last study treatment exposure (post-
randomization consolidation period 12 months) date are displayed. Percentage based on the number of patients included in the 
analysis population (N).
- Treatment post-randomization Arm 2: 12 months. A patient with multiple occurrences of an event is counted only once. Events 
of interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms from the Case Retrieval 
Sheet. Cardiac events correspond to events of interest with System Organ Class “Cardiac disorders” and vascular events 
correspond to events of interest with System Organ Class “Vascular disorders”.
Table 14.3.1-10.2.2 Cardiac and vascular adverse events of interest occurrence, during the post-randomization 
consolidation phase (ARM 2) - Subset of Full Analysis Set randomized to Arm 2
<< Programming note: Same shell as table 14.3.1-10.2.1 but without percentages, use footnotes:
- Only events occurring during post-randomization or within 30 days after the last study treatment exposure (post-
randomization consolidation period 12 months) date are displayed. 
- Treatment post-randomization Arm 2: 12 months. Events of interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are 
based on grouped MedDRA terms from the Case Retrieval Sheet. Cardiac events correspond to events of interest with System 
Organ Class “Cardiac disorders” and vascular events correspond to events of interest with System Organ Class “Vascular 
disorders”.
Table 14.3.1-10.3.1 Cardiac and vascular adverse events of interest, incidence, by treatment arm during the re-
treatment phase – Subset of Full Analysis Set entered re-treatment phase
<< Programming note: Same shell as table 14.3.1-10.1.1 but for re-treatment, use footnotes: 
- Only events occurring during re-treatment phase or within 30 days after the last study treatment exposure (re-treatment 
period 24-36 months) date are displayed. Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. A patient with multiple occurrences of an 
event is counted only once. Events of interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped 
MedDRA terms from the Case Retrieval Sheet. Cardiac events correspond to events of interest with System Organ Class “Cardiac 
disorders” and vascular events correspond to events of interest with System Organ Class “Vascular disorders”.


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Table 14.3.1-10.3.2 Cardiac and vascular adverse events of interest, occurence, by treatment arm during the 
re-treatment phase - Subset of Full Analysis Set entered re-treatment phase
<< Programming note: Same shell as table 14.3.1-10.3.1 but without percentages, using footnotes:
- Only events occurring during re-treatment phase or within 30 days after the last study treatment exposure (re-treatment 
period 24-36 months) date are displayed. 
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months. Events of interest CVEs (IHD), CVEs 
(PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms from the Case Retrieval Sheet. Cardiac events 
correspond to events of interest with System Organ Class “Cardiac disorders” and vascular events correspond to events of 
interest with System Organ Class “Vascular disorders”.


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Table 14.3.1-10.4.1 Cardiac and vascular adverse events of interest, incidence, by treatment arm during the 
TFR phase – Subset of Full Analysis Set entered TFR phase
<< Programming note: Same shell as table 14.3.1-10.1.1 but for TFR use footnotes:
- Only events occurring during TFR phase (TFR period 24-36 months) date are displayed.
- Percentage based on the number of patients included in the analysis population (N).
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months.
- A patient with multiple occurrences of an event is counted only once.
- Events of interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms from the Case 
Retrieval Sheet. Cardiac events correspond to events of interest with System Organ Class “Cardiac disorders” and vascular 
events correspond to events of interest with System Organ Class “Vascular disorders”.>>
Table 14.3.1-10.4.2 Cardiac and vascular adverse events of interest, occurence, by treatment arm during the 
TFR phase - Subset of Full Analysis Set entered TFR phase
<< Programming note: Same shell as table 14.3.1-10.4.1 but without percentages use footnotes:
- Only events occurring during TFR phase (TFR period 24-36 months) date are displayed.
- Treatment Arm 1/Arm 2: 24/36 months, Re-treatment max Arm 1/Arm 2: 36/24 months.
- Events of interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based on grouped MedDRA terms from the Case 
Retrieval Sheet. Cardiac events correspond to events of interest with System Organ Class “Cardiac disorders” and vascular 
events correspond to events of interest with System Organ Class “Vascular disorders”.>>


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Table 14.3.1-10.5 Relationship between cardiac and vascular adverse events of interest with total cholesterol 
values - Full Analysis Set
Total Cholesterol Values
Adverse events
<=  5.2 mmol/L
>5.2 and <=6.2 mmol/L
> 6.2 mmol/L
Missing
Cardiac events
Yes
xx
xx
xx
xx
No
xx
xx
xx
xx
Vascular events
Yes
xx
xx
xx
xx
No
xx
xx
xx
xx
- All events are considered, even if occurred on same patient. All AEs occurring during the study or 
within 30 days after the last study treatment exposure date are displayed. For patients with event, 
the last laboratory available assessment before or at date of start of the event is considered.
When the date of the AE is missing, the first laboratory assessment after the start of the study med.
is considered. Patients without event are counted only once, presented under the highest total 
cholesterol value.  Events of interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based
on grouped MedDRA terms from the Case Retrieval Sheet. Cardiac events correspond to events of interest
with SOC “Cardiac disorders” and vascular events correspond to events of interest with SOC “Vascular disorders”.
<<Programming note: Only adverse events of special interest are displayed, there are defined with case retrieval sheet where 
compound are: CVES(IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) (AEVSG not empty in A_AEV dataset and SOC= Cardiac 
disorders or Vascular disorders).
Patient with no event of interest should be counted in category NO of highest value post-baseline or in category Missing 
otherwise.>>


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Table 14.3.1-10.6 Relationship between cardiac and vascular adverse events of interest with glycemic values -
Full Analysis Set
Fasting Glucose Values
Adverse events
≤6.9 mmol/L
> 6.9 mmol/L
Missing
Cardiac events
Yes
xx
xx
xx
No
xx
xx
xx
Vascular events
Yes
xx
xx
xx
No
xx
xx
xx
- All events are considered, even if occurred on same patient. All AEs during the study or 
within 30 days after the last study treatment exposure date are displayed. For patients with event,
the last laboratory available assessment before or at date of start of the first event is considered.
When the date of the AE is missing, the first laboratory assessment after the start of the study med.
is considered. Patients without event are counted only once, presented under the highest fasting 
glucose value.  Events of interest CVEs (IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) are based
on grouped MedDRA terms from the Case Retrieval Sheet. Cardiac events correspond to events of interest
with SOC “Cardiac disorders” and vascular events correspond to events of interest with SOC “Vascular disorders”.                       
<<Programming note: Only adverse events of special interest are displayed, there are defined with case retrieval sheet where 
compound are: CVES(IHD), CVEs (PAOD), CVEs (ICD) and CVEs (others) (AEVSG not empty in A_AEV dataset and SOC= Cardiac 
disorders or Vascular disorders).>>


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Table 14.3.1-11.1.1 Kaplan-Meier estimate of time-to-first CVEs during the pre-randomization
induction/consolidation phase – Full analysis set
                                        
KM estimates
Arm 1
N=xx
Arm 2
N=xx
Randomized
N=xx
  Not 
Randomized
N=xx
Total
N=xx
Number of patients - n (%)
with
events
xxx (xx.x)
xxx (xx.x)
...
...
xxx (xx.x)
with
censorings 
xxx (xx.x)
xxx (xx.x)
...
...
xxx (xx.x)
Time to event (months)
25th percentile (95% CI)
xx.x (xx.x, xx.x)
xx.x (xx.x, xx.x)
...
...
xx.x (xx.x, xx.x)
Median (95% CI)
xx.x (xx.x, xx.x)
xx.x (xx.x, xx.x)
...
...
xx.x (xx.x, xx.x)
75th percentile (95% CI)
xx.x (xx.x, xx.x)
xx.x (xx.x, xx.x)
...
...
xx.x (xx.x, xx.x)
Percentage of patients 
without event –
Estimate (95% CI) 
6 months
xx.x (xx.x) (xx.x, xx.x)
xx.x(xx.x)  (xx.x, xx.x)
...
...
xx.x(xx.x)  (xx.x, xx.x)
12 months
xx.x (xx.x) xx.x, xx.x)
xx.x(xx.x)  (xx.x, xx.x)
...
...
xx.x(xx.x)  (xx.x, xx.x)
18 months
xx.x (xx.x) (xx.x, xx.x)
xx.x(xx.x)  (xx.x, xx.x)
...
...
xx.x(xx.x)  (xx.x, xx.x)
24 months
xx.x (xx.x) (xx.x, xx.x)
xx.x(xx.x)  (xx.x, xx.x)
...
...
xx.x(xx.x)  (xx.x, xx.x)
- NE: Not Estimable.
- Event = first occurrence of CVE during the pre-randomization induction/consolidation phase.
- Censoring rule = patients who did not meet the event are censored to the minimum date between the last contact 
date, the end of induction/consolidation phase, the randomization date the date of death.
- n is the number of patients at risk at the timepoint (i.e. without event and still ongoing)
- The percentage of patients without event and the respective 95% C.I. are estimated from Kaplan Meier.
- Presenting CVEs occurred within Pre-Randomization Ind/Cons phase only, excluding additional +30 days period used in TEAE 
outputs.
<< Programming note: The procedure to be used is described below:


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proc lifetest data=data outsurv=surv stderr method=km atrisk;
  time VART*evt(0) ;
  strata TRT;
    ods output
    Quartiles =Quartile
    ProductLimitEstimates=lifetable
    censoredsummary=Censum(keep=TRT stratum failed total censored);
run;
*Frame for all time points (please use maximum time as required. As an example here I am using 1-50);
data frame;
  do TRT= 1 to 2;
   do VART= 1 to 50 by 1;
output;
   end;
  end;
run;
proc sort data=frame ; by TRT VART; run;
proc sort data=surv ; by TRT VART; run;
data surv1;
  merge surv(in=a) frame(in=b);
  if a or b;
  by TRT VART; 
run;
********Using LOCF to impute all records with valid results *******;
data surv2;
   set surv1;
   retain psurv up low ;
   by TRT;
   if first.TRT then psurv=.;
   if survival ne . then psurv=survival;
   if first.TRT then up=.;
   if sdf_ucl ne . then up=sdf_ucl;
   if first.TRT then low=.;
   if sdf_lcl ne . then low=sdf_lcl;
run;
*Keep only 1 row per time point per treatment arm. Find specific timepoint;


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proc sort data=surv2 out=surv3 nodupkey; by  TRT VART; run;
*Quartile and Censum contain the information for the first two parts of the table;


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Table 14.3.1-11.1.2 Kaplan-Meier estimate of time-to-first CVEs during the post-randomization consolidation 
phase (ARM 2)– Subset of Full Analysis Set patients randomized on Arm 2
                                                                                                       
KM estimates
Arm2
N=xx
Number of patients - n (%)
with events
xxx (xx.x)
with censorings
xxx (xx.x)
Time to event (months)
25th percentile (95% CI)
xx.x (xx.x, xx.x)
Median (95% CI)
xx.x (xx.x, xx.x)
75th percentile (95% CI)
xx.x (xx.x, xx.x)
Percentage of patients without event –
Estimate n(%) (95% CI) 
6 months
xx.x (xx.x) (xx.x, xx.x)
12 months
xx.x(xx.x) (xx.x, xx.x)
- NE: Not Estimable.
- Event = first occurrence of CVE during the post-randomization induction/consolidation phase.
- Censoring rule = patients who did not meet the event are censored to the minimum date between the last contact
date, the end of induction/consolidation phase and the date of death.
- n is the number of patients at risk at the timepoint (i.e. without event and still ongoing)
- The percentage of patients without event and the respective 95% C.I. are estimated from Kaplan Meier.
- Patients randomized to Arm 2 have 12 months of treatment post-randomization and a maximum of 24 months of re-treatment.
- Presenting CVEs occurred within Post-Randomization consolidation phase only, excluding additional +30 days period used in 
TEAE outputs.


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Table 14.3.1-11.2 Kaplan-Meier estimate of time-to-first CVEs during the re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase
KM estimates
Arm 1
N=xx
Arm 2
N=xx
Total
N=xx
Number of patients - n (%)
with events
xxx (xx.x)
xxx (xx.x)
xxx (xx.x)
with censorings 
xxx (xx.x)
xxx (xx.x)
xxx (xx.x)
Time to event (months)
25th percentile (95% CI)
xx.x (xx.x, xx.x)
xx.x (xx.x, xx.x)
xx.x (xx.x, xx.x)
Median (95% CI)
xx.x (xx.x, xx.x)
xx.x (xx.x, xx.x)
xx.x (xx.x, xx.x)
75th percentile (95% CI)
xx.x (xx.x, xx.x)
xx.x (xx.x, xx.x)
xx.x (xx.x, xx.x)
Percentage of patients without event –
Estimate n(%) (95% CI) 
6 months
xx.x (xx.x) (xx.x, xx.x)
xx.x (xx.x) (xx.x, xx.x)
xx.x (xx.x) (xx.x, xx.x)
12 months
xx.x (xx.x) (xx.x, xx.x)
xx.x (xx.x) (xx.x, xx.x)
xx.x (xx.x) (xx.x, xx.x)
24 months
xx.x (xx.x) (xx.x, xx.x)
xx.x (xx.x) (xx.x, xx.x)
xx.x (xx.x) (xx.x, xx.x)
30 months
xx.x (xx.x) (xx.x, xx.x)
xx.x (xx.x) (xx.x, xx.x)
36 months
xx.x (xx.x) (xx.x, xx.x)
xx.x (xx.x) (xx.x, xx.x)
   -
NE: Not Estimable.
   -
Event = first occurrence of CVE during the re-treatment phase.
   -  Censoring rule = patients who did not meet the event are censored to the minimum date between the last contact
     date, the end of re-treatment phase and the date of death.
- n is the number of patients at risk at the timepoint (i.e. without event and still ongoing)
- The percentage of patients without event and the respective 95% C.I. are estimated from Kaplan Meier.
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
  - Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
- Presenting CVEs occurred within Re-treatment phase only, excluding additional +30 days period used in TEAE outputs.
<< Programming note: Time to start date is the first day of re-treatment phase.>>


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Table 14.3.1-12.1 Medical history by system organ class and preferred term- Full Analysis Set
System organ class 
Preferred term
Arm 1
N=xxx
n(%)
Arm 2
N=xxx
n(%)
Randomized
N=xxx
n(%)
Not Randomized
N=xxx
n(%)
Total
N=xxx
n(%)
SOC1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  PT1 
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  PT2 
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
...
...
...
...
...
SOC2
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
...
...
...
...
...
...
- Primary system organ classes are presented alphabetically; preferred terms are sorted within Primary system organ class by
descending frequency.


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Table 14.3.1-13.1 Prior exposure to imatinib before screening, MMR, age, and Sokal by LSC detection category 
- LSC sub-study Full Analysis Set
- LSC detected defined as Ph+ CD34/38+, or CD34/CD38–, or Immunophenotypically aberrant CD34+, or Immunophenotypically 
aberrant CD34-, for HIS, or PCR, or both.
# Baseline value, latest available valid evaluation between Screening and Rescreening.
Programming Note: Separate denominator for each column. Percentages sum up to 100% for each column/variable.
Baseline#
LSC detected
n(%)
LSC not detected
n(%)
Not 
Randomized
N=XX
Randomized 
(Arm 1 and Arm 2)
N=XX
Not
Randomized
N=XX
Randomized 
(Arm 1 and Arm 2)
N=XX
Prior Imatinib exposure
<5 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 5 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
MMR
Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
No
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Age
<65 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
>= 65 years
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Sokal score
Low risk
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Intermediate risk
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
High risk
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)


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Protocol No CAMN107AIC0
Table 14.3.1-13.2.1 Percentage from total CD34+ cells, CD34+/CD38+ cells - Subgroup of LSC sub-study Full 
Analysis Set, LSC detected
LSC 
cells
Arm 1
(N=xx)
Arm 2
(N=xx)
Randomized
(Arm 1 and 
Arm 2)
(N=xx)
Not Randomized
(N=xx)
Total
(Randomized and 
Not Randomized)
(N=xx)
Baseline#
n
xxx
xxx
xxx
xxx
xxx
Mean
xx.x
xx.x
xx.x
xx.x
xx.x
SD
x.xx
x.xx
x.xx
x.xx
x.xx
25th percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
xx.x
xx.x
75th percentile
xx.x
xx.x
xx.x
xx.x
xx.x
Min, Max
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
Month 24
n
xxx
xxx
xxx
xxx
xxx
...
...
...
...
...
...
Min, Max
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
Change from Baseline 
to Month 24
n
xxx
xxx
xxx
xxx
xxx
...
...
...
...
...
...
Min, Max
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
Month 36*
n
xxx
xxx
xxx
xxx
xxx
...
...
...
...
...
...
Min, Max
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
Change from Baseline 
to Month 36*
n
xxx
xxx
...
...
...
Min, Max
xx.x, xx.x
xx.x, xx.x


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Protocol No CAMN107AIC0
EoP TFR
n
xxx
xxx
xxx
xxx
...
...
...
...
...
Min, Max
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
Change from Baseline 
to EoP TFR
n
xxx
xxx
xxx
xxx
...
...
...
...
...
Min, Max
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
xx.x, xx.x
- LSC detected defined as Ph+ CD34/38+, or CD34/CD38–, or Immunophenotypically aberrant CD34+, or Immunophenotypically 
aberrant CD34-, for HIS, or PCR, or both.                                    
# Baseline value, latest available valid evaluation between Screening and Rescreening.                             
* For subjects randomized to Arm 2.                                                                                
Table 14.3.1-13.2.2 Percentage from total CD34+ cells, CD34+/CD38- cells - Subgroup of LSC sub-study Full 
Analysis Set, LSC detected
<< Programming note: Same shell as Table 14.3.1-13.2.1 >>
Table 14.3.1-13.2.3 Percentage from total CD34+ cells, Immunophenotypically aberrant CD34+ cells - Subgroup 
of LSC sub-study Full Analysis Set, LSC detected
<< Programming note: Same shell as Table 14.3.1-13.2.1 >>


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Protocol No CAMN107AIC0
Table 14.3.1-13.2.4 Percentage from total CD34+ cells, Immunophenotypically aberrant CD34 negative cells -
Subgroup of LSC sub-study Full Analysis Set, LSC detected
<< Programming note: Same shell as Table 14.3.1-13.2.1>>
Table 14.3.1-13.3.1 Percentage of Ph+ cells, CD34+/CD38- cells - Subgroup of LSC sub-study Full Analysis Set, 
LSC detected
<< Programming note: Same shell as Table 14.3.1-13.2.1>>
Table 14.3.1-13.3.2 Percentage of Ph+ cells, CD34+/CD38- cells - Subgroup of LSC sub-study Full Analysis Set, 
LSC detected
<< Programming note: Same shell as Table 14.3.1-13.2.1>>
Table 14.3.1-13.3.3 Percentage of Ph+ cells, Immunophenotypically aberrant CD34+ cells - Subgroup of LSC 
sub-study Full Analysis Set, LSC detected
<< Programming note: Same shell as Table 14.3.1-13.2.1>>
Table 14.3.1-13.3.4 Percentage of Ph+ cells, Immunophenotypically aberrant CD34 negative cells - Subgroup 
of LSC sub-study Full Analysis Set, LSC detected
<< Programming note: Same shell as Table 14.3.1-13.2.1>>
Table 14.3.1-13.4 Total Percentage of CD34+ cells- Subgroup of LSC sub-study Full Analysis Set, LSC detected
<< Programming note: Same shell as Table 14.3.1-13.2.1>>


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Protocol No CAMN107AIC0
Table 14.3.1-13.5 LSC detection - LSC sub-study Full Analysis Set
LSC 
detected
Arm 1
(N=xx)
n(%)
Arm 2
(N=xx)
n(%)
Randomized
(Arm 1 and 
Arm 2)
(N=xx)
n(%)
Not Randomized
(N=xx)
n(%)
Total
(Randomized and 
Not Randomized)
(N=xx)
n(%)
Baseline#
Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
No
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Month 24
Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
No
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Month 36*
Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
No
xx (xx.x)
xx (xx.x)
xx (xx.x)
Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
EoP TFR
Yes
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
No
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Missing
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
  - LSC detected defined as Ph+ CD34/38+, or CD34/CD38–, or Immunophenotypically aberrant CD34+, or Immunophenotypically 
aberrant CD34-, for HIS, or PCR, or both.
  # Baseline value, latest available valid evaluation between Screening and Rescreening.
  *For subjects randomized to Arm 2.


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Protocol No CAMN107AIC0
Section 14.3.2 – Listings of deaths, other serious and significant adverse events
Listing 14.3.2-1.1 Listing of deaths – Full Analysis Set
Country/
Center/
Patient/
Arm
Age/
Sex/
Race
Date of 
last dose
Study 
day of 
last 
dose
Date of death (phase)
Study day 
of death
Number days 
since last 
dose
Principal cause of 
death reported/ 
Preferred term
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY  xx
DDMMMYYYY 
(IND/CONS1/CONS2/TFR/ 
RE-TRT)
xx
xx 
XXXXXXXXXX/XXXXXXX
XXX/0XXX/0XXXX/X@
XX/X/XX
DDMMMYYYY  xx
DDMMMYYYY 
(IND/CONS1/CONS2/TFR/ 
RE-TRT)
xx #
xx *
XXXXXXXXXX/XXXXXXX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized. - Phase: IND = ind. phase (0-12 m), CONS1 = pre-rand. Cons. Phase
(12-24 m), CONS2 = post-rand. Cons phase (ARM 2)(24–36 m), TFR=Treat. free remission phase and
RE-TRT=re-treat. phase. The phase displayed indicates in which end of phase page the death has been recorded as the
primary reason to discontinue the study. If missing then death has been recorded in survival follow-up CRF pages.                
- Study day relative to the first day of treatment (day 1).
* Event occurred more than 30 days after last study treatment exposure date.
# Death occurring outside the treatment emergent period.
@ For patient #
 death occurred during Survival follow-up.
- Number of days since last dose = day of death – day of last dose + 1.
Listing 14.3.2-1.2 Listing of deaths SDV sensitivity – Full Analysis Set
<< Programming note: Same shell as Listing 14.3.2-1.1, for SDV sensitivity analysis>>
Add footnote:
- SDV sensitivity:  Excluding patient visits involved in SDV issues during final data review due to COVID-19


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Protocol No CAMN107AIC0
Listing 14.3.2-2.1   Listing of adverse events of special interest – Full Analysis Set
Country/
Center/
Patient/
Arm
Age/
Sex/
Race
Adverse Event Verbatim/
Abbreviated System organ class/
Preferred term
Start date
/day
End date
/day
Dur
(days)
Phase
Grade/Relation/
Action taken
/1
Verbatim/Ab SOCxxxxxx / 
PTxxxxxxxxxxx
16JUL2005/-2^
27JUL2005/13
12
IC
G1/NS/A0
Verbatim/Ab SOCxxxxxx / 
PTxxxxxxxxxxx
18JUL2005/4
27JUL2005/13
10
TFR
G1/S/A3,5
/2
Verbatim/Ab SOCxxxxxx / 
PTxxxxxxxxxxx
16JUL2005/-1*
27JUL2005/13
12
RE-TRT
G1/NS/A0
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- Phase: IC=Induction/Consolidation phase, TFR=TFR phase and RE-TRT=Re-treatment phase
- Relationship to study drug: NS=Not suspected, S=Suspected.
- Action taken: A0=No action taken, A1=Study drug dosage adjusted/temporarily interrupted, A2=Study drug 
permanently discontinued due to this AE, A3=Concomitant medication taken, A4=Non-drug therapy given, 
A5=Hospitalization/Prolonged hospitalization.
- Day is relative to the first day of treatment (day 1).
* Event occurred more than 30 days after the last study treatment exposure date. ^ Event occurred between
patient’s informed consent date and the day before first dose of study medication.
Listing 14.3.2-2.2  Listing of adverse events leading to study drug discontinuation – Full Analysis Set
<< Programming note: Same shell as listing 14.3.2-2.1 on adverse events leading to study drug discontinuation >>
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized. Phase: IC=Induction/Consolidation phase, TFR=TFR phase
and RE-TRT=Re-treatment phase.  Relationship to study drug: NS=Not suspected, S=Suspected.
- Action taken: A0=No action taken, A1=Study drug dosage adjusted/temporarily interrupted, A2=Study drug 
permanently discontinued due to this AE, A3=Concomitant medication taken, A4=Non-drug therapy given, 
A5=Hospitalization/Prolonged hospitalization. Day is relative to the first day of treatment (day 1).
* Event occurred more than 30 days after the last study treatment exposure date. ^ Event occurred between
patient’s informed consent date and the day before first dose of study medication.
- Patient #
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported 
as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
Add following footnote at the end of last page: 
- For patient #
 due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.


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Protocol No CAMN107AIC0
Listing 14.3.2-2.3   Listing of adverse events leading to study drug discontinuation during re-treatment phase 
– Subset of Full Analysis Set entering the re-treatment period
<< Programming note: Same shell as listing 14.3.2-2.1 on adverse events leading to study drug discontinuation during re-
treatment phase>>


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Protocol No CAMN107AIC0
Section 14.3.3 – Narratives of deaths, other serious and significant adverse events (non statistics and programming
deliverables)
This section does not require statistics and programming deliverables.
Section 14.3.4 – Abnormal laboratory value listings
Listing 14.3.4-1.1  Listing of abnormal hematology laboratory value – Full Analysis Set
Country/ Center/ 
Patient/ ARM
Age/ Sex/ 
Race
Phase/ Sample date/ 
Day
Test
Value
(SI unit)
Normal 
range
Grade
XXX/0XXX/0XXXX/X
XX/X/XX
ICONS1/CONS2/TFR/RE-
TRT/  DDMMMYYYY/ XX
XXXX
XX (LB/%)
L/N/H
Gx
ICONS1/CONS2/TFR/RE-
TRT/  DDMMMYYYY/ XX
XXXX
XX (LB/%)
L/N/H
Gx
XXX/0XXX/0XXXX/X
XX/X/XX
ICONS1/CONS2/TFR/RE-
TRT/  DDMMMYYYY/ XX
XXXX
XX (LB/%)
L/N/H
Gx
ICONS1/CONS2/TFR/RE-
TRT/  DDMMMYYYY/ XX
XXXX
XX (LB/%)
L/N/H
Gx
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native;
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Phase: IND = induction phase (0-12 months), CONS1 = pre-randomization consolidation phase (12-24 months),
CONS2 = post-randomization consolidation phase (ARM 2)(24–36 months), TFR=treatment free remission phase
and RE-TRT=re-treatment phase.
- L/H denotes a value below/above normal range, N denotes normal.
- Gx denotes an abnormal high value meeting toxicity CTCAE grading criteria and G-x an abnormal low value
according to toxicity CTCAE grading. Day is relative to the first day of treatment (day 1).
Listing 14.3.4-2.1  Listing of abnormal biochemistry laboratory value – Full Analysis Set
<< Programming note: Same shell as listing 14.3.4-1.1 >>


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Protocol No CAMN107AIC0
Section 16 – Appendices
Section 16.1 – Study information
Section 16.1.6 – Listing of patients receiving test drug(s)/investigational product(s) from specific batches where more 
than one batch was used
Not applicable
Listings (Section 16.1.6)


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Section 16.1.7 – Randomization scheme and codes (subject identification and treatment assigned)
Listing 16.1.7-1.1 Randomization schemes - Randomized patients
Subject ID
Country/ 
Center/
Patient
Age/
Sex/
Race
Randomization 
date/ Study day 
Randomized 
Treatment
Received  
Treatment
DDMMMYYYY/ xx
Arm 1
Arm 1
- Randomized patients are all patients meeting eligibility criteria for randomization
(i.e. achieved a sustained MR4.0 for at least 12 months in the induction/consolidation phase of the study).
- Arm 1: Pre-randomization treatment 24 months, TFR up to 36 months, Re-treatment up to 36 months
- Arm 2: Pre-randomization treatment 24 months, Post-randomization treatment 12 months, TFR up to 24 months,
Re-treatment up to 24 months.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native;
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.


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Listings (Section 16.1.7)
Section 16.1.9 – Documentation of statistical methods
This section should include figures, tables and listings for the following data (where applicable):

inferential analysis outputs for primary & key secondary variables (e.g. additional SAS output)

any additional information needed about non-inferential analysis outputs 
Refer to Guidelines for content of Statistical Appendices of the Clinical Study Report (G029_01)
Guidelines for content of Statistical Appendices of the Clinical Study Report, is available in Cabinets/CREDI TABULU/B&SR/CIS Process 
Documentation/Guidances (outside of ESOPS)
Attach here shells (a pictorial representation of what the table will look like) or specification (a structured description of a table in words) 
for each Section 16.1.9 table. Where the layout of a table is exactly the same as a previous table, perhaps with only the population indicator 
changing, there is no need to repeat the shell each time, simply refer to the previous layout.   
Shells may be formatted text or SAS output.  Repetition of Section 14 tables is not appropriate.


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Listing 16.1.9.1 Raw Statistical output from Demographic and characteristics at baseline– Full Analysis Set
                                                                                    Insert the contents of the SAS Output Window here.
<<Programming note: 
Based on Table 14.1-3.1 Demographic and characteristics at baseline– Full Analysis Set >>
Listing 16.1.9.1.1 Raw Statistical output from Demographic and characteristics at baseline– LSC sub-study Full 
Analysis Set
<<Programming note: 
Based on Table 14.1-3.1.1 Demographic and characteristics at baseline– LSC sub-study FAS >>
Listing 16.1.9.2 Raw Statistical output from History of prior Imatinib therapy – Full Analysis Set
<<Programming note: 
Based on Table 14.1-5.1 Demographic and characteristics at baseline– Full Analysis Set >>
Listing 16.1.9.2.1 Raw Statistical output from History of prior Imatinib therapy – LSC sub-study Full Analysis 
Set
<<Programming note: 
Based on Table 14.1-5.1.1 Demographic and characteristics at baseline–LSC sub-study FAS >>


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Listing 16.1.9.3    Raw Statistical output from Cardiovascular risk factors at baseline – Full Analysis Set
<<Programming note: 
Based on Table 14.1-6.1 Demographic and characteristics at baseline– Full Analysis Set >>
Listing 16.1.9.4.1   Raw Statistical output from Molecular response MR4.0 at 12 months of TFR–Subset of Full 
Analysis Set entering the TFR phase
<<Programming note: 
Based on Table 14.2-2.1.1 
Listing 16.1.9.4.2   Raw Statistical output from Molecular response MR4.0 at 12 months of TFR–Subset of Per 
Protocol Analysis Set entering the TFR phase
<<Programming note: 
Based on Table 14.2-2.1.2 Molecular response MR4.0 at 12 months of TFR–Subset of Per Protocol Set entering the TFR phase >>


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Listing 16.1.9.5.1   Raw Statistical output from Kaplan-Meier analysis of treatment-free survival during the TFR 
phase – Subset of Full Analysis Set entering the TFR phase
<<Programming note: 
Based on Table 14.2-2.2.1  Kaplan-Meier analysis of treatment-free survival during the TFR phase – Subset of Full Analysis 
Set entering the TFR phase >>
Listing 16.1.9.5.2   Raw Statistical output from Kaplan-Meier analysis of treatment-free survival during the TFR 
phase – Subset of Per Protocol Analysis Set entering the TFR phase
<<Programming note: 
Based on Table 14.2-2.2.2  Kaplan-Meier analysis of treatment-free survival during the TFR phase – Subset of Per Protocol 
Analysis Set entering the TFR phase >>
Listing 16.1.9.5.3   Raw Statistical output from Kaplan-Meier analysis of overall survival from Randomization–
Randomized Set
<<Programming note: 
Based on Table 14.2-2.3  Kaplan-Meier analysis of overall survival from Randomization–Randomized Set >>
Listing 16.1.9.5.4   Raw Statistical output from Kaplan-Meier analysis of progression-free survival during the 
TFR phase – Subset of Full Analysis Set entering the TFR phase
<<Programming note: 
Based on Table 14.2-2.4  Kaplan-Meier analysis of progression-free survival during the TFR phase – Subset of Full Analysis 
Set entering the TFR phase >>


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Listing 16.1.9.6.1   Raw Statistical output from Kaplan-Meier estimate of time-to-first CVEs during the pre-
randomization induction/consolidation phase – Full analysis set
<<Programming note: 
Based on Table 14.3.1-11.1.1  Kaplan-Meier analysis of time-to-first CVEs during the pre-randomization 
induction/consolidation phase – Full analysis set >>
Listing 16.1.9.6.2   Raw Statistical output from Kaplan-Meier estimate of time-to-first CVEs during the post-
randomization consolidation phase (ARM 2)– Subset of Full Analysis Set patients randomized on Arm 
2
<<Programming note: 
Based on Table 14.3.1-11.1.2  Kaplan-Meier estimate of time-to-first CVEs during the post-randomization consolidation phase 
(ARM 2)– Subset of Full Analysis Set patients randomized on Arm 2>>
Listing 16.1.9.6.3   Raw Statistical output from Kaplan-Meier estimate of time-to-first CVEs during the re-
treatment phase – Subset of Full Analysis Set entering the re-treatment phase
<<Programming note: 
Based on Table 14.3.1-11.2  Kaplan-Meier estimate of time-to-first CVEs during the re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase >>


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Tables (Section 16.1.9)


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Section 16.2 – Patient data listings
Listing 16.2-1.1 Enrolled patients 
Country/ Center/ 
Patient / ARM
Age/ 
Sex/ 
Race
Date of 
enrollment
Date of 
first
dose of 
Nilotinib
Date of last 
dose of 
Nilotinib 
(phase)
Patient 
entered 
the re-
treatment 
phase
Date of 
last 
contact
Study 
completion
Study phase
discontinuation
Principal cause 
of phase
discontinuation
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY
DDMMMYYYY
DDMMMYYYY/IND
Yes/No
DDMMMYYYY
Yes/No
Yes/No
XXXXX
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY
DDMMMYYYY
DDMMMYYYY/IND
Yes/No
DDMMMYYYY
Yes/No
Yes/No
XXXXX
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY
DDMMMYYYY
DDMMMYYYY/RE-
TRT
Yes/No
DDMMMYYYY
Yes/No
Yes/No
XXXXX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Phase: IND = induction phase (0-12 months), CONS1 = pre-randomization consolidation phase (12-24 months), CONS2 = post-
randomization consolidation phase (ARM 2)(24–36 months), TFR=treatment free remission phase and RE-TRT=re-treatment phase.
- Study completion is when EOS visit indicates that study period of 5 years is completed by patient.
<< Programming note: For different causes of phase discontinuation use “-“ as separator.


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Section 16.2.1 – Discontinued subjects
Listing 16.2.1-1.1 Treatment and study completion - Safety Set
Country/          Age/     Last known    Day       End of study     
Center/           Sex/      date on    of last     Primary          Followed        Death      
Patient/ Arm      Race       study       dose      reason #         for survival*   Date/Day   
                            treatment   
_
____
_______________________________________________________________________________________________ 
X 
 07NOV2005     116         1               Yes         27NOV2005/136                         
X 
 15SEP2005      14         2               Yes                                   
X 
 02MAY2006     134         7               No                                            
X 
 16MAR2006      17         7               No             
   
                 
X 
 23OCT2006     119         1               No              
X 
 01DEC2006      15        10               No                                                
  
                                                                        
- Arm: - Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized. The last known date on study treatment will be taken 
from DAR page. Day of last dose and Day of death are relative to the first day of treatment (day 1).                                   
# Reason: 1=Adverse event(s), 2=Abnormal laboratory value(s), 3=Abnormal test procedure result(s),                  
7=Subject withdrew consent, 8=Lost to follow-up, 9=Administrative problems,  10=Death, 16=New cancer (CML) 
therapy, 17=Disease progression (CML),  25=Protocol deviation, 88=Other, 89=Unstable MR4.0, 90=Pregnancy.
* Does the subject continue to be followed for survival, stem cell transplantation and disease prog. to AP/BC?
- Patient #
reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported 
as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.


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Listing 16.2.1-1.2 Study discontinuation – Full Analysis Set
Phase
Country/ Center/ 
Patient / ARM
Age/ Sex/ 
Race
Date of last 
dose
Date of end of  
phase
Reason for 
discontinuation
Followed for 
survival
CONS1
XXX/0XXX/0XXXX/2
XX/X/XX
DDMMMYYYY
DDMMMYYYY
XXXXX
Yes/No
XXX/0XXX/0XXXX/2
XX/X/XX
DDMMMYYYY
DDMMMYYYY
XXXXX
Yes/No
CONS2
XXX/0XXX/0XXXX/2
XX/X/XX
DDMMMYYYY
DDMMMYYYY
XXXXX
Yes/No
XXX/0XXX/0XXXX/2
XX/X/XX
DDMMMYYYY
DDMMMYYYY
XXXXX
Yes/No
TFR
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY
DDMMMYYYY
XXXXX
Yes/No
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY
DDMMMYYYY
XXXXX
Yes/No
RE-TRT
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY
DDMMMYYYY
XXXXX
Yes/No
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY
DDMMMYYYY
XXXXX
Yes/No
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native;
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Phase: IND = induction phase (0-12 months), CONS1 = pre-randomization consolidation phase (12-24 months),
CONS2 = post-randomization consolidation phase (ARM 2)(24–36 months), TFR=treatment free remission phase and RE-TRT=re-
treatment phase.
@ For patient #
 death occurred during Survival follow-up.
- Patient 
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported 
as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.


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Listing 16.2.1-1.3 Screen failures (All subjects enrolled)
Country/
Center/
Patient 
Age/
Sex/
Race
Date of 
Screening
Criteria not met
Number
Protocol 
Version
Specific text
0XXXX
DDMMMYYYY
IC1
V1
Male or female patients, aged ≥18 years
0XXXX 
DDMMMYYYY
IC3
V0
Documented confirmed diagnosis of chronic phase Ph+ 
and/or BCR-ABL+ CML-CP.
0XXXX 
DDMMMYYYY
IC1 / IC7
V2
Male or female patients, aged ≥18 years / 
Patients must have the following electrolyte values 
within normal limits at screening
analysis, or corrected to within normal limits with 
supplements prior to the first dose of
study medication
XXXX 
DDMMMYYYY
IC5 / EC3
V4
Patient in CCyR (A patient with MMR is considered to be 
in CCyR 
/ 
Severe and/or uncontrolled concurrent medical disease
..
-
M: Male; F: Female; 
-
W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native;
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.


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Section 16.2.2 – Protocol deviations
Listing 16.2.2-1.1 Protocol deviations – Enrolled patients 
Country/ Center/ 
Patient/ Arm
Age/ Sex/ Race
Deviation Category
Description of 
Deviation
XXX/0XXX/0XXXX/X
XX/X/XX
Eligibility/Inclusion
XXXXX
XXX/0XXX/0XXXX/X
XX/X/XX
Eligibility/Inclusion
XXXXX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Only major protocol deviation were reported in this listing.


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Section 16.2.3 – Patients excluded from the efficacy analysis
Listing 16.2.3-1.1 Analysis set – All patients 
Country/ Center/ 
Patient/ Arm
Age/ Sex/ 
Race
Enrolled 
patients
Full 
Analysis 
Set
Randomized 
Set 
Per 
Protocol
Set
Safety 
Set
XXX/0XXX/0XXXX/X
XX/X/XX
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
XXX/0XXX/0XXXX/X
XX/X/XX
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Full Analysis Set (FAS) comprises all subjects who are enrolled, excluding patients with PD severity codes: 0, 8.
- Per Protocol Analysis Set (PPS) comprises all subjects who are enrolled without major protocol deviation (PD severity 
codes: 0, 1, 5, 8).
- Safety Set consists of all patients who received at least one dose of study drug, excluding patients with PD severity 
codes: 0, 5, 8.   


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Section 16.2.4 – Demographics and data at screening
Listing 16.2.4-1.1 Demographic data – Full Analysis Set
Country/ Center/ 
Patient/ Arm
Age 
(years)
Sex
If female, 
child bearing 
potential*
Race (if 
other, 
specify)**
ECOG
BMI
Smoking 
status
If ex-
smoker, 
duration 
(months)
If smoker 
or ex-smoker, 
use of tobacco p
roduct in the
past month***
XXX/0XXX/0XXXX/X
XX
F/M
XXXXX
XXXXX
0-5
XX
No/Yes/Ex
XX
XXXXX
XXX/0XXX/0XXXX/X
XX
F/M
XXXXX
XXXXX
0-5
XX
No/Yes/Ex
XX
XXXXX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
* Able to bear children/ Premenarche/ Post menopausal/ Sterile - of child bearing age.
** Caucasian/ Black/ Asian/ Native american/ North african descent/ Unknown/ Other.
*** Cigarettes (including roll-ups/ Cigars/ Tobacco (e.g. pipe)/ Others (e.g. nicotine patches, chewing tobacco).
Listing 16.2.4-2.1 Family history – Full Analysis Set
Country/ Center/ 
Patient/ Arm
Age/ Sex/ 
Race
Diabetes
Hypertension
Dyslipidemia
Cardiac 
events
Cerebrovascular 
events
Peripheral 
arterial 
disease
XXX/0XXX/0XXXX/X
XX/X/XX
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
XXX/0XXX/0XXXX/X
XX/X/XX
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.


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Listing 16.2.4-2.2 Disease history– Full Analysis Set
Time from 
initial 
diagnosis 
to 
screening 
(months)
Peripheral 
blood blast 
at 
diagnosis  
(%)
PB 
basophils 
at 
diagnosis 
(%)
Platelets 
at 
diagnosis  
(109L)
Spleen 
size 
(cm)
Extrame-
dullary 
invol-
vement
Sokal/
Euro 
(Hasfo
rd)/ 
EUTOS
Score 
(risk)
Molecular 
response at 
screening
(BCR-ABL(IS))
Previous 
progression 
to AP-BP / 
Attempt to 
stop 
treatment 
with 
Imatinib / 
Have known 
atypical 
transcript 
Country: xxx, Center: xxx, Patient: xxx, arm: 1/2
Age: xxx, Sex: xxx, Race: xxx
xx
XX
XX
XX
XX
XX
High/
Low/Lo
w
>0.01% - <=0.1%
Yes/No/Yes
Country: xxx, Center: xxx, Patient: xxx, arm: 1/2
Age: xxx, Sex: xxx, Race: xxx
xx
XX
XX
XX
XX
XX
Low/In
termme
diate/
High
Undetetable
Yes/No/No
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Time since initial diagnosis = (date of the baseline visit - date of initial diagnosis)/30.4375.
- Extramedullary involvement other than hepato and/or splenomegaly.
- Sokal score: low risk (<0.8), intermediate risk (>=0.8-<=1.2) and high risk (>1.2).
- Euro (Hasford) score: low risk (<=780), intermediate risk (>780-<=1480) and high risk (>1480).
- EUTOS score: low risk (<=87) and high risk (>87).
- Molecular response: BCR-ABL (IS): Undetectable; <=0.01%; >0.01% - <=0.1%; >0.1% - <=1%; >1%.  


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Listing 16.2.4-3.1 Disease history I– Full Analysis Set
Diagnosis
Country/ 
Center/ 
Patient/ 
Arm
Age/ 
Sex/ 
Race
Time 
since
initial 
diagnosis 
(months)
Peripheral 
blood 
blasts % 
PB 
eosinophilis/
Basophilis %
Platelets at
diagnosis (10E9/L)
Spleen 
size 
(cm)
Extramedullary involvement 
other than hepato and/or 
splenomegaly 
XXX/0XXX/0
XXXX/X
XX/X/XX
xx.x
xx.x
xx.x
xx.x
xx.x
No
XXX/0XXX/0
XXXX/X
XX/X/XX
xx.x
xx.x
xx.x
xx.x
xx.x
Yes
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.


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Listing 16.2.4-3.2  Disease history II– Full Analysis Set
Country/ 
Center/ 
Patient/ 
Arm
Age/ 
Sex/ 
Race
Time since
initial 
diagnosis 
(months)
Sokal/
Euro
(Hasford) / 
EUTOS 
score
Sokal 
score 
category
Previous 
progressio
n to AP/BC
Attempt to stop
treatment
with Imatinib
Molecular response 
at Baseline (BCR-
ABL(IS))
XXX/0XXX/0
XXXX/X
XX/X/X
X
xx.x
xx.x / xx.x / xx.x
low risk
Yes
Yes
>1%
XXX/0XXX/0
XXXX/X
XX/X/X
X
xx.x
xx.x / xx.x / xx.x
intermedia
te risk
No
No
Undetectable
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native;
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Sokal score: low risk (<0.8), intermediate risk (>=0.8-<=1.2) and high risk (>1.2).
- Baseline is defined as the last available assessment before or at date of start of study treatment.
- Molecular response: BCR-ABL (IS): Undetectable; <=0.01%; >0.01% - <=0.1%; >0.1% - <=1%; >1%.  
Listing 16.2.4-3.3  Medical history/current medical condition – Full Analysis Set
Country/ Center/ 
Patient/ Arm
Age/ Sex/ 
Race
MedDRA SOC/ Preferred 
term/ Verbatim
Date of 
diagnosis/Surgery
Ongoing
XXX/0XXX/0XXXX/X
XX/X/XX
SOCXXXXX/PTXXXXX/XXXXX
DDMMMYYYY
Yes/No
XXX/0XXX/0XXXX/X
XX/X/XX
SOCXXXXX/PTXXXXX/XXXXX
DDMMMYYYY
Yes/No
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.


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Listing 16.2.4.4  
Cardiovascular risk factors at baseline for patients with not evaluable CV risk factor, Full 
Analysis Set
CVEs 
history
Diabetes 
mellitus  
history
Hypertension 
history
Severe 
hypertension 
history
Dyslipidemia 
history
Familial 
dyslipidemia 
history
Systolic 
blood 
pressure 
(mmHg)
Total 
cholesterol
(mmol/L)
Micro-
albuminuria
(mg/L)
Creatinine 
(umol/L)
G
F
R
Heart
score
Country: xxx, Center: xxx, Patient: xxx, Age: xxx, Sex: xxx, Race: xxx
Smoking status: xxx, Weight (kg): xxx, BMI (kg/m2): xx.x
Date of first study medication: DDMMMYYYY
Yes (IHD/ 
PAOD/ ICE/ 
OTHER) /No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
xx
xx
xx
xx
x
x
xx
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- IHD: Ischemic heart disease, PAOD: Peripheral arterial occlusive disease, ICE: Ischemic cerebrovascular events.
- GFR measured by Cockcroft-Gault Creatinine Clearance rate as defined below: 
GFR = [(140-age)*weight (kg)*0.85 (for women)] / [Cr (umol/l)*0.814].
- HeartScore defined by the European Guidelines on cardiovascular disease prevention in clinical practice 
(version 2012) and based on age, gender, smoking status, systolic blood pressure, total cholesterol and country.
<<Programming note:
Date of first study medication: STTEXP1O [derived.a_ dar]
CVEs history: CVEMH [derived.a_ ident]
Diabetes mellitus history: CVDBTMH [derived.a_ ident]
Hypertension history: CVHYPMH [derived.a_ ident]
Severe hypertension history: CVSEHYMH [derived.a_ ident]
Dyslipidemia history: CVDYSMH [derived.a_ ident]
Familial dyslipidemia history: CVFADYMH [derived.a_ ident]
Systolic Blood pressure: STNSBPB [derived.a_ ident]
Total cholesterol: TCHOLB [derived.a_ ident]
Micro-albuminuria : UMALBB [derived.a_ ident]
Creatinine: CREATB [derived.a_ ident]
GFR: CVGFR [derived.a_ident]
Heart Score: HSCORE [derived.a_ident] >>


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Section 16.2.5 – Compliance and/or drug concentration data if available (including Bioanalytical Data Report)
Listing 16.2.5-1.1 Dosage administration records – Full Analysis Set
Country/ Center/ 
Patient/ Arm
Age/ Sex/ 
Race
Drug administration
Start/End dates
Phase
Total Dose 
(mg/day)/ Frequency
Discontinuation*
Reason for 
Discontinuation
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY/ DDMMMYYYY
IND/CONS
XX/XX
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY/ DDMMMYYYY
TFR 
XX/XX
XXX/0XXX/0XXXX/X
XX/X/XX
DDMMMYYYY/ DDMMMYYYY
RE-TRT
XX/XX
XXXXX
XXXXX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
* Discontinuation: None/Changed/Interrupted/Permanently.
- Phase: IND/CONS = induction/consolidation phase, TFR=treatment free remission phase and RE-TRT=re-treatment phase.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Patient #
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported 
as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
Section 16.2.6 – Individual efficacy response data
Listing 16.2.6-1.1 BCR-ABL(IS) ratio and molecular responses during Induction/Consolidation and post-
randomization consolidation phase (ARM 2) – Full Analysis Set
Country/ Center/ 
Patient/ Arm
Age/ Sex/ Race
Visit
Time-
window/Day
BCR-ABL(IS) 
ratio (%)
Total number of 
ABL copies
Molecular response
XXX/0XXX/0XXXX/X
XX/X/XX
Baseline
XX
XX
MMR/MR4.0/MR4.5
3M
XX
XX
MMR/MR4.0/MR4.5
Repeat at each time-point every 3 month till 24/36 months
XXX/0XXX/0XXXX/X
XX/X/XX
Baseline
XX
XX
MMR/MR4.0/MR4.5
3M
XX
XX
MMR/MR4.0/MR4.5
Repeat at each time-point every 3 month till 24/36 months
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.


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- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
- Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
Listing 16.2.6-1.2 BCR-ABL(IS) ratio and molecular responses during TFR phase – Subset of Full Analysis Set
entering the TFR phase
Country/ Center/ 
Patient/ Arm
Age/ Sex/ Race
Visit
Time-
window/Day
BCR-ABL(IS) 
ratio (%)
Total number of 
ABL copies
Molecular response
XXX/0XXX/0XXXX/X
XX/X/XX
Baseline
XX
XX
MMR/MR4.0/MR4.5
3M
XX
XX
MMR/MR4.0/MR4.5
Repeat at each time-point every 3 month till 24/36 months
XXX/0XXX/0XXXX/X
XX/X/XX
Baseline
XX
XX
MMR/MR4.0/MR4.5
3M
XX
XX
MMR/MR4.0/MR4.5
Repeat at each time-point every 3 month till 24/36 months
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native;
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Patients randomized to Arm 1 have a miximun of 36 months of TFR phase; 
- Patients randomized to Arm 2 have a maximun of 24 months of TFR phase;
Listing 16.2.6-1.3 BCR-ABL(IS) ratio and molecular responses during re-treatment phase – Subset of Full 
Analysis Set entering the re-treatment phase
<< Same shell as listing 16.2.6-1.2 with the following second footnote:
- Patients randomized to Arm 1 have 24 months of treatment and a maximum of 36 months of re-treatment.
- Patients randomized to Arm 2 have 36 months of treatment and a maximum of 24 months of re-treatment.
>>


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Listing 16.2.6-2.1 Criteria of successful TFR – Subset of Full Analysis Set entering the TFR phase
Country/ Center/ 
Patient/ Arm
Age/ 
Sex/ 
Race
Visit
Time-window/ 
Day
Loss of 
MMR
Loss of 
MR4.0
Confirmed 
loss of 
MR4.0
Re-start of 
Nilotinib
Successful 
TFR at 
Month 12
XXX/0XXX/0XXXX/X
XX/X/XX
V101-A1-Month 1
M1/35
Yes/No
Yes/No
Yes/No
Yes/No
V106-A1-Month 6
M6/190
Yes/No
Yes/No
Yes/No
Yes/No
Repeat at all TFR visits
V109-A1-Month 12
M12/408
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
V401-EOP-TFR
M12/420
Yes/No
Yes/No
Yes/No
Yes/No
XXX/0XXX/0XXXX/X
XX/X/XX
M3/90
Yes/No
Yes/No
Yes/No
Yes/No
M6/190
Yes/No
Yes/No
Yes/No
Yes/No
Repeat at all TFR visits
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
* in case of unsuccessful TFR, put ‘No’ on the row with confirmed loss of MR4.0=Yes or re-start of nilotinib=Yes.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Confirmed loss of MR4.0 defined as three consecutive tests less than MR4.0 assessed at three consecutive visits.
- Successful TFR is defined as MR4.0, no confirmed loss of MR4.0, no loss of MMR and no re-starting 
of nilotinib therapy at the end of 12 months in the TFR phase of the study.
- Patients randomized to Arm 1 have a maximun of 36 months of TFR phase; Patients randomized to Arm 2
have a maximum of 24 months of TFR phase;


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Listing 16.2.6-3.1 Assessment of progression-free survival during the TFR phase –Subset of Full Analysis Set
entering the TFR phase
Country/ Center/ 
Patient/Arm
Age/ Sex/ 
Race
Progression
Date of 
progression
Time to 
progression/censoring
(months)
Type of 
progression
XXX/0XXX/0XXXX\X
XX/X/XX
Yes/No
DDMMMYYYY
XX
XXXXX
XXX/0XXX/0XXXX\X
XX/X/XX
Yes/No
DDMMMYYYY
XX
XXXXX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native;
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Event = first occurrence of progression to AP/BC or death for any cause.
Censoring rule = patients who did not meet the event are censored at the first date occurring between: the last 
contact date, the end of TFR phase, the DBL date and the date of death. 
- Time to event = (date of event – start date of TFR phase + 1)/30.4375. 
- Patients randomized to Arm 1 have a miximun of 36 months of TFR phase; Patients randomized to Arm 2 have a
maximum of 24 months of TFR phase.


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Listing 16.2.6-3.2 Assessment of treatment-free survival during the TFR phase –Subset of Full Analysis Set 
entering the TFR phase
Country/ Center/ 
Patient/Arm
Age/ Sex/ 
Race
Treatment 
free
Date of event
Time from Day 1 of 
TFR to 
event/censoring
(months)
Type of event
XXX/0XXX/0XXXX\X
XX/X/XX
Yes/No
DDMMMYYYY
XX
XXXXX
XXX/0XXX/0XXXX\X
XX/X/XX
Yes/No
DDMMMYYYY
XX
XXXXX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Event = first occurrence of relapse, re-treatment with nilotinib, progression to AP/BC or death for any cause.
Censoring rule = patients who did not meet the event are censored at the first date occurring between: the last
contact date, the end of TFR phase, the DBL date and the date of death. 
- Time to event = (date of event – start date of TFR phase + 1)/30.4375. 
- Patients randomized to Arm 1 have a miximun of 36 months of TFR phase; Patients randomized to Arm 2 have a 
maximum of 24 months of TFR phase.


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Listing 16.2.6-3.3 Assessment of overall survival From Randomization – Randomized set 
Country/ Center/ 
Patient/Arm
Age/ Sex/ 
Race
Alive
Date of event(death)
Time from 
Randomization to 
death /censoring 
(months)
XXX/0XXX/0XXXX\X
XX/X/XX
Yes/No
DDMMMYYYY
XX
XXX/0XXX/0XXXX\X
XX/X/XX
Yes/No
DDMMMYYYY
XX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Event = death for any cause.
Censoring rule = patients who did not meet the event are censored at the first date occurring between: the last
contact date, and the date of death. 
- Time to event = (date of event – Randomization date + 1)/30.4375.


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Listing 16.2.6-3.4 Assessment of relapse and treatment status during the TFR phase –Subset of Full Analysis 
Set entering the TFR phase and relapsed
Start of re-treatment after Relapse
Country/ Center/ 
Patient/Arm
Age/ 
Sex/ 
Race
Date of 
Relapse
Time from 
Day 1 of TFR
to relapse
(months)
Re-treatment
Date
Days after relapse.
XXX/0XXX/0XXXX\X
XX/X/XX
DDMMMYYYY
XX
Yes
DDMMMYYYY
XX
XXX/0XXX/0XXXX\X
XX/X/XX
DDMMMYYYY
XX
No
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Time to event = (date of relapse – start date of TFR phase + 1)/30.4375. 
- Patients randomized to Arm 1 have a maximum of 36 months of TFR phase; Patients randomized to Arm 2 have a 
maximum of 24 months of TFR phase;


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Listing 16.2.6-4.1    WBC and molecular response in patients with WBC increase (CTCAE grade>G1) – Full 
Analysis Set
Country/        Age/                           
Molecular
Center/         Sex/      Time-               Lab sample          WBC            RQ-PCR sample        Response             
Patient/Arm     Race/     point     Visit     date/day           10E9/L         date/day           eCRF  Derived              
____________________________________________________________________________________________________________________________
/X
  M3        V1-M3    xxxxxxxx/98       xxx Gx         xxxxxxxxx/98        MMR
MMR                
  
  M6        V2-M6                                      xxxxxxxxx/183       MR4.0
MR4.0             
  
  M6        UNSCH     xxxxxxxx/186      xxx Gx                                             
  
                                                                                                 
/X
  xx        xxxxx     xxxxxxxx/xxx      xxx Gx         xxxxxxxx/xxx        xxxx
xxxx                
  
  xx        xxxxx     xxxxxxxx/xxx      xxx Gx         xxxxxxxx/xxx        xxxx
xxxx               
  
  xx        xxxxx     xxxxxxxx/xxx      xxx Gx         xxxxxxxx/xxx        xxxx
xxxx                 
                           xx        xxxxx     xxxxxxxx/xxx      xxx Gx         xxxxxxxx/xxx        xxxx
xxxx                    
                                                                                                                                
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- Gx denotes a value meeting toxicity grading criteria (NCI-CTCAE version 4.03).
- Note: EOP = End Of Phase; UNSCH = Unscheduled visit.
<<Programming note: For each patient merge PCR data with haematological data by time-point and visit. If there are several unscheduled visit 
in a time-window then merge them by incremental order defined by chronology >>;


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Protocol No CAMN107AIC0
Listing 16.2.6-5.1  Individual Efficacy data, Molecular response – Full Analysis Set
Molecular 
Response
Country/
Center/
Patient/Arm
Age/
Sex/
Race
Time-
point
Visit
Evaluation 
was not 
done
RQ-PCR 
sample
date/day
Evaluation 
not
evaluable
Total 
ABL 
copies 
BCR-
ABL 
(IS) 
(%)
eCRF
Derived
/x
M3       V1-M3
xxxxxxxxx/98
xxxxxx
xx.x
3
3
M6       V2-M6
N.D.
… 
… 
…
… 
…
… 
… 
… 
… 
… 
… 
…
… 
N.E.
/x
MX       VX-MX
xxxxxxxxx/XX
xxxxxx
xx.x
3
3
MX     
VX-MX
xxxxxxxxx/XX
xxxxxx
xx.x
4.0
4.0
… 
… 
…
… 
…
… 
… 
… 
… 
… 
… 
…
… 
…
… 
… 
… 
… 
/x
MX       VX-MX
xxxxxxxxx/XX
xxxxxx
xx.x
4.0
3.0
MX     
VX-MX
xxxxxxxxx/XX
xxxxxx
xx.x
5.0
4.5
… 
… 
… 
… 
… 
… 
… 
… 
… 
… 
…
… 
…
… 
… 
… 
… 
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- Note: EOP = End Of Phase; UNSCH = Unscheduled visit, N.D.: Not Done, N.E.: Not evaluable.


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Listing 16.2.6-5.2  Individual Efficacy data, Bone-marrow I – Full Analysis Set
Percent of
Country/
Center/
Patient/Arm
Age/
Sex/
Race
Time-
point
Visit
Evaluat
ion was 
not 
done
Bone-arrow 
sample
date/day
Bone marrow 
sample 
collected
Cellularity
Blasts
Pro
Myelo-
cytes
Baso-
philis
Eosino-
philis
M3      V1-M3
xxxxxxxxx/98
Aspirate
Hypocellular
xx.x
xx.x
xx.x
xx.x
M6      V2-M6
N.D.
… 
… 
…
… 
… 
… 
… 
… 
… 
… 
…
… 
… 
… 
… 
… 
MX      VX-MX
xxxxxxxxx/XX
Aspirate
Normocellular
xx.x
xx.x
xx.x
xx.x
MX     
VX-MX
xxxxxxxxx/XX
Aspirate
Hypocellular
xx.x
xx.x
xx.x
xx.x
… 
… 
…
… 
… 
… 
… 
… 
… 
… 
…
… 
… 
… 
… 
… 
MX      VX-MX
xxxxxxxxx/XX
Biopsy
Normocellular
xx.x
xx.x
xx.x
xx.x
MX     
VX-MX
xxxxxxxxx/XX
Aspirate
Hypocellular
xx.x
xx.x
xx.x
xx.x
… 
… 
… 
… 
… 
… 
… 
… 
…
… 
… 
… 
… 
… 
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- Note: EOP = End Of Phase; UNSCH = Unscheduled visit, N.D.: Not Done.


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Listing 16.2.6-5.3  Individual Efficacy data, Bone -marrow II – Full Analysis Set
Number of metaphases
Additional 
aberrations
Country/
Center/
Patient/Arm
Age/
Sex/
Race
Time-
point
Visit
Evaluat
ion was 
not 
done
Bone-arrow 
sample
date/day
Bone marrow 
sample 
collected
Analyzed
Ph +
Ph -
Ph +
Ph -
/x
M3      V1-M3
xxxxxxxxx/98
Aspirate
xxx
xxx
xxx
Yes
No
M6      V2-M6
xxxxxxxxx/186
Biopsy
xxx
xxx
xxx
No
No
… 
… 
…
… 
…
…
…
…
…
… 
… 
… 
… 
…
… 
…
…
…
…
…
\x
MX      VX-MX
xxxxxxxxx/XX
Aspirate
xxx
xxx
xxx
No
Yes
MX     
VX-MX
N.D.
… 
… 
…
… 
…
…
…
…
…
… 
… 
… 
… 
…
… 
…
…
…
…
…
/x
MX      VX-MX
xxxxxxxxx/XX
Biopsy
xxx
xxx
xxx
No
No
MX     
VX-MX
xxxxxxxxx/XX
Aspirate
xxx
xxx
xxx
Yes
Yes
… 
… 
… 
…
…
…
…
… 
… 
… 
… 
…
… 
…
…
…
…
…
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- Note: EOP = End Of Phase; UNSCH = Unscheduled visit, N.D.: Not Done.


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Protocol No CAMN107AIC0
Listing 16.2.6-6.1.1 Total percentage of CD34+ cells – LSC sub-study Full Analysis Set
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other. 
# Baseline value, latest available valid evaluation between Screening and Rescreening.                              
Country/ Center/ Patient/ Arm
Age/ Sex/ Race
Time point
Total CD34+
XXX/0XXX/0XXXX/X
XX/X/XX
Screening#
XXX.X
XXX/0XXX/0XXXX/X
XX/X/XX
Month 24
XXX.X
XXX/0XXX/0XXXX/X
XX/X/XX
Month 36
XXX.X
XXX/0XXX/0XXXX/X
XX/X/XX
EOP TFR
XXX.X


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Protocol No CAMN107AIC0
Listing 16.2.6-6.2.1 Percentage of cells from total CD34 positive– LSC sub-study Full Analysis Set
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; 
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other. 
# Baseline value, latest available valid evaluation between Screening and Rescreening.
Percentage from total CD34+
Country/ Center/ 
Patient/ Arm
Age/ 
Sex/ 
Race
Time
point
CD34+/CD38+
CD34+/CD38-
Immunopheno-
typically
Aberrant
CD34+ cells
Immunopheno-
typically
Aberrant CD34
Negative cells
XXX/0XXX/0XXXX/X
XX/X/XX
Screening#
XXX.X
XXX.X
XXX.X
XXX.X
Month 24
XXX.X
XXX.X
XXX.X
XXX.X
Month 36
XXX.X
XXX.X
XXX.X
XXX.X
EOP TFR
XXX.X
XXX.X
XXX.X
XXX.X
XXX/0XXX/0XXXX/X
XX/X/XX
Screening
XXX.X
XXX.X
XXX.X
XXX.X
Re-screening#
XXX.X
XXX.X
XXX.X
XXX.X
Month 24
XXX.X
XXX.X
XXX.X
XXX.X
Month 36
XXX.X
XXX.X
XXX.X
XXX.X
EOP TFR
XXX.X
XXX.X
XXX.X
XXX.X


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Protocol No CAMN107AIC0
Listing 16.2.6-6.3.1 Number of events sorted– LSC sub-study Full Analysis Set
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native;
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other. 
# Baseline value, latest available valid evaluation between Screening and Rescreening.
Country/ Center/ 
Patient/ Arm
Age/ 
Sex/ 
Race
Time
point
CD34+/CD38+
CD34+/CD38-
Immunopheno-
typically
Aberrant
CD34+ cells
Immunopheno-
typically 
Aberrant CD34 
negative cells
XXX/0XXX/0XXXX/X
XX/X/XX
Screening#
XXX.X
XXX.X
XXX.X
XXX.X
Month 24
XXX.X
XXX.X
XXX.X
XXX.X
Month 36
XXX.X
XXX.X
XXX.X
XXX.X
EOP TFR
XXX.X
XXX.X
XXX.X
XXX.X
XXX/0XXX/0XXXX/X
XX/X/XX
Screening
XXX.X
XXX.X
XXX.X
XXX.X
Re-screening#
XXX.X
XXX.X
XXX.X
XXX.X
Month 24
XXX.X
XXX.X
XXX.X
XXX.X
Month 36
XXX.X
XXX.X
XXX.X
XXX.X
EOP TFR
XXX.X
XXX.X
XXX.X
XXX.X


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Protocol No CAMN107AIC0
Listing 16.2.6-6.4.1 Ph+ by HIS– LSC sub-study Full Analysis Set
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native;
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
# Baseline value, latest available valid evaluation between Screening and Rescreening.
Country/ Center/ 
Patient/ Arm
Age/ 
Sex/ 
Race
Time
point
CD34+/CD38+
(Percentage 
of Ph+)
CD34+/CD38-
(Percentage of 
Ph+)
Immunopheno-
typically
Aberrant
CD34+ cells 
(Percentage 
of Ph+)
Immunopheno-
typically 
aberrant CD34 
negative 
cells 
(Percentage 
of Ph+)
XXX/0XXX/0XXXX/X
XX/X/XX
Screening#
Positive 
(xx.x%)
Negative 
Missing
Missing
Month 24
Positive
(xx.x%)
Negative
Positive
(xx.x%)
Positive
(xx.x%)
Month 36
Positive
(xx.x%)
Negative
Negative
Negative
EOP TFR
XXX.X
XXX.X
XXX.X
XXX.X
XXX/0XXX/0XXXX/X
XX/X/XX
Screening
Negative
Not Evaluable
Positive
(xx.x%)
Positive
(xx.x%)
Re-screening#
Negative
Not Evaluable
Positive
(xx.x%)
Positive
(xx.x%)
Month 24
Positive
(xx.x%)
Negative
Negative
Negative
Month 36
Positive
(xx.x%)
Positive
(xx.x%)
Negative
Negative
EOP TFR
XXX.X
XXX.X
XXX.X
XXX.X


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Protocol No CAMN107AIC0
Listing 16.2.6-6.5.1 BCR-ABL by RT-PCR– LSC sub-study Full Analysis Set
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native;
N: Native Hawaiian or other Pacific Islander; UK: Unknown; O: Other. 
# Baseline value, latest available valid evaluation between Screening and Rescreening.
Country/ Center/ 
Patient/ Arm
Age/ 
Sex/ 
Race
Time
point
CD34+/CD38+
CD34+/CD38-
Immunopheno-
typically
Aberrant
CD34+ cells
Immunopheno-
typically 
aberrant CD34 
negative 
cells
XXX/0XXX/0XXXX/X
XX/X/XX
Screening#
Positive
Negative
Missing
Missing
Month 24
Positive
Negative
Positive
Positive
Month 36
Positive
Negative
Negative
Negative
EOP TFR
XXX.X
XXX.X
XXX.X
XXX.X
XXX/0XXX/0XXXX/X
XX/X/XX
Screening
Negative
Not Evaluable
Positive
Positive
Re-screening#
Negative
Not Evaluable
Positive
Positive
Month 24
Positive
Negative
Negative
Negative
Month 36
Positive
Positive
Negative
Negative
EOP TFR
XXX.X
XXX.X
XXX.X
XXX.X


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Section 16.2.7 – Adverse event listings
Listing 16.2.7-1.1 All adverse events – Full Analysis Set
Country/ Center/ 
Patient/ Arm
Age/ Sex/ 
Race
Adverse Event Verbatim/
Abbreviated System organ 
class/ Preferred term
Start 
date/day      
End 
date/day     
Dur. 
(days)
Phase
Grade/SAE/ Relation/ 
Action taken  
XXX/0XXX/0XXXX/X
XX/X/XX
XXXXX/SOCXXXXX/PTXXXXX
DDMMMYYYY/X^
DDMMMYYYY/X
XX
IND/CON
S
G0-5/No/NS-S/A0-5
XXX/0XXX/0XXXX/X
XX/X/XX
XXXXX/SOCXXXXX/PTXXXXX
DDMMMYYYY/X^
DDMMMYYYY/X
XX
TFR
G0-5/Yes/NS-S/A0-5
XXX/0XXX/0XXXX/X
XX/X/XX
XXXXX/SOCXXXXX/PTXXXXX
DDMMMYYYY/X*
DDMMMYYYY/X
XX
RE-TRT
G0-5/No/NS-S/A0-5
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.- M: Male; F: Female; W: White; B: Black or African American; 
A: Asian; AI: American Indian or Alaska Native; N: Nat. Hawaiian or other Pac. Isl.; UK: Unknown; O: Other.
Day is relative to the first day of Treat. (day 1). Relationship to study drug: NS=Not suspected, S=Suspected.
Action taken: A0=No action taken; A1=Study drug dosage adj./temp. inter.; A2=Study drug perm. Discount. due to 
this AE; A3=Concomitant med. taken; A4=Non-drug therapy given; A5=Hosp./Prolonged hosp.
Phase: IND/CONS = ind./Cons. phase, TFR=treat. free remission phase and RE-TRT=re-treat. phase.
* Event occurred more than 30 days after last study treatment exposure date. 
^ Event occurred between patient’s informed consent date and the day before first dose of study medication.
@ For patient #
 death occurred during Survival follow-up.
<<Programming note: Abbreviated system organ class to be used for the listings i.e. removing the term disorder and 
conditions:
"NEOPLASMS"; "RESPIRATORY";   "BLOOD"; "GI"; "GENERAL"; "INFECTIONS"; "INJURIES"; "MUSCULOSKELETAL"; "NERVOUS"; "RENAL"; 
"REPRODUCTIVE SYSTEM"; "SKIN"; "SURGICAL AND MEDICAL"; "METABOLISM"; "IMMUNE".>> 
Add the following text in the main body of the Listing’s last page:
- Patient 
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported as disc. 
Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
- For patient #
AE “PHLEGMON FOOT - BIG TOE RIGHT” is reported as PT “Cellulitis” in the AE listing while it is 
reported as PT “Osteoarthritis” in the SAE listing. PT for the same AE has been wrongly decoded and reconciliation was not 
requiring a perfect match of the PT. 
Add following footnote at the end of last page: 
- For patient #
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.


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Listing 16.2.7-2.1 Serious adverse events Full Analysis Set
Country/
Center/ 
Patient/
Arm
Age/
Sex/
Race
Adverse Event Verbatim/
Abbreviated System organ class/ 
Preferred term
Start 
date/
day
End 
date/
day
Duration 
(days)
Gradfe/
Relation/
Action 
taken
____________________________________________________________________________________________________________________________
/X
    Verbatim/Ab SOCxxxxxx / PTxxxxxxxxxxx     16JUL2005/2    27JUL2005/13  12    G1/NS/A0 
    
    Verbatim/Ab SOCxxxxxx / PTxxxxxxxxxxx     18JUL2005/4*   27JUL2005/13  10    G1/S/A3,5
/X 
    Verbatim/Ab SOCxxxxxx / PTxxxxxxxxxxx     16JUL2005/-1^  27JUL2005/13  12    G1/NS/A0 
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized. Relationship to study drug: NS=Not suspected, S=Suspected.                               
- Action taken: A0=No action taken, A1=Study drug dosage adjusted/temp. inter., A2=Study drug perm. discont.
due to this AE, A3=Concomitant medication taken, A4=Non-drug therapy given, A5=Hospitalization /Prolonged
hospitalization. Day is relative to the first day of treatment (day 1). * Event occurred during the follow-up,
i.e. more than 30 days after last study treatment exposure date. ^ Event occurred between patient’s informed
consent date and the day before first dose of study medication. @ For patient #
 death occurred during
Survival FU. For patient #
 AE “PHLEGMON FOOT – BIG TOE RIGHT” is reported as PT “Cellulitis” in 
the AE listing while it is reported as PT “Osteoarthritis” in the SAE listing. PT for the same AE has been 
wrongly decoded and reconciliation was not requiring a perfect match of the PT.
<<Programming note: Abbreviated system organ class to be used for the listings i.e. removing the term disorder and 
conditions:
"NEOPLASMS"; "RESPIRATORY";   "BLOOD"; "GI"; "GENERAL"; "INFECTIONS"; "INJURIES"; "MUSCULOSKELETAL"; "NERVOUS"; "RENAL"; 
"REPRODUCTIVE SYSTEM"; "SKIN"; "SURGICAL AND MEDICAL"; "METABOLISM"; "IMMUNE".>> 
Add following footn
d of last page: 
- For patient #
, due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.


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Listing 16.2.7-2.2 Adverse events leading to study drug discontinuation – Full Analysis Set
<<Programming note: Same shell as serious adverse events listing (listing 16.2.7-2.1) but subset on AEs marked as leading to 
study drug discontinuation.>>
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized. Relationship to study drug: NS=Not suspected, S=Suspected
- Action taken: A0=No action taken, A1=Study drug dosage adjusted/temporarily interrupted, A2=Study drug 
permanently discontinued due to this AE, A3=Concomitant medication taken, A4=Non-drug therapy given, 
A5=Hospitalization/Prolonged hospitalization. Day is relative to the first day of treatment (day 1).
* event occurred during the follow-up, i.e. more than 30 days after last study treatment exposure date.
^ Εvent occurred between patient’s informed consent date and the day before first dose of study medication.
- Patient #
 reported as disc. Ind/Cons phase due to AE “Blast Crisis”- G2, should have been reported
as disc. Ind/Cons phase due to Disease Progression, progression to Blast Crisis, as per Prot.
<<Programming note: Abbreviated system organ class to be used for the listings i.e. removing the term disorder and 
conditions:
"NEOPLASMS"; "RESPIRATORY";   "BLOOD"; "GI"; "GENERAL"; "INFECTIONS"; "INJURIES"; "MUSCULOSKELETAL"; "NERVOUS"; "RENAL"; 
"REPRODUCTIVE SYSTEM"; "SKIN"; "SURGICAL AND MEDICAL"; "METABOLISM"; "IMMUNE".>> 
Add following footnote at the end of last page: 
- For patient #
 due to reconciliation discrepancies, safety database reported AE term “Endometriosis” as a SAE, 
while in clinical database this AE was not recorded as an SAE.


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Listing 16.2.7-2.3 Adverse events of interest – Full Analysis Set
<<Programming note: Same shell as serious adverse events listing (listing 16.2.7-2.1) but subset on AEs marked as Adverse 
Events of Interest.>>
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- Relationship to study drug: NS=Not suspected, S=Suspected.
- Action taken: A0=No action taken, A1=Study drug dosage adjusted/temporarily interrupted, A2=Study drug 
permanently discontinued due to this AE, A3=Concomitant medication taken, A4=Non-drug therapy given, 
A5=Hospitalization/Prolonged hospitalization.
- Day is relative to the first day of treatment (day 1)
* Εvent occurred during the follow-up, i.e. more than 30 days after last study treatment exposure date. 
^ Εvent occurred between patient’s informed consent date and the day before first dose of study medication.
<<Programming note: Abbreviated system organ class to be used for the listings i.e. removing the term disorder and 
conditions:
"NEOPLASMS"; "RESPIRATORY";   "BLOOD"; "GI"; "GENERAL"; "INFECTIONS"; "INJURIES"; "MUSCULOSKELETAL"; "NERVOUS"; "RENAL"; 
"REPRODUCTIVE SYSTEM"; "SKIN"; "SURGICAL AND MEDICAL"; "METABOLISM"; "IMMUNE".>> 


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Listing 16.2.7-3.1 CV risk factors, Nilotinib exposure, glucose and total cholesterol rates for patients with 
cardiac and vascular adverse events of interest, Full Analysis Set
Phase
Adverse Event Verbatim/ 
Abbreviated System organ class/ 
Preferred term                   
Start date/
End date
of AE (dur.)
Grade/
Relation/ 
Action taken
Fasting glucose 
(unit)/ Time 
between assessment 
and AE start date*
Total cholesterol 
(unit)/ Time between 
assessment and AE 
start date*
Country: xxx, Center: xxx, Patient: xxx, Arm: xx, Age: xxx, Sex: xxx, Race: xxx
CV risk factor at baseline: Very high/High/Moderate/Low
Values at baseline (units): fasting glucose: XX (xx), total cholesterol: XX (xx)
Treatment Administration: First Date: DDMMMYYYY, Last Date: DDMMMYYYY
IND/CONS
Verbatim/ Ab SOCxxxxxx/ 
PTxxxxxxxxxxx
DDMMYYYY/ 
DDMMYYYY (XX)
G1/NS/A0
xx
xx
TFR
Verbatim/Ab SOCxxxxxx / 
PTxxxxxxxxxxx
DDMMYYYY/ 
DDMMYYYY (XX)
G2/S/A2
xx
xx
RE-TRT
Verbatim/Ab SOCxxxxxx / 
PTxxxxxxxxxxx
DDMMYYYY/ 
DDMMYYYY (XX)
G2/S/A2
xx
xx
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- Phase: IND/CONS = induction/consolidation phase, TFR=treatment free remission phase 
and RE-TRT=re-treatment phase.
- Relationship to study drug: NS=Not suspected, S=Suspected
- Action taken: A0=No action taken, A1=Study drug dosage adjusted/temporarily interrupted, A2=Study drug 
permanently discontinued due to this AE, A3=Concomitant medication taken, A4=Non-drug therapy given, 
A5=Hospitalization/Prolonged hospitalization.
- Day is relative to the first day of treatment (day 1).
* The last available assessment before or at date of start of the event is considered.
<<Programming note: Selected AE with Abbreviated system organ class equal to ‘Cardiac disorders’ or ‘Vascular disorders’ and 
CVEs not empty. Relative line of treatment and laboratory assessments should be flag with REC1N [derived.a_ aev].
Adverse Event Verbatim/…: AEVNAM1AX/ ABBR_SOC/ PT_TXTX [derived.a_ aev]
Start date of AE/ day: AEVSTT1D/ AEDAY_1N [derived.a_ aev]
End date of AE/ day: AEVEND1D/ AEEND_1N [derived.a_ aev]
AE dur: AEDUR_1N [derived.a_ aev]
Grade/...: AEVGRD2C/ AEVSMR2C/ ACNTAKC [derived.a_ aev]
Fasting glucose (unit)/ Time between assessment and AE start date 
Total cholesterol (unit)/ Time between assessment and AE start date >>


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Listing 16.2.7-3.2 Cardiac and vascular adverse events of interest, Full Analysis Set
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- Phase: IND/CONS = induction/consolidation phase, TFR=treatment free remission phase and RE-TRT=re-treatment phase.
- IHD: Ischemic heart disease, PAOD: Peripheral arterial occlusive disease, ICE: Ischemic cerebrovascular events
- Relationship to study drug: NS=Not suspected, S=Suspected
- Action taken: A0=No action taken, A1=Study drug dosage adjusted/temporarily interrupted, A2=Study drug permanently 
discontinued due to this AE, A3=Concomitant medication taken, A4=Non-drug therapy given, A5=Hospitalization/Prolonged 
hospitalization
- Day is relative to the first day of treatment (day 1).
<<Programming note: Selected AE with Abbreviated system organ class equal to ‘Cardiac disorders’ or ‘Vascular disorders’and 
CVEs not empty
Total study period.
Treatment Administration: First Date: datepart(STTEXP1O), Last Date: datepart(ENDEXP1O) [derived.a_ dar]
Adverse Event Abbreviated System organ class: ABBR_SOC [derived.a_ aev]
Adverse Event Verbatim: AEVNAM1AX [derived.a_ aev]
Adverse Event Preferred term: PT_TXTX [derived.a_ aev]
CVEs: AEVSG1/ AEVSG2/ AEVSG3/AEVSG4
Phase
Adverse 
Event 
Abbrevia
ted 
System 
organ 
class
Adverse 
Event 
Verbatim
Adverse 
Event 
Preferred 
term
CVEs
Start date
of AE (day)
End date of AE 
(day)
AE
Dur.
Grade/
Relation/ 
Action taken
Country: xxx, Center: xxx, Patient: xxx, Arm: xx
Age: xxx, Sex: xxx, Race: xxx
Treatment Administration: First Date: DDMMMYYYY, Last Date: DDMMMYYYY
IND/CONS
Ab 
SOCxxxxx
x
Verbatim
PTxxxxxxxxxxx
IHD/PAOD/ICE/Others
DDMMMYYYY (XX)
DDMMMYYYY (XX)
XX
G1/NS/A0
Ab 
SOCxxxxx
x
Verbatim
PTxxxxxxxxxxx
IHD/PAOD/ICE/Others
DDMMMYYYY (XX)
DDMMMYYYY (XX)
XX
G2/S/A2


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Start date of AE/ day: AEVSTT1D/ AEDAY_1N [derived.a_ aev]
End date of AE/ day: AEVEND1D/ AEEND_1N [derived.a_ aev]
AE dur: AEDUR_1N [derived.a_ aev], Grade/...: AEVGRD2C/ AEVSMR2C/ ACNTAKC [derived.a_ aev]>>


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Listing 16.2.7-3.3 Outcomes and subsequent concomitant medications for patients with cardiac adverse events 
of interest, Full Analysis Set
Concomitant medications*
Phase
Date of first 
(cardiac event/ 
day
First cardiac event 
Verbatim/ Abbreviated 
System organ class/ 
Preferred term
Number of 
cardiac 
events
Date of study
discontinuatio
n/ day
Reason for 
study 
discontinuat
ion
Preferred 
term/ 
Verbatim / 
Indi
cati
on
Start date (day)
Country: xxx, Center: xxx, Patient: xxx, Arm:xx
Age: xxx, Sex: xxx, Race: xxx
Treatment Administration: First Date: DDMMMYYYY, Last Date: DDMMMYYYY
Date of last contact (day): DDMMMYYYY (XX)
IND/CONS
DDMMMYYYY/ XX
SOCxxxxxx/ Verbatim/ 
PTxxxxxxxx
XX
DDMMMYYYY/ XX
xxxxxx
PTXXXXX/
XXXXX
XXXX
DDMMMYYYY (XX)
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- Phase: IND/CONS = induction/consolidation phase, TFR=treatment free remission phase and RE-TRT=re-treatment phase.
- Day is relative to the first day of treatment (day 1).
- * Concomitant medications after the date of start of the first event where the indication is related to cardiovascular 
diseases. If the date of start of the first event is missing or incomplete then all concomitant medications after day 1 are 
displayed.
<<Programming note: Selected AE with Abbreviated system organ class equal to ‘Cardiac disorders’ and CVEs not empty
Treatment Administration: First Date: datepart(STTEXP1O), Last Date: datepart(ENDEXP1O) [derived.a_ dar]
Date of last contact: max(datepart(VIS_1O))/ DYVIS_1N [derived.a_vis]
Start date of AE/ day: AEVSTT1D/ AEVEND1D [derived.a_ aev]
Number of cardiac events: count (CARDEVT)
Date of Study discontinuation/ day: VIS1D / DYVIS_1N [derived.a_cmp]
Reason for study discontinuation: DCNRSN1C [derived.a_cmp]
Concomitant medications: where INDCVFL = 1 [derived.a_cmdatc]
Preferred term/ Verbatim : PT_TXT/ ATC_TXT
Indication: CMDRSN1A
Start date (day): CMDSTT1D/ CMDAY_1N 
>>


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Listing 16.2.7-3.4 Outcomes and subsequent concomitant medications for patients with vascular adverse 
events of interest, Full Analysis Set
Concomitant medications*
Phase
Date of 
first 
vascular 
event / day
First vascular event 
Abbreviated System organ 
class/ Verbatim/
Preferred term
Number of 
vascular 
events
Date of study 
discontinuatio
n/ day
Reason for 
study 
discontinuat
ion
Preferred 
term/ 
Verbatim / 
Indication
Start 
date (day)
Country: xxx, Center: xxx, Patient: xxx, Arm: xx
Age: xxx, Sex: xxx, Race: xxx
Treatment Administration: First Date: DDMMMYYYY, Last Date: DDMMMYYYY
Date of last contact (day): DDMMMYYYY (XX)
Phase
DDMMMYYYY
/ XX
SOCxxxxxx/ Verbatim/ 
PTxxxxxxxx
XX
DDMMMYYYY/ XX
xxxxxx
PTXXXXX/
XXXXX
XXXX
DDMMMYYYY 
(XX)
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- Phase of the event: IND/CONS = induction/consolidation phase, TFR=Treatment free remission phase and RE-TRT=Re-treatment 
phase.
- Day is relative to the first day of each phase (day 1)
- * Concomitant medications after the date of start of the first event where the indication is related to cardiovascular 
diseases. If the date of start of the first event is missing or incomplete then all concomitant medications after day 1 are 
displayed.
<<Programming note: Selected AE with Abbreviated system organ class equal to ‘Vascular disorders’ and CVEs not empty
Treatment Administration: First Date: datepart(STTEXP1O), Last Date: datepart(ENDEXP1O) [derived.a_ dar]
Date of last contact: max(datepart(VIS_1O))/ DYVIS_1N [derived.a_vis]
Start date of AE/ day: AEVSTT1D/ AEVEND1D [derived.a_ aev]
Number of vascular events: count (VASCEVT)
Date of Study discontinuation/ day: VIS1D / DYVIS_1N [derived.a_cmp]
Reason for study discontinuation: DCNRSN1C [derived.a_cmp]
Concomitant medications: where INDCVFL = 1 [derived.a_cmdatc]
Preferred term/ Verbatim : PT_TXT/ ATC_TXT
Indication: CMDRSN1A
Start date (day): CMDSTT1D/ CMDAY_1N 
>>


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Section 16.2.8 – Laboratory measurements
Listing 16.2.8-1.1 Hematology laboratory values and normal ranges – Full Analysis Set
Country/ Center/ 
Patient/ Arm
Age/ 
Sex/ 
Race
Phase/ Sample 
date/ Day
Test
Value         
(SI Unit)
Normal 
Range
Grade
XXX/0XXX/0XXXX/X
XX/X/XX
IND/CONS1/CONS2/
TFR/RE-TRT 
DDMMMYYYY/XX
Hemoglobin
XX (LB/%)
L/N/H
Gx
Platelets
XX (LB/%)
L/N/H
Gx
WBC
XX (LB/%)
L/N/H
Gx
Absolute Neutrophils/ Neutrophils
XX (LB/%)
L/N/H
Gx
Absolute Lymphocytes/ Lymphocytes
XX (LB/%)
L/N/H
Gx
Absolute Eosinophils/ Eosinophils
XX (LB/%)
L/N/H
Absolute Basophils/ Basophils
XX (LB/%)
L/N/H
Absolute Monocytes/ Monocytes
XX (LB/%)
L/N/H
Absolute Promyelocytes/ Promyelocytes
XX (LB/%)
L/N/H
Absolute Myelocytes/ Myelocytes
XX (LB/%)
L/N/H
Absolute Metamyelocytes/ Metamyelocytes
XX (LB/%)
L/N/H
Absolute Blasts/ Blasts
XX (LB/%)
L/N/H
Absolute Other/ Other
XXX
XX (LB/%)
L/N/H
Gx
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Phase: IND=ind. phase (0-12 months), CONS1 = pre-rand. cons. phase (12-24 months), CONS2 = post-rand. cons. phase (ARM 
2)(24–36 months), TFR=treatment free remission phase and RE-TRT=re-treatment phase.
- L/H denotes a value below/above normal range, N denotes normal.
- Gx denotes an abnormal high value meeting toxicity CTCAE grading criteria and G-x an abnormal low value according to 
toxicity CTCAE grading. Day is relative to the first day of treatment (day 1).
“Note for programming: When absolute and percentage value are provided, given both
Grade are to display only for laboratory tests where CTCAE grades are defined”


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Listing 16.2.8-2.1 Biochemistry laboratory values and normal ranges – Full Analysis Set
Country/ 
Center/ 
Patient/ Arm
Age/ 
Sex/ 
Race
Phase/ Sample 
date/ Day
Test
Value          
(SI Unit)
Normal 
Range
Grade
XXX/0XXX/0XXXX/
X
XX/X/XX
IND/CONS1/ 
CONS2/TFR/RE-
TRT 
DDMMMYYYY/XX
Creatine
XX (LB/%)
L/N/H
Gx
Hypoglycemia
XX (LB/%)
L/N/H
Gx
Hyperglycemia
XX (LB/%)
L/N/H
Gx
Total Cholesterol
XX (LB/%)
L/N/H
Gx
HDL
XX (LB)
L/N/H
LDL
XX (LB)
L/N/H
Triglycerides
XX (LB/%)
L/N/H
Gx
Total bilirubin
XX (LB/%)
L/N/H
Gx
Direct bilirubin
XX (LB/%)
L/N/H
Gx
Indirect bilirubin
XX (LB/%)
L/N/H
Gx
AST/SGOT
XX (LB/%)
L/N/H
Gx
ALT/SGPT
XX (LB/%)
L/N/H
Gx
LDH
XX (LB)
L/N/H
Hyponatremia
XX (LB/%)
L/N/H
Gx
Hypernatremia
XX (LB/%)
L/N/H
Gx
Hypocalcemia
XX (LB/%)
L/N/H
Gx
Hypercalcemia
XX (LB/%)
L/N/H
Gx
Hypokalemia
XX (LB/%)
L/N/H
Gx
Hyperkalemia
XX (LB/%)
L/N/H
Gx
Hypomagnesemia
XX (LB/%)
L/N/H
Gx
Hypermagnesemia
XX (LB/%)
L/N/H
Gx
Phosphorus
XX (LB/%)
L/N/H
Gx
Lipase
XX (LB/%)
L/N/H
Gx


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Amylase
XX (LB/%)
L/N/H
Gx
HbA1C
  XX (LB)
L/N/H
Alkaline Phosphatase Increase
XX (LB/%)
L/N/H
Gx
Hypoalbuminemia
XX (LB/%)
L/N/H
Gx
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Phase: IND = ind. phase (0-12 months), CONS1 = pre-rand. cons., CONS2 = post-rand.n cons. phase (ARM 2)(24–36 months) , 
TFR=treatment free remission phase, RE-TRT=re-treatment phase.
- L/H denotes a value below/above normal range, N denotes normal range.
- Gx denotes an abnormal high value meeting toxicity CTCAE grading criteria and G-x an abnormal low value according to 
toxicity CTCAE grading. Day is relative to the first day of treatment (day 1).
“Note for programming: Grade will be display only for laboratory tests where CTCAE grades are defined”


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Protocol No CAMN107AIC0
Listing 16.2.8-3.1 Hematological data and molecular response in patients with absolute blasts higher than
normal ranges, Full Analysis Set
Phase/    
Time-Windows/
Visit/       
Date of visit
% 
Blasts 
(range)
% 
Blasts in 
bone 
marrow
% 
Promye
locytes
(range)
% 
Basophils
(range)
%
Myelocytes
(range)
%
Meta-
myelocytes
(range)
Platelets 
10E9/L
WBC 
10E9/L
% 
BCR-ABL
/ABL
(IS)
Derived 
MR
Derived 
loss of 
MMR or 
MR 4.0
ARM: x, Country: xxx, Center: xxx, Patient: xxx, Age: xxx, Sex: xxx, Race: xxx
Treatment Administration: First Date: DDMMMYYYY, Last Date: DDMMMYYYY 
IND /M3/V1-M3
/DDMMMYYYY
XX 
(L/N/H)
XX 
XX 
(L/N/H)
XX 
(L/N/H)
XX 
(L/N/H)
XX 
(L/N/H)
XX
XX
XX
<3
IND/M6/UNSCH
/DDMMMYYYY
…
XX 
(L/N/H)
XX 
XX
(L/N/H)
XX 
(L/N/H)
XX 
(L/N/H)
XX 
(L/N/H)
XX
XX
XX
4.5
TFR/M6/UNSCH
/DDMMMYYYY
XX 
(L/N/H)
XX 
XX 
(L/N/H)
XX 
(L/N/H)
XX 
(L/N/H)
XX 
(L/N/H)
XX
XX
XX
<3
Loss of 
MMR
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- L/N/H denotes categories defined by normal ranges.
- BASE=Baseline; SCR=Screening; RANDO = Randomization; EOP = End Of Phase; UNSCH = Unscheduled visit; IND = induction phase
(0-12 months), CONS1 = pre-randomization consolidation phase, CONS2 = post-randomization consolidation phase (ARM 2)(24–36 
months), TFR=Treatment free remission phase and RE-TRT=Re-treatment phase.- PCR assessments, laboratory assessments and bone 
marrow assessments are merged together by visit number, visit date and visit name.
- When patients are in molecular response 4.5 then Molecular Response (MR) is equal to 4.5, if patients are in molecular 
response 4.0 then MR is equal to 4, if patients are in major molecular response then MR is equal to 3, if none of those 
responses are defined but BCR-ABL (IS) ratio > 0.1 then MR is equal to <3.
<<Programming note: For each patient merge PCR data with haematological data by time-point and visit. If there are several 
unscheduled visits in a same time-window then merge them by incremental order defined by chronology >>


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RAP Module 7.1
6-May-2021 (14:35)
Protocol No CAMN107AIC0
Listing 16.2.8-3.2 Hematological data and molecular response in patients with absolute metamyelocytes higher 
than normal ranges, Full Analysis Set
Phase/
Time-
Windows
/
Visit
% Blasts 
(range)
% 
Blasts 
in bone 
marrow
% 
Promye
Locytes
(range)
% 
Basophils
(range)
%
Myelocytes
(range)
%
Metamyelocytes
(range)
Platelets 
10E9/L
WBC 
10E9/L
% BCR-
ABL/ABL
(IS)
Molecular 
Response
Derived
ARM:x,  Country: xxx, Center: xxx, Patient: xxx, Age: xxx, Sex: xxx, Race: 
xxx
Treatment Administration: First Date: DDMMMYYYY, Last Date: DDMMMYYYY 
M3/ 
V1-M3
XX 
(L/N/H)
XX 
XX 
(L/N/H)
XX 
(L/N/H)
XX (L/N/H)
XX (L/N/H)
XX
XX
XX
<3
M6/ 
UNSCH
XX 
(L/N/H)
XX
XX 
(L/N/H)
XX 
(L/N/H)
XX (L/N/H)
XX (L/N/H)
XX
XX
XX
4.5
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- L/N/H denotes categories defined by normal ranges
- BASE=Baseline; SCR=Screening; RANDO = Randomization; EOP = End Of Phase; UNSCH = Unscheduled visit; IND = induction phase
(0-12 months), CONS1 = pre-randomization consolidation phase (0-24 months), CONS2 = post-randomization consolidation phase 
(ARM 2)(24–36 months), TFR=Treatment free remission phase and RE-TRT=Re-treatment phase.
- PCR assessments, laboratory assessments and bone marrow assessments are merged together by visit number, visit date and 
visit name
- When patients are in molecular response 4.5 then Molecular Response is equal to 4.5, if patients are in molecular response 
4.0 then Molecular Response is equal to 4, if patients are in major molecular response then Molecular Response is equal to 3, 
if none of those responses are defined but BCR-ABL (IS) ratio > 0.1 then Molecular Response is equal to <3.
<<Programming note: For each patient merge PCR data with haematological data by time-point and visit. If there are several 
unscheduled visit in a time-window then merge them by incremental order defined by chronology >>


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RAP Module 7.1
6-May-2021 (14:35)
Protocol No CAMN107AIC0
Section 16.2.9 – Vital signs, physical findings and other observations related to safety listings
Listing 16.2.9-1.1    Vital signs – Full Analysis Set
Country/ Center/ 
Patient/ Arm
Age/Sex/Race
Cardiovascular
Event (type)
Visit
Weight
(kg)
Body 
temperature 
(C)
Sitting 
Pulse
(bpm)
Sitting 
Blood pressure
Systolic/Diastolic
(mmHg)
XXX/0XXX/0XXXX/1
XX/X/XX
Yes (IHD, ICE )
Screening
XX.X
XX.X
XX
XX.X / XX.X
Month 3
XX.X
XX.X
XX
XX.X / XX.X
Month 6
XX.X
XX.X
XX
XX.X / XX.X
Month 9
XX.X
XX.X
XX
XX.X / XX.X
...
...
...
...
...
Month 24
XX.X
XX.X
XX
XX.X / XX.X
XXX/0XXX/0XXXX/2
XX/X/XX
No
Screening
XX.X
XX.X
XX
XX.X / XX.X
...
...
...
...
...
Month 24
XX.X
XX.X
XX
XX.X / XX.X
...
...
...
...
...
Month 36
XX.X
XX.X
XX
XX.X / XX.X
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
-CVE categories: IHD: Ischemic heart disease, PAOD: Peripheral arterial occlusive disease, ICE: Ischemic cerebrovascular 
events), Others.


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RAP Module 7.1
6-May-2021 (14:35)
Protocol No CAMN107AIC0
Listing 16.2.9-2.1   Electrocardiograms – Full Analysis Set
Country/ Center/ 
Patient/ Arm
Age/Sex/Race
Phase
Date of ECG
QTcF interval 
(msec)
Clinically 
significant 
abnormalities 
present?
If clinically 
significant, 
specify
XXX/0XXX/0XXXX/X
XX/X/XX
IC
DDMMMYYYY
XX
Yes/No
XXXXXXXXX
IC
DDMMMYYYY
XX
Yes/No
XXXXXXXXX
Repeat for each assessment  
XXX/0XXX/0XXXX/X
XX/X/XX
IC
DDMMMYYYY
XX
Yes/No
XXXXXXXXX
IC
DDMMMYYYY
XX
Yes/No
XXXXXXXXX
Repeat for each assessment
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Phase: IND = induction phase (0-12 months), CONS1 = pre-randomization consolidation phase(0-24 months), CONS2 = post-
randomization consolidation phase (ARM 2)(24–36 months), TFR=treatment free remission phase and RE-TRT=re-treatment phase.
Listing 16.2.9-2.2   Echocardiography – Full Analysis Set
Country/ Center/ 
Patient/ Arm
Age/Sex/Race
Phase
Date of 
Echocardiography
LVEF 
(%)
Interpretation
If clinically 
significant, 
specify
XXX/0XXX/0XXXX/X
XX/X/XX
IC
DDMMMYYYY
XX
N/CI/CS
XXXXXXXXX
IC
DDMMMYYYY
XX
N/CI/CS
XXXXXXXXX
Repeat for each assessment
XXX/0XXX/0XXXX/X
XX/X/XX
IC
DDMMMYYYY
XX
N/CI/CS
XXXXXXXXX
IC
DDMMMYYYY
XX
N/CI/CS
XXXXXXXXX
Repeat for each assessment
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
ND: Not Done.
- Phase: IND = induction phase (0-12 months), CONS1 = pre-randomization consolidation phase (0-24 months), CONS2 = post-
randomization consolidation phase (ARM 2)(24–36 months), TFR=treatment free remission phase and RE-TRT=re-treatment phase.
- Interpretation: N=Normal, CI=Clinically insignificant abnormality, CS=Clinically significant abnormality.


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RAP Module 7.1
6-May-2021 (14:35)
Protocol No CAMN107AIC0
Listing 16.2.9-3.1  Concomitant medications – Full Analysis Set
Country/ 
Center/ 
Patient/ Arm
Age/ Sex/ 
Race
Preferred 
term/ Verbatim
ATC 
level 2
Indication
Start/End 
dates
Phase
Route of 
administration
Dose (units)/ 
Frequency
XXX/0XXX/0XXXX
/X
XX/X/XX
PTXXXXX/XXXXX
XXXXX
XXXXX
DDMMMYYYY
/ 
DDMMMYYYY
IND 
XXXXX
XX (X)/ XX
XXX/0XXX/0XXXX
/X
XX/X/XX
PTXXXXX/XXXXX
XXXXX
XXXXX
DDMMMYYYY
/ 
DDMMMYYYY
RE-TRT
XXXXX
XX (X)/ XX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Phase: IND = induction phase, CONS1 = pre-randomization consolidation phase (0-24 months, CONS2 = post-randomization 
consolidation phase (ARM 2)(24–36 months), TFR=treatment free remission phase and RE-TRT=re-treatment phase.
Listing 16.2.9- 3.2  Prohibited concomitant medications – Full Analysis Set
Country/ 
Center/ 
Patient/ Arm
Age/ Sex/ 
Race
Preferred 
term/ Verbatim
ATC 
level 2
Indication
Start/End 
dates
Phase
Route of 
administration
Dose (units)/ 
Frequency
XXX/0XXX/0XXXX
/X
XX/X/XX
PTXXXXX/XXXXX
XXXXX
XXXXX
DDMMMYYYY
/ 
DDMMMYYYY
CONS1 
XXXXX
XX (X)/ XX
XXX/0XXX/0XXXX
/X
XX/X/XX
PTXXXXX/XXXXX
XXXXX
XXXXX
DDMMMYYYY
/ 
DDMMMYYYY
CONS2
XXXXX
XX (X)/ XX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
- Phase: CONS1 = pre-randomization consolidation phase (0-24 months, CONS2 = post-randomization consolidation phase (ARM 
2)(24–36 months).


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RAP Module 7.1
6-May-2021 (14:35)
Protocol No CAMN107AIC0
Listing 16.2.9-4.1     Prior Imatinib therapy– Full Analysis Set
Country/ 
Center/ 
Patient/ Arm
Age/ Sex/ 
Race
Start/End 
dates
Route of 
administration
Dose (units)/ 
Frequency
Therapy 
type
Reason for 
discontinuat
ion
XXX/0XXX/0XXXX
/X
XX/X/XX
DDMMMYYYY/ 
DDMMMYYYY
XXXXX
XX (X)/ XX
Chemotherapy
xxxxxxxxxxx
XXX/0XXX/0XXXX
/X
XX/X/XX
DDMMMYYYY/ 
DDMMMYYYY
XXXXX
XX (X)/ XX
Targeted 
therapy
xxxxxxxxxxxx
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
Listing 16.2.9-4.2     Prior antineoplastic therapy, other than Imatinib – Full Analysis Set
Country/ 
Center/ 
Patient/ Arm
Age/ Sex/ 
Race
Preferred 
term/ 
Verbatim
ATC 
level 
2
Start/End 
dates
Route of 
administ
ration
Dose (units)/ 
Frequency
Therapy 
type
Reason for 
discontinuation
XXX/0XXX/0XXX
X/X
XX/X/XX
PTXXXXX/XXXXX
XXXXX
DDMMMYYYY/ 
DDMMMYYYY
XXXXX
XX (X)/ XX
Chemotherapy
xxxxxxxxxxx
XXX/0XXX/0XXX
X/X
XX/X/XX
PTXXXXX/XXXXX
XXXXX
DDMMMYYYY/ 
DDMMMYYYY
XXXXX
XX (X)/ XX
Targeted 
therapy
xxxxxxxxxxxx
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.


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Page 454
RAP Module 7.1
6-May-2021 (14:35)
Protocol No CAMN107AIC0
Listing 16.2.9-5.1    Survival follow-up– Full Analysis set  
If no
If yes 
or Lost 
to 
follow-
up
If receiving
any TKI 
treatmen, 
Country/ 
Center/
Patient/ 
Arm
Age/ 
Sex/ 
Race
Visit
Is the 
Subjec
t
alive
Date
of
death
Princip
al
cause
of
Death
If
other
speci
fy
Last
date 
of 
contact
?
Did patient
undergo 
stem-cell
transplant 
/
Is the 
disease
progressing
to AP/BP ? 
Is the 
patient 
receivi
ng any 
TKI 
treatme
nt ?
Treatment
If 
other 
specify
XXX/0XXX/
0XXXX/X
XX/X/
XX
FU-Month 
3
Yes
Yes/No
Yes
Nilotinib
XXX/0XXX/
0XXXX/X
XX/X/
XX
FU-Month 
6
Yes
DDMMMYY
YY
Yes/No
No
...
XXX/0XXX/
0XXXX/X@
XX/X/
XX
FU-Month 
36
Yes
DDMMMYY
YY
Yes/No
Yes
Other
xxxxxxx
XXX/0XXX/
0XXXX/X
XX/X/
XX
FU-Month 
3
No
DDMMMYYYY
Study 
indicat
ion 
(CML)
...
XXX/0XXX/
0XXXX/X
XX/X/
XX
FU-Month 
3
No
DDMMMYYYY
Other
XXXXX
XXX
...
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
@ For patient #
death occurred during Survival follow-up.


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RAP Module 7.1
6-May-2021 (14:35)
Protocol No CAMN107AIC0
Listing 16.2.9-5.2    Safety follow-up– Full Analysis set  
Country/ Center/
Patient/ Arm
Age/ 
Sex/ 
Race
Safety follow
up performed
Date of 
clinical 
visit/ 
telephone 
call
In case of 
telephone call
Medical 
intervention 
necessary?
Date of 
Medical 
intervention
Reason for 
safety 
follow up
Not Performed
XXX/0XXX/0XXXX/X
XX/X/XX
During Clinical visit
DDMMMYYYY
XXX/0XXX/0XXXX/X@
XX/X/XX
During Telephone call
DDMMMYYYY
Yes
DDMMMYYYY
XXX/0XXX/0XXXX/X
XX/X/XX
No
XXXXXXXXXXXXX
- Arm: 1: Arm 1; 2: Arm 2; 3: Not Randomized.
- M: Male; F: Female; W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native 
Hawaiian or other Pacific Islander; UK: Unknown; O: Other.
@ For patient #
death occurred during Survival follow-up.


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RAP Module 7.1
6-May-2021 (14:35)
Protocol No CAMN107AIC0
Listing 16.2.9-6    Prior imatinib exposure – LSC sub-study Full Analysis Set
1: ARM 1; 2: ARM 2; 3: Not Randomized. M: Male; F: Female; 
W: White; B: Black or African American; A: Asian; AI: American Indian or Alaska Native; N: Native Hawaiian or other Pacific 
Islander; UK: Unknown; O: Other. 
Sokal score category: low risk (<0.8), intermediate risk (>=0.8-<=1.2) and high risk (>1.2).
Country/ 
Center/ 
Patient/ 
Arm
Age/ 
Sex/
Race
Prior 
Imatinib
intake
Duration 
of prior 
exposure
(months)
Duration 
of prior 
exposure 
category
(years)
Sokal 
Score
at 
diagnosis
Sokal 
Score category
at 
diagnosis 
XXX/0XXX/0XXXX/X
XX/X/XX
YES
xx.x
<2
xx.x
Low risk
XXX/0XXX/0XXXX/X
XX/X/XX
NO
xx.x
xx.x
Low risk
XXX/0XXX/0XXXX/X
XX/X/XX
YES
xx.x
>=2 - <5 
xx.x
High risk
XXX/0XXX/0XXXX/X
XX/X/XX
YES
xx.x
>=5
xx.x
Intermediate risk