A Phase 2, Randomized, Double-Blind, Placebo-controlled Study to Compare Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Best Supportive Care as Maintenance Therapy in Japanese Subjects With Acute Myeloid Leukemia in Complete Remission
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Phase 2, Randomized, Double-Blind, Placebo-controlled Study to Compare Efficacy and Safety of 
Oral Azacitidine plus Best Supportive Care versus Best Supportive Care as Maintenance Therapy in 
Japanese Subjects with Acute Myeloid Leukemia in Complete Remission 
 
NCT Number: NCT05197426 
Document Date (Date in which document was last revised): 27-Jun-2023 
 
 
 

Page:
1
Protocol Number:
CA055005
Date:
20-Aug-2021
Revised Date:
27-Jun-2023
CLINICAL PROTOCOL CA055005
A Phase 2, Randomized, Double-Blind, Placebo-controlled Study to Compare Efficacy and 
Safety of Oral Azacitidine plus Best Supportive Care versus Best Supportive Care as 
Maintenance Therapy in Japanese Subjects with Acute Myeloid Leukemia in Complete 
Remission
Brief Title:
A Study of Oral Azacitidine or Placebo with Best Supportive Care as Maintenance Therapy in 
Japanese Subjects with Acute Myeloid Leukemia in Complete Remission
Protocol Amendment 02
Clinical Trial Physician - Medical Monitor
Bristol-Myers Squibb Company
1-2-1 Otemachi, Chiyoda-ku,
Tokyo, 100-0004, Japan
Phone 
email: 
Clinical Scientist
Bristol-Myers Squibb Company
1-2-1 Otemachi, Chiyoda-ku,
Tokyo, 100-0004, Japan
Phone 
email: 
24-hr Emergency Telephone Number
USA: 1-866-470-2267
International: +1-248-844-7390
Japan: 0120-113713
Bristol-Myers Squibb Company
Route 206 & Province Line Road
Lawrenceville, NJ 08543
1-2-1 Otemachi, Chiyoda-ku,
Tokyo, 100-0004, Japan
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CA055005
BMS-986345
Oral Azacitidine
Protocol Amendment No.: 02
Date: 27-Jun-2023
2
REGULATORY AGENCY IDENTIFIER NUMBER(S)
IND: NA
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. References to BMS in this protocol may apply to partners to which BMS 
has transferred obligations (eg, a Contract Research Organization [CRO]).  
© 2023 Bristol-Myers Squibb Company
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CA055005
BMS-986345
Oral Azacitidine
Protocol Amendment No.: 02
Date: 27-Jun-2023
3
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Protocol Amendment 
02
27-Jun-2023
The CA055-005 study amendment 02 reflects the recent 
changes of clinical practice in the treatment of newly 
diagnosed AML, that have impacted study feasibility and 
enrollment. The changes of amendment 02 includes 
revisions to the schedule of activities, risk assessment, 
exploratory objectives and endpoints, number of 
participants, intensive PK samples, and statistical 
considerations.
Administrative Letter
02
24-Oct-2022
Corrected misspelling
Administrative Letter
01
10-Oct-2022
Updated study personnel information
Protocol Amendment 
01
25-July-2022
Amendment 01for CA055055 includes addition of an 
Eastern Cooperative Oncology Group (ECOG) performance 
status as a new inclusion criterion. Additionally, updates are 
made to clarify the assessments to be performed at 
appropriate time points, improve alignment across protocol 
sections and establish consistency, and update contact 
information.
Original Protocol
21-Aug-2021
Not applicable
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BMS-986345
Oral Azacitidine
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02:
The CA055005 study amendment 02 reflects the recent changes of clinical practice in the treatment 
of newly diagnosed AML with improved access to allogeneic transplantation (including older 
patients), the approval of non-intensive induction regimen such as azacitidine venetoclax, and the 
use of more extensive consolidation regimens (3 and more cycles). This has impacted study 
feasibility and enrollment. The changes of amendment 02 include revisions to the number of 
participants, schedule of activities, risk assessment, exploratory objectives, references to number 
of intensive PK sampling, and statistical considerations. Additionally, the changes which were
previously updated by the administrative letters, have been incorporated into this amendment.
Other revisions, including to sections of the Protocol Summary, have been made to align the 
protocol with respect to these changes.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section 
Number & 
Title
Description of Change
Brief Rationale
Protocol 
Summary
Updated to reflect changes in the 
body of the protocol.
For consistency across the protocol.
Table 2-1: 
Screening 
Procedural 
Outline 
Table 2-2: On 
treatment 
Procedural
Outline 
Table 2-3: 
End-of-
treatment and 
Follow-up 
Procedural
Outline
Table 4-1:
Exploratory
Objectives and 
Endpoints
9.7
Biomarkers
Table 9.7-1:
Biomarker 
Severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2)
serology testing and exploratory
evaluation removed.
To align with the updated SARS-CoV-
2 protocol guidance document.
Protocol Amendment No.: 02
Date: 27-Jun-2023
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Oral Azacitidine
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section 
Number & 
Title
Description of Change
Brief Rationale
Sampling 
Schedule (All 
Participants)
10.4.4
Exploratory 
Endpoint(s)
Table 3.3.1-1:
Risk 
Assessment
Hypotheses for sample size 
calculation removed from Study 
Procedures, Study Design section.
To reflect change of statistical analysis 
plan.
Table 3.3.1-1:
Risk 
Assessment
Risk of small sample size and 
mitigation strategy were added.
Due to change in the number of 
participants.
5.1Overall 
Design Figure 
5.1-1: Study 
Design 
Schema
5.2 Number of 
Participants
10.2 Sample 
Size
Determination
Number of participants in total
was changed from 66 to 15. And
accordingly, the number of 
participants receiving CC-486 and 
the number of participants 
receiving placebo has changed.
Number of participants was modified 
based on change of enrollment plan.
Section 9.5 
Pharmacokine
tics
References to the number of 
participants undergoing intensive 
PK sampling were removed.
Due to change in the number of
participants.
10.1 Statistical 
Hypotheses
10.4.2
Primary 
Endpoint(s)
Hypothesis testing removed and a 
Cox proportional hazards model
was added.
To reflect change of statistical analysis 
plan.
10.1 Statistical 
Hypotheses
Timing of analysis of the primary 
endpoint was added.
To reflect change of statistical analysis 
plan.
10.2 Sample 
Size 
Determination
The threshold for the median RFS 
for placebo and expected median 
RFS for CC-486 were removed.
To reflect change of statistical analysis 
plan.
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BMS-986345
Oral Azacitidine
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section 
Number & 
Title
Description of Change
Brief Rationale
The hazard ratio based on the 
changed number of participants
was added.
All
Description
Minor edits and clarifications 
were made.
Minor, therefore have not been 
summarized.
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TABLE OF CONTENTS 
 
 
TITLE PAGE ................................................................................................................ 
 
DOCUMENT HISTORY .............................................................................................. 
 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02: ............................ 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02 ................ 
 
TABLE OF CONTENTS .............................................................................................. 
 
1 PROTOCOL SUMMARY ......................................................................................... 
 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
 
3 INTRODUCTION ..................................................................................................... 
 
3.1 Study Rationale ................................................................................................. 
 
3.2 Background ....................................................................................................... 
 
3.3 Benefit/Risk Assessment .................................................................................. 
 
3.3.1 Risk Assessment ....................................................................................... 
 
3.3.2 Benefit Assessment ................................................................................... 
 
3.3.3 Overall Benefit/Risk Conclusion .............................................................. 
 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
 
5 STUDY DESIGN....................................................................................................... 
 
5.1 Overall Design .................................................................................................. 
 
5.1.1 Data Monitoring Committee and Other Committees ............................... 
 
5.2 Number of Participants ..................................................................................... 
 
5.3 End of Study Definition .................................................................................... 
 
5.4 Scientific Rationale for Study Design............................................................... 
 
5.4.1 Participant Input Into Study Design ........................................................ 
 
5.5 Justification for Dose ........................................................................................ 
 
6 STUDY POPULATION ............................................................................................ 
 
6.1 Inclusion Criteria .............................................................................................. 
 
6.2 Exclusion Criteria ............................................................................................. 
 
6.3 Lifestyle Restrictions ........................................................................................ 
 
6.4 Screen Failures .................................................................................................. 
 
6.4.1 Retesting During Screening or Lead-in Period ....................................... 
 
7 STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ....................... 
 
7.1 Study Interventions Administered .................................................................... 
 
7.1.1 Best Supportive Care ............................................................................... 
 
7.2 Method of Study Intervention Assignment ....................................................... 
 
7.3 Blinding............................................................................................................. 
 
7.4 Dosage Modification ......................................................................................... 
 
7.4.1 Dose Modifications for Toxicity ............................................................... 
 
7.4.2 Dose and Schedule Adjustment in Participants with AML 
Relapse/Progression ................................................................................... 
 
7.4.3 Re-treatment Criteria ............................................................................... 
 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
 
7.6 Treatment Compliance ...................................................................................... 
 
7.7 Concomitant Therapy........................................................................................ 
 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
 
7.7.1.1 Permitted Concomitant Medications and Procedures .................... 
 
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CA055005
Oral Azacitidine
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7.7.1.2 Prohibited Concomitant Medications and Procedures .................. 
 
7.7.2 Other Restrictions and Precautions ......................................................... 
 
7.8 Continued Access to Study Intervention After the End of the Study ............... 
 
8 DISCONTINUATION CRITERIA ........................................................................... 
 
8.1 Discontinuation From Study Intervention ........................................................ 
 
8.1.1 Post-study Intervention Study Follow-up................................................. 
 
8.2 Discontinuation From the Study ....................................................................... 
 
8.2.1 Individual Discontinuation Criteria ........................................................ 
 
8.3 Lost to Follow-up .............................................................................................. 
 
9 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
 
9.1 Efficacy Assessments ........................................................................................ 
 
9.1.1 Efficacy Assessment for the Study ............................................................ 
 
9.1.2 Health-related Quality of Life .................................................................. 
 
9.2 Adverse Events ................................................................................................. 
 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
 
9.2.2 Method of Detecting AEs and SAEs ......................................................... 
 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
 
9.2.4 Regulatory Reporting Requirements for SAEs ......................................... 
 
9.2.5 Pregnancy ................................................................................................ 
 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
 
9.2.7 Potential Drug-induced Liver Injury ....................................................... 
 
9.2.8 Other Safety Considerations .................................................................... 
 
9.3 Overdose ........................................................................................................... 
 
9.4 Safety ................................................................................................................ 
 
9.4.1 Physical Examinations ............................................................................. 
 
9.4.2 Vital Signs ................................................................................................ 
 
9.4.3 Electrocardiograms ................................................................................. 
 
9.4.4 Clinical Safety Laboratory Assessments .................................................. 
 
9.4.5 Imaging Safety Assessment ...................................................................... 
 
9.5 Pharmacokinetics .............................................................................................. 
 
9.6 Genetics............................................................................................................. 
 
9.7 Biomarkers ........................................................................................................ 
 
9.8 Additional Research .......................................................................................... 
 
9.9 Health Economics OR Medical Resource Utilization and Health Economics . 
 
10 STATISTICAL CONSIDERATIONS .................................................................... 
 
10.1 Statistical Hypotheses ..................................................................................... 
 
10.2 Sample Size Determination ............................................................................. 
 
10.3 Analysis Sets ................................................................................................... 
 
10.4 Statistical Analyses ......................................................................................... 
 
10.4.1 General Considerations ......................................................................... 
 
10.4.2 Primary Endpoint(s) .............................................................................. 
 
10.4.3 Secondary Endpoint(s) ........................................................................... 
 
10.4.4 Exploratory Endpoint(s) ........................................................................ 
 
10.4.5 Other Safety Analysis ............................................................................. 
 
10.4.6 Other Analyses ....................................................................................... 
 
10.5 Interim Analyses ............................................................................................. 
 
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CA055005
Oral Azacitidine
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11 REFERENCES ........................................................................................................ 
 
12 APPENDICES ......................................................................................................... 
 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW-UP, AND REPORTING ....................................................................... 
 
APPENDIX 4 CONTRACEPTION REQUIREMENTS.............................................. 
 
APPENDIX 5 ECOG PERFORMANCE STATUS CRITERIA .................................. 
 
APPENDIX 6 INTERNATIONAL WORKING GROUP AML RESPONSE 
CRITERIA .............................................................................................................. 
 
APPENDIX 7 RECOMMENDATIONS FOR MANAGEMENT OF TREATMENT-
INDUCED DIARRHEA ......................................................................................... 
 
APPENDIX 8 FACIT-FATIGUE SCALE (VERSION 4) ........................................... 
 
APPENDIX 9 EQ-5D-5L HEALTH QUESTIONNAIRES ......................................... 
 
APPENDIX 10 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
................................................................................................................................. 
 
 
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CA055005
Oral Azacitidine
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CA055005
BMS-986345
Oral Azacitidine
1
PROTOCOL SUMMARY
Protocol Title:
A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Compare Efficacy and Safety 
of Oral Azacitidine plus Best Supportive Care versus Best Supportive Care as Maintenance 
Therapy in Japanese Subjects with Acute Myeloid Leukemia in Complete Remission
Brief Title:
A study of Oral Azacitidine or Placebo with Best Supportive Care as Maintenance Therapy in 
Japanese Subjects with Acute Myeloid Leukemia in Complete Remission
Rationale:
The standard treatment modality for acute myeloid leukemia (AML) is chemotherapy globally as 
well as in Japan. The therapeutic approaches are usually divided into two phases: induction of 
remission and post-remission (consolidation) therapy. A common induction regimen consists of 
cytarabine 100 mg/m2/day for 7 days combined with daunorubicin 60 to 90 mg/m2/day for 3 days, 
often referred to as the “7+3 protocol.” For post-remission chemotherapy, the same chemotherapy 
agent(s) used for remission induction is often repeated for one or more cycles, referred to as 
consolidation chemotherapy. When several courses of consolidation are given, despite achieving 
complete remission (CR), approximately 50% of younger (< 60 years old) and 80% to 90% of 
older patients will relapse, and most of these patients will die due to AML, with median survival 
from 3 to 12 months after relapse. For patients with relapsed AML, the duration of first CR is
strongly correlated with subsequent outcomes, with longer duration of first CR associated with 
better survival. Up to the present time, there has not been any successful maintenance therapy that 
has led to a benefit in prolonging survival for patients achieving CR after intensive chemotherapy. 
Therefore, an unmet medical need exists for maintaining a deeper level of remission over a longer 
duration in patients who achieve remission. Effective maintenance therapy for patients who attain 
remission with intensive chemotherapy may play a role in preventing relapse and prolonging 
overall survival (OS), especially in those ineligible for allogeneic hematopoietic stem cell 
transplantation.
CC-486 (oral azacitidine) was confirmed to show statistically significant prolongation of OS and 
relapse-free survival (RFS) in the maintenance setting in patients ≥ 55 years of age with AML, and 
in CR or complete remission with incomplete blood count recovery (CRi) after conventional 
induction chemotherapy with or without consolidation chemotherapy in Study CC-486-AML-001. 
CC-486 was already approved for the treatment of AML in the United States in September 2020, 
in Canada in January 2021, and in the European Union in June 2021.  CC-486 is recommended for 
the treatment of AML patients in complete remission as maintenance therapy regardless of age (< 
60 years or ≥ 60 years) per the National Comprehensive Cancer Network clinical practice guideline 
(Category 2B).
CA055005 is a bridging study to provide clinical data that will allow extrapolation of the CC-486-
AML-001 study data to Japan. This study is designed as a 2:1 randomization of CC-486 or placebo 
to assess the efficacy and safety of maintenance treatment with oral azacitidine in a cohort of 
Protocol Amendment No.: 02
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Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Japanese participants ≥ 55 years of age with AML and in CR/CRi after conventional induction 
chemotherapy with or without consolidation chemotherapy. The primary endpoint of RFS and 
secondary endpoints of OS, safety, pharmacokinetics (PK), and health-related quality of life 
(HRQoR) will be evaluated and allow for a comprehensive investigation of the efficacy, 
exposure/safety, and HRQoL appropriateness of clinical recommended dose for the Japanese 
population in comparison with the data from the Study CC-486-AML-001.
Objectives and Endpoints:
Objectives
Endpoints
Primary

To evaluate the efficacy of CC-486 as maintenance 
therapy by using RFS in Japanese participants with 
≥ 55 years with AML, who have achieved first CR
or CRi after induction with intensive chemotherapy 
with or without consolidation chemotherapy.

RFS
Secondary
To determine the effect of CC-486 as maintenance 
therapy on OS, time to relapse from CR/CRi, and 
time to discontinuation from treatment
To determine safety and tolerability
To determine PK
To determine the effect of CC-486 on HRQoL
OS
Time to relapse from CR/CRi
Time to discontinuation from treatment
Safety/tolerability (type, frequency, severity, and 
relationship of AEs to study treatments; physical 
examinations, vital signs; clinical laboratory 
evaluations, and concomitant medication/therapy)
PK parameters
Participant-reported outcomes utilizing the FACIT-
Fatigue Scale and the EQ-5D-5L
Abbreviations: AE, adverse event; AML, acute myeloid leukemia; CR, complete remission; CRi, complete remission 
with incomplete blood count recovery; DNA, deoxyribonucleic acid; EQ-5D-5L, EuroQol 5-dimension 5-level 
questionnaire; FACIT, Functional Assessment of Chronic Illness Therapy; HRQoL, health-related quality of life; OS, 
overall survival; PK, pharmacokinetic(s); RFS, relapse-free survival.
Overall Design:
This is a multicenter, placebo-controlled, Phase 2 study with a double-blind, randomized, 2:1 
group design in Japanese participants with de novo AML or AML secondary to prior diagnosis of 
MDS or CMML, aged ≥ 55 years, who are in first CR/CRi following induction therapy with or 
without consolidation chemotherapy.
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CA055005
BMS-986345
Oral Azacitidine
Number of Participants:
Approximately 15 participants will be randomized 2:1 to receive CC-486 or placebo.
Study Population:
Key inclusion criteria

Participant must be ≥ 55 years of age inclusive at the time of signing the informed consent

Newly diagnosed, histologically confirmed de novo AML or AML secondary to prior MDS or 
CMML.

Should have undergone induction therapy with intensive chemotherapy with or without 
consolidation therapy as recommended in appropriate guideline(s) or equivalent regimen 
according to institutional standard: having achieved first CR/CRi status within 4 months (± 7 
days) prior to randomization.
Key exclusion criteria

Suspected or proven acute promyelocytic leukemia (FAB M3); or AML with previous 
hematologic disorder such as chronic myeloid leukemia or myeloproliferative neoplasms, 
excluding MDS and CMML.

AML associated with inv(16), t(8;21), t(16;16), t(15;17), or t(9;22) karyotypes or molecular 
evidence of such translocations.

Prior bone marrow or stem cell transplantation.

Candidate for allogeneic bone marrow or stem cell transplant at screening.

Have achieved CR/CRi following therapy with hypomethylating agents

Received therapy with hypomethylating agents for MDS and went on to develop AML within 
four months of discontinuing the therapy with hypomethylating agents.
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Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Intervention Groups and Duration:
Total duration of study participation for each participant: screening phase for 4 weeks, treatment 
phase until AML relapse, and follow-up phase until death, withdrawal of consent, study 
termination, or loss to follow-up.
Dose regimen: 200 mg once daily of CC-486 or placebo will be taken for the first 14 days of each 
28-day treatment cycle.
Dose modification for toxicity and dose/schedule adjustment with AML relapse are allowed.
Study Intervention:
Study Intervention for CA055005
Medication 
Potency 
IP/Non-IP/AxMP
CC-486
150mg/200mg
IP
Placebo
150mg/200mg
IP
Abbreviations: AxMP, auxiliary medicinal product; IP, Investigational Product.
Statistical Methods:
The primary efficacy analysis will be conducted for the Intent-to-Treat Population and will 
compare the RFS distributions between the two treatment groups. A Cox proportional hazards 
model will be used to estimate the corresponding hazard ratio and 95% CI for CC-486 relative to 
placebo. The RFS curves will be estimated using Kaplan-Meier methods.  
Data Monitoring Committee: No
A Data Monitoring Committee or other review committee will not be used in the study.
Other Committee: No
Other review committee will not be used in the study.
Brief Summary:
CA055-005 is designed as a 2:1 randomization of CC-486 or placebo to assess the efficacy and 
safety of maintenance treatment with oral azacitidine in a cohort of Japanese participants ≥ 55 
years with AML, and in CR/CRi after intensive induction chemotherapy with or without 
consolidation chemotherapy. The primary endpoint of RFS and the secondary endpoints of OS, 
safety, PK, and HRQoL will be evaluated and allow for a comprehensive investigation of efficacy, 
exposure/safety, and appropriateness of the clinical recommended dose for the Japanese 
population in comparison with the data from Study CC-486-AML-001.
Study Duration: 3 years
Study Intervention Duration: Until AML relapse in each participant.
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Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Study Visit Frequency: On Days 1, 8, 15 and 22 in Cycles 1 and 2, Days 1 and 15 in Cycles 3
through 24, and Day 1 in Cycle 25 and beyond.
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CA055005
BMS-986345
Oral Azacitidine
2
SCHEDULE OF ACTIVITIES
Study assessments and procedures are presented in Table 2-1 (Screening Procedural Outline), 
Table 2-2 (On Treatment Procedural Outline), and Table 2-3 (Follow-up Procedural Outline).
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BMS-986345
Oral Azacitidine
Table 2-1:
Screening Procedural Outline (CA055005)
Procedure
Screening
(Day -28 to -1)a
Randomiza
tion
(Day -3 to 
Day 1)
Notes
Eligibility Assessments
Informed Consent
X
A participant is considered enrolled only when a protocol-specific informed 
consent is signed. Must be obtained prior to performing any screening procedures. 
Inclusion/Exclusion Criteria
X
Demographics and Medical History
X
All medical history relevant to disease under study
AML Diagnosis History
X
Documentation of AML diagnosis will be assessed locally from bone marrow 
aspirate and/or biopsy sample slides
Transplant Eligibility
X
Including reasons ineligible for transplant
Documentation of Induction ± 
Consolidation Therapies
X
Including cytogenetic risk category information at time of induction therapy
CR/CRi Status Confirmation
X
Safety Assessments
Physical Examination
X
Includes height and weight.
Vital Signs
X
Includes body temperature, blood pressure, heart rate, and respiratory rate.
ECOG Performance Status
X
X
See Appendix 5. Can be performed at randomization or Cycle 1 Day 1.
Prior Medications
X
Includes any prior chemotherapy, cytotoxic therapy, radiation therapy, and all 
medications used for the 4-week period prior to Cycle 1 Day 1.
12-Lead ECG
X
Electrocardiogram required during screening period and whenever clinically 
indicated. This is collected locally. For participants with an abnormal ECG, a 
cardiac consultation should be obtained as deemed necessary by the treating 
physician.
Chest X-ray
X
Chest x-ray not needed if a previous chest x-ray taken within 4 weeks prior to 
Cycle 1 Day 1 is available and not clinically significant. Chest x-ray is collected 
locally.
Protocol Amendment No.: 02
Date: 27-Jun-2023
16
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-1:
Screening Procedural Outline (CA055005)
Procedure
Screening
(Day -28 to -1)a
Randomiza
tion
(Day -3 to 
Day 1)
Notes
Adverse Event Reporting
Monitor for Serious Adverse Events 
X
All SAEs must be collected from the date of participant’s written consent until 28
days post discontinuation of dosing or participant’s participation in the study if the 
last scheduled visit occurs at a later time.
Monitor for Non-Serious Adverse 
Events
X
All non-serious AEs must be collected from the date of participant’s written 
consent until 28 days post discontinuation of dosing or participant’s participation 
in the study if the last scheduled visit occurs at a later time.
Laboratory Tests
See Section 9.4.4
Hematology
X
Includes a complete blood count (RBC count, hemoglobin, hematocrit, mean 
corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean 
corpuscular hemoglobin concentration [MCHC], WBC count with differential, 
ANC, and platelet count).  Any or all laboratory assessments may be repeated 
more frequently if clinically indicated.  The samples will be collected prior to 
study treatment dosing and will be analyzed by the central laboratory.  In the 
event that hematology laboratory results are needed to acutely manage the 
participant, local laboratory tests may be used.  In addition to the local laboratory 
sample, a second sample should always be sent to the central laboratory.
Unstained Peripheral Blood Smear
X
Whenever a hematology sample is collected for a complete blood count, unstained 
peripheral blood smears should be prepared and sent to the central laboratory.  
This unstained peripheral blood smear will be used to assess a manual blood count 
differential.
Serum Chemistry
X
Includes serum chemistry laboratory tests (sodium, potassium, magnesium, 
chloride, bicarbonate, calcium, phosphorus, BUN, creatinine, glucose, albumin, 
total protein, alkaline phosphatase, direct/indirect total bilirubin, aspartate 
aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase 
[LDH], and uric acid).  The samples will be collected prior to study treatment 
dosing and will be analyzed by the central laboratory.  Any or all laboratory 
assessments may be repeated more frequently if clinically indicated.  In the event 
that chemistry laboratory results are needed to acutely manage the participant, 
Protocol Amendment No.: 02
Date: 27-Jun-2023
17
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-1:
Screening Procedural Outline (CA055005)
Procedure
Screening
(Day -28 to -1)a
Randomiza
tion
(Day -3 to 
Day 1)
Notes
local laboratory tests may be used.  In addition to the local laboratory sample, a 
second sample should be sent to the central laboratory.
Coagulation
X
Coagulation testing is conducted at screening and whenever clinically indicated
during the treatment phase.
Urinalysis
X
A standard urinalysis (including microscopic analysis if indicated) is required at 
screening and whenever clinically indicated during the treatment phase.
Pregnancy Test (WOCBP only)
X
A medically supervised serum pregnancy test with sensitivity of at least 25
mIU/mL is to be obtained in female participants of childbearing potential at 
Screening (within 24 hours prior to starting study therapy). 
Viral Serology
X
HBsAg, hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-
HBc), hepatitis C antibody, HIV antibody and if applicable HBV viral DNA and 
HCV viral RNA testing by PCR. For participants with HBV carrier or history of 
HBV infection (HBsAg negative and anti-HBs positive and/or anti-HBc positive), 
signs and symptoms of HBV reactivation should be continuously monitored 
during treatment with appropriate measures including liver function test and HBV 
marker as per the “Guidelines for Handling Hepatitis B Associated with 
Immunosuppression/Chemotherapy”.1
Biomarker Assessments
See Table 9.7-1 for sampling schedule.
Biomarker Blood and Bone Marrow 
Sampling 
X
Blood and bone marrow samples for biomarker assessment are mandatory and 
participant must consent to the collection of these samples.
Pharmacogenomic Blood Sampling
X
Peripheral blood sampling for pharmacogenomic analysis is mandatory and 
participant must consent to the collection of these samples.  Samples should be 
collected when bone marrow is collected at protocol specified time points and 
must be collected on the same day as the bone marrow aspirate procedure.
Efficacy Assessments
Bone Marrow Aspirate
X
A bone marrow aspirate or biopsy (if adequate aspirate is not attainable) should 
ideally be collected at screening, no earlier than 14 days prior to Cycle 1 Day 1.  
The screening bone marrow aspirate and biopsy are required to be repeated even if 
Protocol Amendment No.: 02
Date: 27-Jun-2023
18
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-1:
Screening Procedural Outline (CA055005)
Procedure
Screening
(Day -28 to -1)a
Randomiza
tion
(Day -3 to 
Day 1)
Notes
a bone marrow aspirate and biopsy were performed for disease diagnosis/status as 
part of the standard of care within 28 days of Cycle 1 Day 1.  The bone marrow 
aspirate slide, bone marrow biopsy slide, bone marrow aspirate sample for 
cytogenetics testing/chromosome analysis, and unstained peripheral blood smear 
slides must be sent to the central laboratory for review by the central pathology 
reviewer.
Bone Marrow Biopsy
X
Bone marrow biopsies may be needed to assess bone marrow status.
Cytogenetic Testing
X
Bone marrow aspirate sample tube for cytogenetic testing/chromosome analysis to 
be obtained at Screening for evaluation by the central laboratory to obtain 
karyotype.  A minimum of 16 analyzable metaphases for standard banding 
cytogenetic analysis is recommended at Screening. 
Peripheral Blood Smear
X
Whenever bone marrow aspirate (or biopsy) slides are sent to the central reviewer, 
an unstained peripheral blood smear slide should also be submitted.
Study Intervention
Randomization
X
Randomization should occur within 3 days of Cycle 1 Day 1.
Abbreviations: ALT, alanine aminotransferase; AML, acute myeloid leukemia; ANC, absolute neutrophil count; AST, aspartate aminotransferase; BUN, blood 
urea nitrogen; CR, complete remission; CRi, complete remission with incomplete blood count recovery; DNA, deoxyribonucleic acid; ECG, electrocardiogram; 
ECOG, Eastern Cooperative Oncology Group; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency 
virus; IgG, immunoglobulin G; IgM, immunoglobulin M; LDH, lactate dehydrogenase; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular
hemoglobin concentration; MCV, mean corpuscular volume; RBC, red blood cell; RNA, ribonucleic acid; PCR, polymerase chain reaction; SAE, serious adverse 
reaction; WBC, white blood cell; WOCBP, women of childbearing potential.
a Results obtained on Cycle 1 Day 1 just prior to the first dose will serve as the Baseline values.  If not available, the most recent screening results prior to Cycle 
1 Day 1 will be considered the Baseline values.  Participants who fail eligibility criteria due to low neutrophil count or platelet count or other laboratory 
abnormality can be re-screened as long as this occurs within 4 months (± 7 days) from the achievement of CR or CRi status.
Protocol Amendment No.: 02
Date: 27-Jun-2023
19
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-2:
On-treatment Procedural Outline (CA055005)
Procedure
During 
Treatment
Cycle 1
Day1
(1 Cycle = 
4 Weeks)
During 
Treatment
Cycle 1 
Days 8, 15, 
and 22
(± 3 Days)
During 
Treatment
Cycle 2
Day 1
(± 3 Days)
During 
Treatment
Cycle 2
Days 8, 15, 
and 22
(± 3 days)
During 
Treatment
Cycle 3 and 
beyond
Day 1
(± 3 Days)
During 
Treatment
Cycle 3 and 
beyond
Day 15a
(± 3 Days)
Notes
Safety Assessments
Physical Examination
X
X
X
Includes weight.
ECOG Performance Status
X
X
X
Vital Signs
X
X
X
Includes body temperature, 
blood pressure, heart rate, and 
respiratory rate.
Concomitant Medications, 
Therapy, and Procedures
X
X
X
X
X
X
All concomitant over-the-
counter medications;
prescription medications, 
including anti-infectives for 
prophylaxis and/or treatment of 
an infection; and non-live 
COVID-19 vaccines received
from Cycle 1 Day 1 up to 28 
days after the last dose of IP or 
up to the Treatment 
Discontinuation visit, whichever 
period is longer, must be 
recorded on the appropriate 
page(s) of the CRF.
Protocol Amendment No.: 02
Date: 27-Jun-2023
20
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-2:
On-treatment Procedural Outline (CA055005)
Procedure
During 
Treatment
Cycle 1
Day1
(1 Cycle = 
4 Weeks)
During 
Treatment
Cycle 1 
Days 8, 15, 
and 22
(± 3 Days)
During 
Treatment
Cycle 2
Day 1
(± 3 Days)
During 
Treatment
Cycle 2
Days 8, 15, 
and 22
(± 3 days)
During 
Treatment
Cycle 3 and 
beyond
Day 1
(± 3 Days)
During 
Treatment
Cycle 3 and 
beyond
Day 15a
(± 3 Days)
Notes
Adverse Event Reporting
Monitor for Serious 
Adverse Events
X
X
X
X
X
X
All SAEs must be collected 
from the date of participant’s 
written consent until 28 days 
post discontinuation of dosing 
or participant’s participation in 
the study if the last scheduled 
visit occurs at a later time. 
Monitor for Non-Serious 
Adverse Events
X
X
X
X
X
X
All non-serious AEs must be 
collected from the date of 
participant’s written consent 
until 28 days post 
discontinuation of dosing or 
participant’s participation in the 
study if the last scheduled visit 
occurs at a later time.
Laboratory Tests
See Section 9.4.4.
Hematology
X
X
X
X
X
X
Includes a complete blood count 
(RBC count, hemoglobin, 
hematocrit, mean corpuscular 
volume [MCV], mean 
corpuscular hemoglobin [MCH], 
mean corpuscular hemoglobin 
concentration [MCHC], WBC 
count with differential, ANC, 
and platelet count).  Any or all 
Protocol Amendment No.: 02
Date: 27-Jun-2023
21
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-2:
On-treatment Procedural Outline (CA055005)
Procedure
During 
Treatment
Cycle 1
Day1
(1 Cycle = 
4 Weeks)
During 
Treatment
Cycle 1 
Days 8, 15, 
and 22
(± 3 Days)
During 
Treatment
Cycle 2
Day 1
(± 3 Days)
During 
Treatment
Cycle 2
Days 8, 15, 
and 22
(± 3 days)
During 
Treatment
Cycle 3 and 
beyond
Day 1
(± 3 Days)
During 
Treatment
Cycle 3 and 
beyond
Day 15a
(± 3 Days)
Notes
laboratory assessments may be 
repeated more frequently if 
clinically indicated.  The 
samples will be collected prior 
to study treatment dosing and 
will be analyzed by the central 
laboratory.  In the event that 
hematology laboratory test 
results are needed to acutely 
manage the participant, local 
laboratory tests may be used.  In 
addition to the local laboratory 
sample, a second sample should 
always be sent to the central 
laboratory.
Unstained Peripheral 
Blood Smear
X
X
X
X
X
X
Whenever a hematology sample 
is collected for a complete blood 
count, an unstained peripheral 
blood smear should be prepared 
and sent to the central 
laboratory.  This unstained 
peripheral blood smear will be 
used to assess a manual blood 
count differential.
Serum Chemistry
X
X
X
Includes serum chemistry 
laboratory tests (sodium, 
Protocol Amendment No.: 02
Date: 27-Jun-2023
22
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-2:
On-treatment Procedural Outline (CA055005)
Procedure
During 
Treatment
Cycle 1
Day1
(1 Cycle = 
4 Weeks)
During 
Treatment
Cycle 1 
Days 8, 15, 
and 22
(± 3 Days)
During 
Treatment
Cycle 2
Day 1
(± 3 Days)
During 
Treatment
Cycle 2
Days 8, 15, 
and 22
(± 3 days)
During 
Treatment
Cycle 3 and 
beyond
Day 1
(± 3 Days)
During 
Treatment
Cycle 3 and 
beyond
Day 15a
(± 3 Days)
Notes
potassium, magnesium, 
chloride, bicarbonate, calcium, 
phosphorus, BUN, creatinine, 
glucose, albumin, total protein, 
alkaline phosphatase, 
direct/indirect total bilirubin, 
aspartate aminotransferase 
[AST], alanine aminotransferase 
[ALT], lactate dehydrogenase
[LDH], and uric acid).  The 
samples will be collected prior 
to study treatment dosing and 
will be analyzed by the central 
laboratory.  Any or all 
laboratory assessments may be 
repeated more frequently if 
clinically indicated.  In the event 
that chemistry laboratory test
results are needed to acutely 
manage the participant, local 
laboratory tests may be used.  In 
addition to the local laboratory 
sample, a second sample should 
be sent to the central laboratory.
Protocol Amendment No.: 02
Date: 27-Jun-2023
23
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-2:
On-treatment Procedural Outline (CA055005)
Procedure
During 
Treatment
Cycle 1
Day1
(1 Cycle = 
4 Weeks)
During 
Treatment
Cycle 1 
Days 8, 15, 
and 22
(± 3 Days)
During 
Treatment
Cycle 2
Day 1
(± 3 Days)
During 
Treatment
Cycle 2
Days 8, 15, 
and 22
(± 3 days)
During 
Treatment
Cycle 3 and 
beyond
Day 1
(± 3 Days)
During 
Treatment
Cycle 3 and 
beyond
Day 15a
(± 3 Days)
Notes
Pregnancy Test (WOCBP 
only)
X
X
X
A serum or urine pregnancy test 
(per Investigator’s discretion) is 
to be done prior to Day 1 of 
every subsequent cycle (within 
72 hours). 
If a urine test cannot be 
confirmed as negative (eg, an 
ambiguous result), a serum 
pregnancy test is required. In 
such cases, the participant must 
be excluded from study
participation if the serum 
pregnancy result is positive.
Pharmacokinetic
Assessments
Pharmacokinetics
X
X
X
X
Refer to pharmacokinetics 
collection table in Section 9.5
for timing of collections
Biomarker Assessments
Biomarker Blood and 
Bone Marrow Sampling 
(from the same sample 
taken for central review; 
additional consent 
required)
See Section 9.7
Refer to biomarker collection 
table in Section 9.7 for timing of 
collections.
Blood and bone marrow samples 
for biomarker assessment are 
mandatory and participant must 
consent to the collection of these 
samples.  Samples should be 
Protocol Amendment No.: 02
Date: 27-Jun-2023
24
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-2:
On-treatment Procedural Outline (CA055005)
Procedure
During 
Treatment
Cycle 1
Day1
(1 Cycle = 
4 Weeks)
During 
Treatment
Cycle 1 
Days 8, 15, 
and 22
(± 3 Days)
During 
Treatment
Cycle 2
Day 1
(± 3 Days)
During 
Treatment
Cycle 2
Days 8, 15, 
and 22
(± 3 days)
During 
Treatment
Cycle 3 and 
beyond
Day 1
(± 3 Days)
During 
Treatment
Cycle 3 and 
beyond
Day 15a
(± 3 Days)
Notes
collected when bone marrow is 
collected at protocol specified 
time points and when bone 
marrow is collected to confirm a 
response (CR or CRi) or relapse.
Pharmacogenomic Blood 
Sampling
See Section 9.7
Peripheral blood sampling for 
pharmacogenomic analysis is 
mandatory and participant must 
consent to the collection of these 
samples.  Samples should be 
collected when bone marrow is 
collected at protocol specified 
time points and must be 
collected on the same day as the 
bone marrow aspirate procedure.
Efficacy Assessments
Bone Marrow Aspirate
X
Bone marrow aspirate must be 
collected on Day 1 (± 7 days) of 
Cycles 3, 6, 9, 12, 15, 18, 21, 
24, 30, and 36, to confirm 
continued CR or CRi, relapse 
after CR or CRi (as assessed by 
the Investigator based on CBC 
with WBC differential results), 
or disease relapse.  After Cycle 
36, bone marrow assessment for 
disease relapse will be
Protocol Amendment No.: 02
Date: 27-Jun-2023
25
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-2:
On-treatment Procedural Outline (CA055005)
Procedure
During 
Treatment
Cycle 1
Day1
(1 Cycle = 
4 Weeks)
During 
Treatment
Cycle 1 
Days 8, 15, 
and 22
(± 3 Days)
During 
Treatment
Cycle 2
Day 1
(± 3 Days)
During 
Treatment
Cycle 2
Days 8, 15, 
and 22
(± 3 days)
During 
Treatment
Cycle 3 and 
beyond
Day 1
(± 3 Days)
During 
Treatment
Cycle 3 and 
beyond
Day 15a
(± 3 Days)
Notes
performed only if clinically 
indicated.  
Bone Marrow Biopsy
X
Bone marrow biopsy may be 
needed to assess bone marrow 
status if an adequate bone 
marrow aspirate cannot be 
attained.
Cytogenetic Testing
X
Bone marrow aspirate sample 
tube for cytogenetic
testing/chromosome analysis to 
be obtained for evaluation by 
central laboratory to obtain 
karyotype. During the study, 
repeat of bone marrow 
cytogenetic testing is to be 
completed whenever a bone 
marrow aspirate is obtained.
Peripheral Blood Smear
X
Whenever bone marrow aspirate 
(or biopsy) slides are sent to the 
central reviewer, a peripheral 
blood smear slide should also be 
submitted.
IWG Response 
Assessment
X
International Working Group 
(IWG) response assessment will 
be done at Cycles 3, 6, 9, 12, 15, 
18, 21, 24, 30, and 36.  After 
Cycle 36, response assessment 
for disease relapse will be
Protocol Amendment No.: 02
Date: 27-Jun-2023
26
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-2:
On-treatment Procedural Outline (CA055005)
Procedure
During 
Treatment
Cycle 1
Day1
(1 Cycle = 
4 Weeks)
During 
Treatment
Cycle 1 
Days 8, 15, 
and 22
(± 3 Days)
During 
Treatment
Cycle 2
Day 1
(± 3 Days)
During 
Treatment
Cycle 2
Days 8, 15, 
and 22
(± 3 days)
During 
Treatment
Cycle 3 and 
beyond
Day 1
(± 3 Days)
During 
Treatment
Cycle 3 and 
beyond
Day 15a
(± 3 Days)
Notes
performed only if clinically 
indicated. Participants should be 
assessed for CR/CRi status 
maintenance, relapse after 
CR/CRi, or disease relapse.
Health Outcomes 
Assessments
FACIT-Fatigue Scale and 
EQ-5D-5L
X
X
X
Each assessment should be 
completed at the start of the 
clinic visit prior to dosing and 
other study assessments. See 
Section 9.1.2.
Study Intervention
Dispense/Administer
X
X
X
IP is scheduled to be taken for 
1-14 days of each cycle, unless 
there has been a schedule 
modification from 14 days to 7 
days of IP administration due to 
toxicity. Participants with ≥5% 
to ≤15% blasts in the bone 
marrow or peripheral blood 
response assessment may 
receive 200mg of IP for the first 
21 days per cycle.
Provide/Collect 
Medication Diary
X
X
X
Protocol Amendment No.: 02
Date: 27-Jun-2023
27
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Abbreviations: ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CBC, complete blood 
count; COVID-19, coronavirus disease 2019; CR, complete remission; CRF, case report form; CRi, complete remission with incomplete blood count recovery; 
ECOG, Eastern Cooperative Oncology Group; EOT, end of treatment; EQ-5D-5L, EuroQol 5-dimension 5-level questionnaire; FACIT, Functional Assessment of 
Chronic Illness Therapy; IgG, immunoglobulin G; IgM, immunoglobulin M; IP, Investigational Product; IWG, International Working Group; LDH, lactate 
dehydrogenase; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; RBC, red blood 
cell; SAE, serious adverse event; WBC, white blood cell; WOCBP, women of childbearing potential.
a Beginning with the Cycle 25 Day 15 visit, assessments are optional and will occur only if clinically indicated at the discretion of the Investigator.
Protocol Amendment No.: 02
Date: 27-Jun-2023
28
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-3:
End-of-treatment and Follow-up Procedural Outline (CA055005)
Procedure
End of 
Treatment
/Early 
Termination
Follow-up
Notes
Safety Assessments
Physical Examination
X
Includes weight.
Vital Signs
X
Includes body temperature, blood pressure, heart rate, and respiratory rate.
Concomitant Medications, Therapy, 
and Procedures
X
X
All concomitant over-the-counter medications; prescription medications, including 
anti-infectives for prophylaxis and/or treatment of an infection; and non-live 
COVID-19 vaccines received from Cycle 1 Day 1 up to 28 days after the last dose 
of IP or up to the Treatment Discontinuation visit, whichever period is longer, must 
be recorded on the appropriate page(s) of the CRF.
Monitor for Serious Adverse Events 
Assessment
X
X
All SAEs must be collected from the date of participant’s written consent until 28
days post discontinuation of dosing or participant’s participation in the study if the 
last scheduled visit occurs at a later time. 
Monitor for Non-Serious Adverse 
Events
X
X
All non-serious AEs must be collected from the date of participant’s written 
consent until 28 days post discontinuation of dosing or participant’s participation in 
the study if the last scheduled visit occurs at a later time.
Laboratory Tests
See Section 9.4.4.
Hematology
X
Includes a complete blood count (RBC count, hemoglobin, hematocrit, mean 
corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean 
corpuscular hemoglobin concentration [MCHC], WBC count with differential, 
ANC, and platelet count).  Any or all laboratory assessments may be repeated more 
frequently if clinically indicated.  The samples will be collected prior to study 
treatment dosing and will be analyzed by the central laboratory.  In the event that 
hematology laboratory results are needed to acutely manage the participant, local 
laboratory tests may be used.  In addition to the local laboratory sample, a second 
sample should always be sent to the central laboratory.
Unstained Peripheral Blood Smear
X
Whenever a hematology sample is collected for a complete blood count, unstained 
peripheral blood smears should be prepared and sent to the central laboratory.  This 
Protocol Amendment No.: 02
Date: 27-Jun-2023
29
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-3:
End-of-treatment and Follow-up Procedural Outline (CA055005)
Procedure
End of 
Treatment
/Early 
Termination
Follow-up
Notes
unstained peripheral blood smear will be used to assess a manual blood count 
differential.
Serum Chemistry
X
Includes serum chemistry laboratory tests (sodium, potassium, magnesium, 
chloride, bicarbonate, calcium, phosphorus, BUN, creatinine, glucose, albumin, 
total protein, alkaline phosphatase, direct/indirect total bilirubin, aspartate 
aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase 
[LDH], and uric acid).  The samples will be collected prior to study treatment 
dosing and will be analyzed by the central laboratory.  Any or all laboratory 
assessments may be repeated more frequently if clinically indicated.  In the event 
that chemistry laboratory test results are needed to acutely manage the participant, 
local laboratory tests may be used.  In addition to the local laboratory sample, a 
second sample should be sent to the central laboratory.
Pregnancy Test (WOCBP only)
X
A serum or urine pregnancy test (per Investigator’s discretion) is to be done at the 
EOT visit.
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum 
pregnancy test is required. In such cases, the participant must be excluded from 
study participation if the serum pregnancy result is positive.
Biomarker Assessments
Biomarker Blood and Bone Marrow 
Sampling (from the same sample taken 
for central review; additional consent 
required)
X
Refer to biomarker collection table in Section 9.7 for timing of collections.
Blood and bone marrow samples for biomarker assessment are mandatory and 
participant must consent to the collection of these samples.  Samples should be 
collected when bone marrow is collected at protocol specified time points and when 
bone marrow is collected to confirm a response (CR or CRi) or relapse.  
Pharmacogenomic Blood Sampling
X
Peripheral blood sampling for pharmacogenomic analysis is mandatory and 
participant must consent to the collection of these samples.  Samples should be 
collected when bone marrow is collected at protocol specified time points and must 
be collected on the same day as the bone marrow aspirate procedure.
Protocol Amendment No.: 02
Date: 27-Jun-2023
30
3.0
Approved
930174816
3.0
v
Approved
1.0
v

Clinical Protocol
CA055005
BMS-986345
Oral Azacitidine
Table 2-3:
End-of-treatment and Follow-up Procedural Outline (CA055005)
Procedure
End of 
Treatment
/Early 
Termination
Follow-up
Notes
Efficacy Assessments
Bone Marrow Aspirate
X
If disease relapse features are observed following a bone marrow aspirate, it is
recommended that a repeat bone marrow aspirate be performed at least 3 to 4 weeks 
later to confirm disease relapse unless the blast count was > 50% in the marrow or
peripheral blood.
Bone Marrow Biopsy
X
Bone marrow biopsy may be needed to assess bone marrow status if an adequate 
bone marrow aspirate cannot be attained.
Cytogenetic Testing
X
Bone marrow aspirate sample tube for cytogenetic testing/chromosome analysis to 
be obtained for evaluation by central laboratory to obtain karyotype.
Peripheral Blood Smear
X
Whenever bone marrow aspirate (or biopsy) slides are sent to the central reviewer, 
a peripheral blood smear slide should also be submitted.
IWG Response Assessment
X
Participants should be assessed for CR/CRi status maintenance, relapse after 
CR/CRi, or disease relapse.
Follow-up AML Relapse
X
All discontinued participants, regardless of reason for discontinuation, should be 
followed for AML relapse every 4 weeks (± 3 days) for the first year and then 
every 12 weeks (± 14 days) until death, loss to follow-up, withdrawal of consent 
from further follow-up, or end of study.  Documentation such as laboratory or 
pathology reports, bone marrow reports, and/or peripheral blood reports supporting 
the AML relapse should be requested and collected.
Follow-up AML Therapies
X
All discontinued participants, regardless of reason for discontinuation, should be 
followed for AML therapies every 4 weeks (± 3 days) for the first year and then 
every 12 weeks (± 14 days) until death, loss to follow-up, withdrawal of consent 
from further follow-up, or end of study.
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Table 2-3:
End-of-treatment and Follow-up Procedural Outline (CA055005)
Procedure
End of 
Treatment
/Early 
Termination
Follow-up
Notes
Survival Follow-up
X
All discontinued participants, regardless of reason for discontinuation, should be 
followed for survival every 4 weeks (± 3 days) for the first year and then every 12 
weeks (± 14 days) until death, lost to follow-up, withdrawal of consent from further 
follow-up, or the end of the study.  The survival follow-up can be performed via a 
telephone interview.
Health Outcomes Assessments
FACIT-Fatigue Scale and EQ-5D-5L 
X
Each assessment should be completed at the start of the clinic visit prior to dosing 
and other study assessments. See Section 9.1.2.
Abbreviations: ALT, alanine aminotransferase; AML, acute myeloid leukemia; ANC, absolute neutrophil count; AST, aspartate aminotransferase; BUN, blood 
urea nitrogen; COVID-19, coronavirus disease 2019; CR, complete remission; CRF, case report form; CRi, complete remission with incomplete blood count 
recovery; EOT, end of treatment; EQ-5D-5L, EuroQol 5-dimension 5-level questionnaire; FACIT, Functional Assessment of Chronic Illness Therapy; IgG, 
immunoglobulin G; IgM, immunoglobulin M; IP, Investigational Product; IWG, International Working Group; LDH, lactate dehydrogenase; MCH, mean 
corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; RBC, red blood cell; SAE, serious adverse event; 
WBC, white blood cell; WOCBP, women of childbearing potential.
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3
INTRODUCTION
This is a Phase 2, randomized, double-blind, placebo-controlled study to compare the efficacy and 
safety of CC-486 plus best supportive care versus best supportive care as maintenance therapy in 
Japanese participants with acute myeloid leukemia (AML) in complete remission. The primary 
objective of the study is to evaluate whether maintenance therapy with CC-486 improves relapse-
free survival (RFS) compared with placebo in Japanese participants ≥ 55 years with AML, who 
have achieved first complete remission (CR) or complete remission with incomplete blood count 
recovery (CRi) after induction with intensive chemotherapy with or without consolidation 
chemotherapy. Participants will be randomized 2:1 to receive 200 mg CC-486 once daily (QD) or 
placebo for the first 14 days of each 28-day treatment cycle.
A detailed description of the chemistry, pharmacology, efficacy, and safety of CC-486 is provided 
in the Investigator’s Brochure (IB).
3.1
Study Rationale
The standard treatment modality for acute myeloid leukemia (AML) is chemotherapy globally as 
well as in Japan. The therapeutic approaches are usually divided into two phases: induction of 
remission and post-remission (consolidation) therapy. A common induction regimen consists of 
cytarabine 100 mg/m2/day for 7 days combined with daunorubicin 60 to 90 mg/m2/day for 3 
days, often referred to as the “7+3 protocol.” For post-remission chemotherapy, the same 
chemotherapy agent used for remission induction is often repeated for one or more cycles, 
referred to as consolidation chemotherapy. When several courses of consolidation are given, 
despite achieving complete remission (CR), approximately 50% of younger (< 60 years) and 
80% to 90% of older (≥ 65 years) patients will relapse; most of these patients will die due to 
AML, with median survival from 3 to 12 months after relapse. For patients with relapsed AML, 
the duration of first CR is strongly correlated with subsequent outcomes, with longer duration of 
first CR associated with better survival. Therefore, an unmet medical need exists for maintaining 
a deeper level of remission over a longer duration in patients who achieve remission. Effective 
maintenance therapy for patients who attain remission with intensive chemotherapy may play a 
role in preventing relapse and prolonging overall survival (OS), especially in those ineligible for 
allogeneic hematopoietic stem cell transplantation (HSCT).
CC-486 was confirmed to show statistically significant prolongation of OS and relapse-free 
survival (RFS) in the maintenance setting in patients ≥ 55 years with AML and in CR or complete 
remission with incomplete blood count recovery (CRi) after conventional induction chemotherapy 
with or without consolidation chemotherapy in Study CC-486-AML-001.  CC-486 was already 
approved for the treatment of AML in the United States (US) in September 2020, in Canada in 
January 2021, and the European Union in June 2021. CC-486 is recommended for as maintenance 
therapy for patients with AML in complete remission, regardless of age (<60 or ≥ 60 years), in the 
National Comprehensive Cancer Network (NCCN) Clinical Practice Guideline (Category 2B).2
CA055-005 is a bridging study to provide clinical data that will allow extrapolation of the CC-
486-AML-001 study data to Japan. This study is designed as a 2:1 randomization of CC-486 or 
placebo to assess the efficacy and safety of maintenance treatment with oral azacitidine in a cohort 
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of Japanese participants ≥ 55 years with AML and in CR/CRi after conventional induction 
chemotherapy with or without consolidation chemotherapy. The primary endpoint is RFS because 
CC-486-AML-001 has successfully shown survival benefit for not only OS but RFS when 
compared with best supportive care (BSC). The CC-486 dose that has demonstrated tolerability 
and shown signs of clinical activity in the ORACLE Study is 200 mg. The primary endpoint of
RFS and secondary endpoints of OS, time to relapse from CR/CRi, time to discontinuation from 
treatment, safety, pharmacokinetics (PK), and health-related quality-of-life (HRQoL) will be 
evaluated and allow for a comprehensive investigation of efficacy, exposure/safety, and HRQoL 
appropriateness of the clinical recommended dose for the Japanese population in comparison with 
the data from the Study CC-486-AML-001.
3.2
Background
Acute Myeloid Leukemia
Leukemia is a neoplastic proliferation of hematopoietic cells. These cells are either at 
undifferentiated or partially differentiated stages of maturation.  As a consequence of excessive 
proliferation of the immature precursors, these cells eventually replace the normal blood-forming 
elements of the bone marrow, resulting in neutropenia, anemia, and thrombocytopenia.  Acute 
myeloid leukemia (AML) can occur at any age and accounts for one-third of the leukemias 
diagnosed in patients >20 years.  Incidence increases with age, with the median age at time of 
diagnosis around 68 years and the median age at time of death around 72 years3 4.  In individuals 
≥ 65 years, the incidence of AML is almost 10 times higher than in those < 65 years (17 per 
100,000 versus 1.8 per 100,000, respectively)5. In Japan, the number of AML patients is estimated 
to be about 7,000 in 20176. The incidence of AML in Japan is estimated to be 2 to 3 per 100,000, 
and the incidence increases with age in Japan as in the US.7
Two classification systems have been used for defining AML. In the classic French-American-
British (FAB) system, morphology (based primarily on cytochemistry) defines the level of 
maturation and differentiation of the blasts; the threshold between myelodysplasia and AML is 
arbitrarily drawn at 30% blasts.  Eight subtypes of AML have been described and are named 
according to the involved cell type.  The more recent World Health Organization (WHO)
classification seeks to further refine differences in leukemia biology by incorporating cytogenetic 
information, prior history of myelodysplasia, or therapy with certain chemotherapy agents or
radiation therapy and presence of dysplasia8. 
More recently, the prognostic risk in AML is determined not only by cytogenetic abnormalities, 
(ie, chromosomal deletions, duplications, or translocations) but also by several somatic molecular 
alterations (gene mutations)2. The molecular genetic landscape of AML is complex, and several 
genes like CEBPA, NPM1, FLT3, RUNX1, P53, and ASXL1 are now part of risk assessments of 
AML patients. The current European LeukemiaNet (ELN) favorable risk criteria include 
t(8;21)(q22;q22.1); RUNX1-RUNX1T1; inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-
MYH11. Normal cytogenetics portends intermediate-risk AML.  AML that is often characterized 
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by deletions of the long arms (monosomies) of chromosomes 5 or 7; by translocations or inversions 
of chromosome 3, t(6;9), t(9;22); or by abnormalities of chromosome 11q23 have particularly poor 
prognoses with chemotherapy.  Acute myeloid leukemia may also arise secondary to previous 
cytotoxic chemotherapy or arise through transformation from existing myelodysplasia.  Therapy-
related AML arising from exposure to environmental toxins, cytotoxic drugs, or radiation currently 
accounts for about 10% to 30% of all cases of AML9.  It is estimated that 35% to 40% of patients 
with myelodysplastic syndromes (MDS) will develop AML, with the disease often refractory to 
current therapy10.
Current AML Treatments
The standard treatment modality for AML is chemotherapy globally, including in Japan. The 
therapeutic approaches are usually divided into two phases: induction of remission and post-
remission (consolidation) therapy.  For more than 30 years, the combination of cytarabine and an 
anthracycline has been the mainstay of treatments to induce remission11 12. The induction of 
remission therapy in leukemia is designed to produce rapid restoration of normal bone marrow 
function.  A common induction regimen consists of cytarabine 100 mg/m2/day for 7 days combined 
with daunorubicin 60 to 90 mg/m2/day for 3 days, often referred to as the “7+3 protocol.”  With 
the combination of cytarabine and daunorubicin or their analogues, a CR, conventionally defined 
by the presence of < 5% blasts in the bone marrow together with recovery of peripheral-blood 
absolute neutrophil and platelet counts, can be achieved in up to 60% to 80% of adults with de 
novo AML who are < 60 years11 12. If CR is achieved, there are three basic treatment choices for 
post-remission therapy: additional chemotherapy, stem cell transplantation from a donor 
(allogeneic stem cell transplantation), or stem cell transplantation using the patient's own stem 
cells (autologous stem cell transplantation). For post-remission chemotherapy, the same 
chemotherapy agent used for remission induction is often repeated for one or more cycles, referred 
to as consolidation chemotherapy. When several courses of consolidation are given, survival rates 
at 2 to 3 years are 35% to 50% for young to middle-aged (< 65 years) adults who have achieved 
CR13.  However, consolidation or post-remission chemotherapy for elderly (≥65 years) patients 
with AML has not been proven beneficial.
In elderly patients with AML, conventional cytotoxic intensive chemotherapy has been associated 
with CR rates of approximately 45%, considerably lower than in younger (< 60 years) patients.  
Unfortunately, the duration of remission is shorter, the early treatment-related mortality is high
(approximately 30% to 50%)14, which in part explains a median survival time between 9 to 12 
months15 16. The standard consolidation chemotherapy regimens are not associated with prolonged 
CR in this elderly age group17.
When standard chemotherapy (consolidation after remission induction) is given to patients < 65 
years, the 5-year survival rate is 48%18. The 4-year survival rate is reported to be approximately 
20% for patients aged 65 to 80 years19. In Japan, the basic treatment regimen is the same as the 
above-mentioned treatment regimen outside Japan. For elderly patients, the general conditions and 
the presence/absence of complications are taken into account when deciding whether induction 
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therapy should be indicated and when determining the dose of chemotherapy once induction 
therapy is indicated. If considered to fit the standard treatment, these patients receive induction 
therapy, as do younger patients. If remission is achieved, patients receive allogeneic HSCT if
eligible or consolidation therapy or chemotherapy depending on prognostic factors. If remission 
cannot be achieved, salvage therapy. will be performed20. CC-486 maintenance therapy was added 
as one option (Category 2B) in the NCCN Clinical Practice Guideline based on the result of the 
Study CC-486-AML-00121; however, maintenance therapy has not been established in Japan22, 
and until recently, there is no standard for maintenance therapy. Patients who are not candidates 
for intensive remission induction therapy, such as older adult patients, are treated with low-dose 
cytarabine, injectable azacitidine with venetoclax, or new drugs16 23.
CC-486 (Oral Azacitidine)
Azacitidine is an analog of the naturally occurring pyrimidine nucleoside cytidine and is classified 
as an antimetabolite. Vidaza® (injectable azacitidine) is approved by the US Food and Drug 
Administration (FDA) for the following 5 subtypes of the French-American-British (FAB) 
classification system of MDS: refractory anemia (RA) or refractory anemia with ringed 
sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring 
transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts 
in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMML). Vidaza is also 
approved by the European Commission for the treatment of adult participants who are not eligible 
for HSCT with intermediate-2 and high-risk MDS according to the Revised International 
Prognostic Scoring System (IPSS-R); CMML with 10% to 29% marrow blasts without 
myeloproliferative disorder; AML with 20% to 30% blasts and multi-lineage dysplasia according 
to World Health Organization (WHO) classification; and AML with >30% blasts according to 
WHO classification.
Azacitidine has been extensively studied in MDS and has been shown in a large, randomized Phase 
3 trial of higher-risk MDS participants to provide a survival advantage of 9.4 months over 
conventional care regimens, thus altering the natural course of MDS. The median overall survival 
(OS) of azacitidine-treated participants was 24.5 months compared with 15.0 months for the 
combined conventional care regimen group, which included best supportive care (BSC), low-dose 
cytarabine, and intensive chemotherapy24. Silverman et al25, using WHO AML criteria for 
diagnosis, reported a median OS of 19.3 months (n=27) in azacitidine-treated participants 
compared with 12.9 months (n=25) in participants who received BSC. More recently, a 
multicenter, randomized, Phase 3 study in untreated AML participants reported a CR rate of 27.8%
and a clinically meaningful improvement in OS. The median OS was longer for participants treated 
with azacitidine at 10.4 months compared to those who received conventional care regimens at 6.5 
months26. All of the above-mentioned studies used the standard azacitidine dose of 75 mg/m2/day 
subcutaneous (SC) for 7 days of each 28-day cycle27.
The QUAZAR Study (CC-486-AML-001) has demonstrated that CC-486 maintenance therapy 
was associated with significantly longer overall and relapse-free survival than placebo among 
older patients with AML who were in remission after chemotherapy. CC-486 was approved in the 
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US and Canada in September 2020 and January 2021, respectively, and is indicated for continued 
treatment of adult patients with AML who achieved first CR/CRi following intensive induction 
chemotherapy and are not able to complete intensive curative therapy28. An oral formulation of 
azacitidine (CC-486) has been developed and is currently being evaluated in clinical trials, either 
as a single agent or in combination with other drugs, for the treatment of hematological and solid 
malignancies.  This oral formulation of azacitidine provides an opportunity for administration in a 
more convenient outpatient setting rather than in the hospital/clinic setting. Home administration 
also alleviates the morbidity of injection and catheter-site reactions and avoids the inconvenience 
and resource utilization costs associated with frequent hospital/clinic visits. 
Results from the ongoing Phase 3, randomized, double-blind, placebo-controlled QUAZAR Study 
(CC-486-AML-001), which enrolled de novo AML and secondary AML participants, have shown 
that CC-486 (300 mg/day for 14 days of 28-day treatment cycles) as first-line maintenance therapy 
demonstrated significant and clinically meaningful improvement in OS and relapse-free survival 
(RFS) in AML in remission following induction chemotherapy with or without consolidation.  
Median follow-up was 41.2 months. Median OS was 24.7 months with CC-486 versus 14.8 months 
with placebo (P=0.0009; HR 0.69 [95% CI 0.55, 0.86]). Median RFS was 10.2 months in the CC-
486 arm compared to placebo at 4.8 months (P=0.0001; HR 0.65 [95% CI 0.52, 0.81])29. The RFS 
rate at the 6-month time point was 67.4% in the CC-486 group and 45.2% in the placebo group, 
for a difference of 22.2%. The RFS rates were consistently higher for the CC-486 group than for 
the placebo group at each of the later time points (44.9% versus 27.4% at the 1-year time point 
and 26.6% versus 17.4% at the 2-year time point, respectively).
3.3
Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and reasonably 
anticipated adverse events (AEs) of CC-486 may be found in the Investigator’s Brochure (IB).
3.3.1
Risk Assessment
Table 3.3.1-1:
Risk Assessment
Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s)
Known/potential safety risks
The known side effects associated with 
azacitidine treatment as very common (a 
10% or more chance that this will 
happen) are:
anemia, neutropenia, leukopenia, febrile 
neutropenia, thrombocytopenia, 
bronchitis, cellulitis, pneumonia, oral 
fungal infection, skin infection, 
respiratory tract infection, upper 
respiratory tract infection, urinary tract 
infection, nausea, vomiting, diarrhea, 
Patients should be monitored 
closely and appropriate actions 
taken following recommendations 
in Section 7.4.1.
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Table 3.3.1-1:
Risk Assessment
Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
abdominal pain, upper abdominal pain, 
abdominal discomfort, constipation, 
asthenia, fatigue, malaise, pyrexia, 
nasopharyngitis, pharyngitis, laryngeal 
pain, decreased appetite, weight 
decreased, hypokalemia, arthralgia, back 
pain, bone pain, myalgia, 
musculoskeletal pain, pain in extremity, 
chest pain, dizziness, headache, 
insomnia, dyspnea, dyspnea exertional, 
rash, skin lesion, pruritus, ecchymosis, 
hematoma, petechiae, and epistaxis.
Study Procedures
Study design
Lower dose may not be able to show the 
comparable results with AML-001study
in spite of consistently observed 
equivalent exposure of 200 mg in 
Japanese participants as 300 mg in 
Caucasian participants.
Although the feasible number of 
subjects is limited, subjects are 
enrolled as many as possible. And
evaluate comprehensively that the 
results of not only the primary 
endpoint but also the secondary 
endpoints and safety are at least not 
substantially inconsistent with the 
results of AML-001 study and also 
assess in detail the efficacy and 
safety for individual subjects.
Study design
Small sample size may not be able to 
show the comparable results with AML-
001study.
Although the feasible number of 
subjects is limited, subjects are 
enrolled as many as possible. And
evaluate comprehensively that the 
results of not only the primary 
endpoint but also the secondary 
endpoints and safety are at least not 
substantially inconsistent with the 
results of AML-001 study and also 
assess in detail the efficacy and 
safety for individual subjects.
Study execution
It may take time to enroll the target 
population for the following reasons:

anticipated limited number of patients 
who are fit for intensive 
chemotherapy but not allogeneic SCT 
(such intensive chemotherapy is for 
patients who are usually fit for 
allogeneic SCT as well)

setting a placebo-control arm

Carefully choose the study sites 
with high motivation to join this 
study and have recently shown 
good performance in
hematologic malignancy 
studies.

Disseminate messages of CC-
486-AML-001 study results as 
much as possible to encourage 
investigators and participants 
for this study.
Abbreviations: mRFS, median relapse-free survival; SCT, stem cell transplantation
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3.3.2
Benefit Assessment
Benefit considerations may include:

Prolongation of RFS in the maintenance setting of CC-486 compared with BSC.

Contribution to provide actual evidence in Japanese participants with AML in complete 
remission (ie, whether similar benefit can be expected in Japanese participants).
3.3.3
Overall Benefit/Risk Conclusion
Taking into account the measures taken to minimize risk to participants in this study, the potential 
risks identified in association with CC-486 are justified by the anticipated benefits that may be 
afforded to participants with AML.
The Sponsor will evaluate the risk/benefit profile of the study on an ongoing basis. This evaluation 
will be based on all available data – with particular attention to AEs or other safety trends in this 
or any other clinical study of CC-486 whose character, severity, and/or frequency suggest that 
participants would be exposed to an unreasonable and significant risk of illness or injury.
If such evaluation suggests that the risk/benefit profile of the study has become unfavorable to 
participants, the Sponsor will pause enrollment and/or treatment until further evaluation of data, 
and interaction with the appropriate health authority(ies) can take place on potential actions. Such 
actions may include (but are not limited to) study continuation, substantial amendment, or 
termination of the study.
4
OBJECTIVES AND ENDPOINTS
Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
Estimands
Primary Objective
Primary Endpoint
Primary Estimand

To evaluate the efficacy of 
CC-486 
as 
maintenance 
therapy by using RFS in 
Japanese participants ≥ 55 
years with AML who have 
achieved first CR or CRi
after 
induction 
with 
intensive 
chemotherapy 
with 
or 
without 
consolidation 
chemotherapy.

RFS

Population: All randomized Japanese 
participants ≥ 55 years with AML, who 
have achieved first CR or CRi after 
induction with intensive chemotherapy 
with 
or 
without 
consolidation 
chemotherapy.

Treatment: CC-486 +/- BSC vs placebo 
+/- BSC as randomized

Intercurrent events: Participants without 
documented relapse at the time of study 
closure and participants who are 
withdrawn for any reason or start 
subsequent therapy will be censored.

Summary 
statistics: 
Kaplan-Meier 
curves, and hazard ratios from Cox
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
Estimands
proportional 
hazards 
model 
with 
confidence interval.
Secondary
Secondary
To determine the effect of 
CC-486 
as 
maintenance 
therapy on OS, time to 
relapse from CR/CRi, and 
time to discontinuation from 
treatment
To determine safety and 
tolerability
To determine PK
To determine the effect of 
oral 
azacitidine 
on 
HRQoL
OS
Time 
to 
relapse 
from 
CR/CRi
Time to discontinuation 
from treatment
Safety/tolerability 
(type, 
frequency, severity, and 
relationship of AEs to 
study treatments; physical 
examinations, vital signs; 
clinical 
laboratory 
evaluations, 
and 
concomitant 
medication/therapy)
PK parameters
Participant-reported 
outcomes 
utilizing 
the 
FACIT-Fatigue Scale and 
the EQ-5D-5L

Population: 

OS, time to relapse from CR/CRi, 
time 
to 
discontinuation 
from 
treatment,
and 
HRQoL:
All 
randomized Japanese participants ≥ 
55 years with AML who have 
achieved first CR or CRi after 
induction 
with 
intensive 
chemotherapy with or without 
consolidation chemotherapy.

Safety/tolerability: 
All 
treated 
participants

PK
parameters: All participants 
with PK sampling with CC-486 
treatment

Treatment: 

OS, time to relapse from CR/CRi, 
time 
to 
discontinuation 
from 
treatment, safety/tolerability, and 
HRQoL:
CC-486 +/-
BSC vs 
placebo +/- BSC as randomized

PK parameters: CC-486 +/- BSC

Intercurrent events:

OS: Lost to follow-up or all other 
intercurrent events

Time to relapse from CR/CRi: 
Death or start of subsequent therapy

Time 
to 
discontinuation 
from 
treatment: Relapse, death, or start of 
subsequent therapy

Safety/tolerability, PK parameters 
and HRQoL: All intercurrent events 
(eg, start of subsequent therapy)
will be handled with treatment 
policy (ie, use information after 
intercurrent event)

Summary statistics: 

OS, time to relapse from CR/CRi,
and time to discontinuation from 
treatment: hazard ratio from Cox 
proportional hazards model with 
confidence interval
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
Estimands

Safety/tolerability: Proportion of 
patients with event within treatment 
arms

PK parameters: PK parameters in 
CC-486 arm

HRQoL: Difference of HRQoL 
change from baseline scores within 
treatment arms
Exploratory 
Exploratory
To determine plasma 
concentration of azacitidine 
and explore exposure-
response relationships of 
efficacy and safety 
endpoints

To determine cytogenetic 
status as indicator of 
pending AML relapse
To evaluate molecular 
and/or cellular markers in 
the blood and bone marrow 
post induction and during 
maintenance therapy that 
may be predictive of 
clinical outcomes with oral 
azacitidine, including OS 
and RFS, following CR/CRi

Correlative analyses to 
assess the relationships 
between 
azacitidine 
exposure 
and 
safety,
efficacy, and exploratory 
pharmacodynamic 
endpoints 
(eg, 
DNA 
methylation)

Analysis 
of 
genetic 
alterations, 
including 
gene 
sequencing 
for 
recurrent 
gene 
aberrations in AML

Flow cytometric analysis 
of hematopoietic cell 
immunophenotypes -
MRD
Abbreviations: AE, adverse event; AML, acute myeloid leukemia; BSC, best supportive care; CR, complete remission; 
CRi, complete remission with incomplete blood count recovery; DNA, deoxyribonucleic acid; EQ-5D-5L, EuroQol 
5-dimension 5-level questionnaire; FACIT, Functional Assessment of Chronic Illness Therapy; HRQoL, health-
related quality of life; IgG, immunoglobulin G; MRD, minimal residual disease; OS, overall survival; PK, 
pharmacokinetic(s); RFS, relapse-free survival.
5
STUDY DESIGN
5.1
Overall Design
This is a multicenter, placebo-controlled, Phase 2 study with a double-blind, randomized, 2:1 
group design in Japanese participants with de novo AML or AML secondary to prior diagnosis of 
MDS or CMML, aged ≥ 55 years, who are in first CR/CRi following induction therapy with or 
without consolidation chemotherapy.
The study consists of 3 phases; the Screening Phase, the Treatment Phase, and the Follow-up 
Phase. The study design schematic is presented in Figure 5.1-1.
Approximately 15 participants will be randomized 2:1 to CC-486 or placebo. 
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
Approximately 10 participants will receive CC-486.

Approximately 5 participants will receive placebo.
After informed consent is obtained, participants will undergo screening procedures to determine
eligibility (28 days for screening). Eligible participants will be dynamically randomized using an 
Interactive Response Technology (IRT) by the following factors:
1. Age: 55 to 64 years/ ≥65 years
2. Prior history of MDS/CMML: Yes/No
3. Cytogenetic risk: Intermediate/Poor
4. Consolidation therapy: Yes/No
Randomization must occur within 4 months (± 7 days) of achieving the first CR/CRi.
After randomization, no crossover between the treatment arms will be permitted at any point
during the study.  During the Double-blind Treatment Phase, participants will ingest 
Investigational Product (IP) (CC-486 tablets or placebo tablets) for the first 14 days of each 28-
day cycle.  Dose modifications may occur for managing toxicity if necessary during treatment 
(Section 7.4.1).
During the Double-blind Treatment Phase, participants will be assessed for safety, tolerability, and 
efficacy.  Assessments during the Double-blind Treatment Phase will include monitoring for AEs, 
monitoring for relapse of AML, physical examination, vital signs and weight measurement, 
Eastern Cooperative Oncology Group (ECOG) performance status, hematology and serum 
chemistry, pregnancy testing (women of childbearing potential [WOCBP] only), concomitant 
medications, therapies and procedures, review of bone marrow aspirate (or biopsy if adequate 
aspirate is not attainable) and peripheral blood smear slides, cytogenetic analysis, CR/CRi status 
assessment, bone marrow and peripheral blood sampling for biomarker analysis, blood sampling 
for PK analysis, IP administration and accountability, and HRQoL.
A separate central review of all bone marrow aspirates, bone marrow biopsies, and peripheral 
blood smears will be conducted by a pathologist blinded to participant treatment.  The central 
reviewer’s assessments will be used to confirm the CR/CRi status at screening and during 
treatment for maintenance assessment.  If the central reviewer and local pathologist disagree on 
the CR/CRi status of a participant, a third-party reviewer will adjudicate and make the final 
assessment.  
The central cytogenetic review will provide standardized analysis and reporting for all participants, 
regardless of the laboratory performing the initial analysis (local or central).
In participants on study who have subsequent evidence of AML relapse with blasts ≥5%, either in 
the peripheral blood or bone marrow, and provided the blasts are no greater than 15% in the blood 
or bone marrow, escalation of the dosing regimen (dose and/or schedule) can be implemented
(Section 7.4.2).
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Participants will be discontinued from treatment when they meet the following criteria:

Appearance of > 15% blasts in the bone marrow or peripheral blood.

The above occurrence should be attributed to relapse following CR/CRi and not attributable to 
any other cause (eg, bone marrow regeneration after consolidation therapy).
All discontinued participants, regardless of reason for discontinuation, should undergo Treatment 
Discontinuation Visit procedures at the time of study discontinuation.  Participants will have a 
follow-up visit for the collection of AEs up to 28 days after last dose of IP or up to the Treatment 
Discontinuation Visit, whichever is longer.  After this follow-up visit, participants will be followed 
for survival every month for the first year and then every 3 months until death, withdrawal of 
consent for further follow-up, until a participant is lost to follow-up or study end, or when the 
commercial product of CC-486 becomes available at the site, whichever comes first.
Figure 5.1-1:
Study Design Schema
5.1.1
Data Monitoring Committee and Other Committees
A Data Monitoring Committee or other review committee will not be used in the study.
5.2
Number of Participants
Approximately 15 participants will be randomized 2:1 to receive CC-486 or placebo.
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5.3
End of Study Definition
The start of the trial is defined as the first participant first visit. End of trial is defined as the last 
participant last visit. Study completion is defined as the final date on which data for the primary 
endpoint were or are expected to be collected, if this is not the same.
A participant is considered to have completed the study if he/she has completed the last visit.
5.4
Scientific Rationale for Study Design
This is a multicenter, randomized, double-blind, placebo-controlled, Phase 2 study in Japanese 
participants ≥ 55 years with AML in CR/CRi following intensive induction therapy with or without 
consolidation therapy. Participants will be randomized 2:1 to receive 200 mg CC-486 (QD or 
placebo for the first 14 days of each 28-day treatment cycle. This is a bridging study to provide 
clinical data that will allow extrapolation of the CC-486-AML-001 study data to Japan. 
One of the most important goals of maintenance therapy for AML should be to minimize the risk 
of relapse and sustain complete remission as long as possible. Study CC-486-AML-001 has shown 
survival benefit on not only OS but RFS when compared with BSC, and the subgroup analyses of 
the primary endpoint (OS) and key secondary endpoints (RFS) showed a consistent efficacy 
benefit of CC-486 across various demographic and disease-related subgroups. Thus, in Study 
CA055-005, RFS is set as a primary endpoint and OS as a secondary endpoint.
When designing CA055-005 as a randomized, placebo-controlled study, the data of median RFS 
from both arms of Study CC-486-AML-001 (ie, 10.2 months vs 4.8 months for the CC-486 arm 
and BSC arm, respectively) were primarily referred to for the statistical sample size calculation.
The target population of this study should be same as that of Study CC-486-AML-to secure 
comparability between the 2 studies for the purpose of bridging. As for the target age, although 
most enrolled participants will be elderly (eg, ≥ 60 years or ≥65 years), the same target age is set 
as in Study CC-486-AML-001 (ie, ≥ 55 years) because the survival benefit in Study CC-486-AML-
001 was observed regardless of age group.
The 2:1 randomization to CC-486 or placebo will be performed to adequately secure the number 
of participants in the CC-486 group and to keep the number of participants in the placebo group to 
a minimum. Best supportive care will include but not be limited to red blood cell (RBC) and 
platelet transfusions; use of an erythropoiesis-stimulating agent (ESA); antibiotic, antiviral, and 
antifungal therapy; nutritional support; and granulocyte-colony stimulating factors (G-CSFs) for 
participants experiencing neutropenic infections. Thus the risk of not providing participants with 
appropriate care is minimized while providing the potential benefit of maintaining CR/CRi status. 
The starting dose for participants is 200 mg CC-486 or placebo QD for the first 14 days of each 
28-day treatment cycle.  This CC-486 dose and schedule have demonstrated tolerability and shown 
signs of clinical activity in a prior study the ORACLE study.  Participants should continue to 
receive CC-486 for at least 2 cycles of treatment before being assessed for discontinuation from 
the study due to disease relapse at the early timing of efficacy evaluation.
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5.4.1
Participant Input Into Study Design
Not applicable.
5.5
Justification for Dose
In Study CC-486 AML-001, the dose and schedule of 300 mg CC-486 orally administered QD for 
the first 14 days of every 28-day treatment cycle were selected based on cumulative safety, 
efficacy, tolerability, and biologic data observed in a recently concluded Phase 1/2 study (AZA 
PH US 2007 CL 005)30 31.  
Study AZA PH US 2007 CL 005 was initially designed to determine the maximum tolerated dose 
of CC-486 administered according to different treatment schedules and to evaluate the 
pharmacokinetic behavior of azacitidine administered by both oral and SC routes.  In Part 2 of the 
AZA PH US 2007 CL 005, following administration of a 200-mg or 300-mg dose, areas under the 
curve (AUCs) were measured on Day 1 and on the last day of dosing (ie, Day 14 or Day 21), and 
then the mean AUC (between Day 1 and Day 14 or 21) was calculated.  Finally, the mean 
extrapolated cumulative azacitidine exposure per cycle was calculated by multiplying the mean 
AUC by the number of dosing days in the treatment cycle (ie, 7, 14, or 21). Similar calculations 
were made for the SC route. The results of the study (AZA PH US 2007 CL 005 Clinical Study 
Report) showed that, compared with SC treatment (75 mg/m2 QD × 7 days), CC-486 300 mg QD 
× 14 days and 21 days provides cumulative exposure per cycle of 38% and 57%, respectively.
The 300-mg QD × 14 days regimen in Study CC-486-AML-001 has also been determined to be 
biologically active (maintaining hypomethylation at the end of treatment cycle at the 28th day) 
and was associated with hematological responses in ~31% of participants treated in Study AZA 
PH US 2007 CL 005. This regimen is also generally well tolerated. Furthermore, this schedule 
may allow participants to remain on study for protracted periods. In particular, with the shorter 
schedule of a 14-day QD regimen (vs the 21-day QD regimen studied in the Study AZA PH US 
2007 CL 005), participants may have a better observance to treatment and better long-term 
tolerance to CC-486, particularly because gastrointestinal dysfunction is common in this patient 
population after undergoing induction therapy for AML. As the CC-486-AML-001 is a 
maintenance study and as participants would be in CR/CRi at study entry with intent to suppress 
relapse occurrence and continue on therapy for up to more than years, the appropriate starting dose 
and schedule was deemed to be 300 mg QD x 14 days of every 28-day cycle.
Although a clear reason has not yet been elucidated, it has been demonstrated consistently that 
exposure of CC-486 is different between Japanese and non-Japanese participants. As far as the 
Japanese population is concerned, two Phase 1 studies have been conducted in Japanese 
participants with hematologic malignancy (AZA-MDS-005 and CC-486-MDS-001). In the MDS-
005, conducted in Japanese participants with MDS, all 4 participants who were evaluated for dose-
limiting-toxicity discontinued the study treatment due to serious adverse event (SAE) (severe 
neutropenia/infection) when CC-486 was given as a QD dose of 300 mg for 21 days/28-day cycle. 
The exposure of 300 mg for 21 days for Japanese participants in AZA-MDS-005 was indicated to 
be higher when compared with that for Caucasian participants.  Study CC-486-MDS-001 was 
accordingly planned to start with a lower dose cohort (ie, 100 mg for 14 days/28 day-cycle). This 
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study was terminated due to the unexpectedly lower enrollment in this lower dose cohort, but it 
was again indicated that the exposure of 100 mg (14 days/28 day-cycle) in Japanese participants
was higher and almost within the range of that of 200 mg in Caucasian participants. Taking into 
consideration accumulated PK and safety data in Japanese participants, the safety run-in was first 
conducted in Japanese participants by the dose-escalation from 100 mg to 200 mg (14 days/28 
day-cycle) to determine a recommended Phase 3 dose for Asian (including Japanese) participants 
in the Global Phase 3 study. As a result, the 200-mg dose (14 days/28 day-cycle) for 
angioimmunoblastic T-cell lymphoma (ORACLE Study) was recommended by the Independent 
Data Monitoring Committee (IDMC) and chosen as a Phase 3 dose for Asian (including Japanese) 
participants based on the safety, tolerability, and PK profiles, where the exposure of 200 mg for 
14 days in Japanese participants were indicated to be comparable with 300 mg for 14 days in 
Caucasian participants. 
Based on these data, the dose and schedule of 200 mg CC-486 orally administered QD for the first 
14 days of every 28-day treatment cycle were selected for evaluation in the current study.
6
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
6.1
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
1) Signed Written Informed Consent
a) Participants must have signed and dated an Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC)-approved written informed consent form (ICF) in accordance with 
regulatory, local, and institutional guidelines. This must be obtained before the 
performance of any protocol-related procedures that are not part of normal patient care.
b) Participants must be able to adhere to the study visit schedule and other protocol 
requirements.
2) Type of Participant and Target Disease Characteristics
a) Newly diagnosed, histologically confirmed de novo AML or AML secondary to prior MDS
or CMML.
b) Participants should have undergone induction therapy with intensive chemotherapy with 
or without consolidation therapy as recommended in appropriate guideline(s) or equivalent 
regimen according to institutional standard: Must have achieved first CR/CRi status within 
4 months (± 7 days) prior to randomization, as evidenced by the following:
Complete Remission (CR)
Complete Remission with Incomplete Blood 
Count Recovery (CRi)

< 5% blasts in bone marrow  

absence of blasts with Auer rods

absence of extramedullary disease

independent of blood transfusions

< 5% blasts in bone marrow

absence of blasts with Auer rods

absence of extramedullary disease

independent of blood transfusions
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c) ECOG performance status of 0, 1, 2, or 3.
3) Age of Participant
Participant must be ≥ 55 years of age inclusive at the time of signing the informed consent.
4) Reproductive Status
a) A Women of childbearing potential (WOCBP) is a female who: 1) has achieved menarche 
at some point; 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has 
not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out 
childbearing potential) for at least 24 consecutive months (ie, has had menses at any time 
in the preceding 24 consecutive months) and must
i)
Have two negative pregnancy tests as verified by the Investigator prior to starting study 
therapy and must agree to ongoing pregnancy testing during the study and after end of 
study therapy. This applies even if the participant practices true abstinence* from 
heterosexual contact.
ii) Either commit to true abstinence* from heterosexual contact (which must be reviewed 
on a monthly basis and source documented) or agree to use, and be able to comply with, 
highly effective contraception without interruption - 28 days prior to starting 
investigational product, during study therapy (including dose interruptions), and for 6 
months after discontinuation of study therapy, or longer if required by local regulations. 
Contraception requirements are detailed in Appendix 4.
b) Male participants must practice true abstinence* (which must be reviewed on a monthly 
basis) or agree to use a condom during sexual contact with a pregnant female or a female 
of childbearing potential while participating in the study, during dose interruptions, and for 
at least 3 months following investigational product discontinuation, or longer if required 
by local regulations, even if the male participant has undergone a successful vasectomy.
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the 
participant. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) 
and withdrawal are not acceptable methods of contraception.
6.2
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1) Medical Conditions
a) Suspected or proven acute promyelocytic leukemia (FAB M3) based on morphology, 
immunophenotype, molecular assay, or karyotype or AML with previous hematologic 
disorder such as chronic myeloid leukemia or myeloproliferative neoplasms, excluding 
MDS and CMML
b) AML associated with inv(16), t(8;21), t(16;16), t(15;17), or t(9;22) karyotypes or 
molecular evidence of such translocations
c) Prior bone marrow or stem cell transplantation

peripheral neutrophil count ≥ 1.0 x 109/L

platelet count ≥ 100 x 109/L

peripheral neutrophil count < 1.0 x 109/L 
or platelet count < 100 x 109/L
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d) Candidate for allogeneic bone marrow or stem cell transplant at screening
e) Have achieved CR/CRi following therapy with hypomethylating agents
f)
Received therapy with hypomethylating agents for MDS and went on to develop AML 
within four months of discontinuing therapy with hypomethylating agents
g) Proven central nervous system leukemia
h) Diagnosis of malignant disease within the previous 12 months (excluding basal cell 
carcinoma of the skin without complications, carcinoma in situ of the cervix or breast, or 
other local malignancy excised or irradiated with a high probability of cure)
i)
Unstable angina, significant cardiac arrhythmia, or New York Heart Association Class 3 
or 4 congestive heart failure
j)
Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing 
signs/symptoms related to the infection without improvement despite appropriate 
antibiotics or other treatment)
i)
In the case of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection, symptoms must have completely resolved and based on Investigator 
assessment in consultation with the Medical Monitor, there are no sequelae that would 
place the participant at a higher risk of receiving investigational treatment.
2) Prior/Concomitant Therapy
a) Participant used any investigational agents or therapy within 28 days or 5 half-lives prior 
to Day 1 of Cycle 1, whichever is longer
i)
Participants currently in other interventional or investigational vaccine trials may not 
participate in Bristol-Myers Squibb (BMS) clinical trials until the washout period is 
achieved.
b) Participant has received live attenuated vaccines or live COVID-19 vaccines within 30 
days prior to initiation of study treatment
c) Inability to comply with restrictions and prohibited treatments as listed in Section 7.7: 
Concomitant Therapy.
3) Physical and Laboratory Test Findings
a) Participant has any of the following laboratory abnormalities:
i)
Absolute neutrophil count (ANC) < 0.5 x 109/L
ii) platelet count < 20 x 109/L
iii) Serum bilirubin > 1.5 times the upper limit of normal (ULN)
iv) Serum aspartate aminotransferase or alanine aminotransferase > 2.5 times the ULN
v) Serum creatinine > 2.5 times the ULN
b) Known active viral infection with known human immunodeficiency virus (HIV) or active 
chronic hepatitis B virus (HBV) or hepatitis C virus (HCV)
i)
Participants who are hepatitis B surface antigen (HBsAg) negative and HBV viral DNA 
negative are eligible
ii) Participants who had hepatitis B but have received an antiviral treatment and show 
nondetectable viral DNA for 6 months are eligible
iii) Participants who are seropositive because of HBV vaccine are eligible
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iv) Participants who had HCV infection but have received an antiviral treatment and show 
no detectable HCV viral RNA for 6 months are eligible
4) Allergies and Adverse Drug Reaction
a) Known or suspected hypersensitivity to azacitidine or mannitol
5) Other Exclusion Criteria
a) Participant has any significant medical condition, active infection (including SARS-CoV-
2 suspected or confirmed), laboratory abnormality, or psychiatric illness that would prevent 
participation in the study.
i)
In the case of prior SARS-CoV-2 infection, symptoms must have completely resolved 
and based on investigator assessment in consultation with the Medical Monitor, there 
are no sequelae that would place the participant at a higher risk of receiving 
investigational treatment.
(1) A participant who is excluded for SARS-CoV-2 infection could be rescreened.
(2) Additionally, a participant who is currently in another interventional trial for 
COVID-19 may not participate in this clinical trial until the protocol-specific 
washout period is achieved.
b) Participant has received live attenuated vaccines or live COVID-19 vaccines within 30
days prior to initiation of study treatment
c) Participant is unwilling or unable to complete patient-reported outcome assessments 
without assistance or with minimal assistance from trained site personnel and/or caregiver
d) Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific 
circumstances and only in countries where local regulations permit, a person who has been 
imprisoned may be included or permitted to continue as a participant. Strict conditions 
apply, and BMS approval is required.)
e) Any condition, including the presence of laboratory abnormalities, which places the 
participant at unacceptable risk if he/she were to participate in the study
f)
Any significant medical condition, laboratory abnormality, or psychiatric illness that would 
interfere with or prevent participation in the study
g) Any condition that confounds the ability to interpret data from the study
h) Any condition causing an inability to swallow tablets
i)
Any condition that would impair absorption of the study medication (ie, short gut, 
malabsorption syndrome)
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria.
6.3
Lifestyle Restrictions
Not applicable. No restrictions are required.
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6.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently randomized in the study/included in the analysis population. 
A minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements, as applicable, and to respond to queries from regulatory authorities. 
Minimal information includes date of consent, demography, screen failure details, eligibility 
criteria, and any serious AEs.
6.4.1
Retesting During Screening or Lead-in Period
Retesting of laboratory parameters and/or other assessments within any single screening or lead-in 
period will be permitted (in addition to any parameters that require a confirmatory value).
The most current result prior to randomization is the value by which study inclusion will be 
assessed, because it represents the participant’s most current clinical state.
Laboratory parameters and/or assessments that are included in Table 2-1, Screening Procedural 
Outline, may be repeated in an effort to find all possible well-qualified participants. Consultation 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant.
Participants who fail eligibility criteria due to low neutrophil count or platelet count or other 
laboratory abnormality can be rescreened as long as this occurs within 4 months (± 7 days) from 
the achievement of CR or CRi status.
7
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), placebo,
procedure(s), or medical device intended to be administered to a study participant according to the 
study protocol.
Study intervention includes both Investigational [Medicinal] Product (IP/IMP) and 
Non-investigational/Auxiliary [Medicinal] Product (Non-IP/Non-IMP/AxMP) as indicated in
Table 7.1-1.
An IP, also known as IMP in some regions, is defined as a pharmaceutical form of an active 
substance or placebo being tested or used as a reference in a clinical study, including products 
already with a marketing authorization but used or assembled (formulated or packaged) differently 
from the authorized form, or used for an unauthorized indication, or when used to gain further 
information about the authorized form.
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as 
IPs/AxMPs. Not applicable for this study.
7.1
Study Interventions Administered
The selection and timing of dose for each participant is as follows:
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Table 7.1-1:
Study Interventions
Arm Name
CC-486
Placebo
Intervention Name
CC-486 
Placebo for CC-486
Type 
Drug
Drug
Dose Formulation
Tablet
Tablet
Unit Dose Strength(s)
200 mg/150 mg
200 mg/150 mg
Dosage Level(s)
200 mg taken for the first 14 days
of each 28-day treatment cycle
200 mg taken for the first 14 days of 
each 28-day treatment cycle
Route of Administration
Oral
Oral
Use
Experimental
Placebo
IMP and Non-IMP/AxMP
IMP 
IMP
Sourcing
Provided centrally by the Sponsor
Provided centrally by the Sponsor 
Packaging and Labeling
Study intervention will be 
provided in blister cards. Each 
blister card will be labeled as 
required per country requirement.
Study intervention will be provided 
in blister cards. Each blister card will 
be labeled as required per country 
requirement.
Abbreviations: AxMP, auxiliary medicinal product; IMP, Investigational Medicinal Product.
Antiemetic medication (not supplied by the Sponsor) may be administered 30 minutes prior to 
each IP dose. Participant will ingest IP with approximately 240 mL of room temperature water.  
Investigational product may be taken on an empty stomach or with food.  If IP is taken in the 
morning, participants may consume their usual breakfast before or after administration.
7.1.1
Best Supportive Care
Best supportive care may be used in combination with study treatment as deemed necessary.  Best 
supportive care in both treatment arms will include, but not be limited to RBC and platelet 
transfusions; use of an ESA; antibiotic, antiviral, and antifungal therapy; nutritional support
(Section 7.7); and granulocyte-colony stimulating factors (G-CSFs) for participants experiencing 
neutropenic infections (Section 7.7). Thus, the risk of not providing participants with appropriate 
care is minimized while providing the potential benefit of maintaining CR/CRi status.
7.2
Method of Study Intervention Assignment
Study using Interactive Response Technology (IRT): All participants will be centrally randomized
using IRT. Before the study is initiated, each user will receive log-in information and directions 
on how to access the IRT.
Study intervention will be dispensed at the study visits as listed in the Schedule of Activities 
(Section 2). 
Enrolled participants, including those not dosed, will be assigned sequential participant numbers. 
Sequential numbering may restart for each participating site because the distinct patient 
identification number will ultimately comprise the site number and participant number. Those 
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enrolled participants meeting inclusion and exclusion criteria will be eligible to be randomized. 
Randomization numbers will be assigned prior to dosing. 
Participants approved for enrollment will be dynamically randomized to receive CC-486 or 
placebo in a 2:1 ratio.  Randomization will be accomplished by an IRT to ensure timely registration 
and randomization. Based on an allocation ratio preserving biased coin minimization, participants
will be stratified by age at time of induction therapy (55 to 64 years or ≥ 65 years); prior history 
of MDS or CMML (Yes / No); cytogenetic risk category at time of induction therapy (Intermediate 
risk / Poor risk); and received consolidation therapy following induction (Yes / No)32.  The random 
treatment assignment will be concealed so that investigators and participants will not know in 
advance the next treatment assignment. 
After randomization, no crossover between the treatment arms will be permitted.  Participants may 
continue to receive randomized study treatment for as long as it is appropriate, provided that all 
protocol-specified re-treatment criteria are met.
7.3
Blinding
This is a double-blind study. Access to treatment codes will be restricted from all participants, and 
site and Sponsor personnel prior to primary database lock with exceptions as specified below.  
Blinding of study treatment assignment is critical to the integrity of this clinical study. However, 
in the event of a medical emergency or pregnancy in an individual participant in which knowledge 
of the IP is critical to the participant's management, the blind for that participant may be broken 
by the investigator. The participant’s safety takes priority over any other considerations in 
determining if a treatment assignment should be unblinded.
Before breaking the blind of an individual participant’s treatment, the investigator should 
determine that the unblinded information is necessary (ie, that it will alter the participant’s 
immediate management). In many cases, particularly when the emergency is clearly not related to 
the IP, the problem may be properly managed by assuming that the participant is receiving the IP. 
It is highly desirable that the decision to unblind treatment assignment be discussed with the 
Medical Monitor, but the investigator always has ultimate authority for the decision to unblind. 
The actual task of unblinding can be delegated by the investigator to a designee assigned the task
on the Delegation of Authority. The Principal Investigator or appointed designee should only call 
in for emergency unblinding after the decision to unblind the participant has been documented.
For this study, the method of unblinding for emergency purposes is IRT.
For information on how to unblind in an emergency, consult the IRT Manual.
In cases of accidental unblinding, contact the Medical Monitor and ensure every attempt is made 
to minimize additional disclosure and the impact of unblinding.
Any request to unblind a participant for nonemergency purposes should be discussed with the 
Medical Monitor.
In case of an emergency, the investigator(s) has unrestricted access to randomization information 
via the IRT and is capable of breaking the blind through the IRT system without prior approval 
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from the Sponsor. Following the unblinding, the Investigator shall notify the Medical Monitor or 
designee that the unblinding took place.
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s intervention 
assignment is warranted. Participant safety must always be the first consideration in making such 
a determination. If the investigator decides that unblinding is warranted, the investigator should 
make every effort to contact the Sponsor prior to unblinding a participant’s intervention
assignment unless this could delay emergency treatment of the participant. If a participant’s 
intervention assignment is unblinded, the Sponsor must be notified within 24 hours after breaking 
the blind. The date and reason that the blind was broken must be recorded in the source 
documentation and case report form (CRF), as applicable.A scientist in the Bioanalysis department 
of BMS (and/or a designee in the external bioanalytical laboratory) will be unblinded to the 
randomized treatment assignments to minimize unnecessary bioanalytical analysis of samples. 
Any results shared by the Bioanalysis group with the Sponsor’s study team will be blinded to 
ensure integrity of the study.
7.4
Dosage Modification
7.4.1
Dose Modifications for Toxicity
Participants should be monitored for toxicity using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0, as a guide for the grading 
of severity.  
If a certain level of toxicity is observed and considered by the investigator to be at least possibly 
related to treatment, IP dosing may be interrupted, delayed, or modified.  The Investigator is 
encouraged to contact the Medical Monitor prior to any treatment adjustment.
A maximum of one dose reduction to a daily dose of 150 mg is permitted in the event of toxicity.  
If toxicity persists, a maximum of one treatment schedule modification from 14 to 7 days (21 days 
to 14 days for those participants whose dose schedule has been extended due to disease 
progression) is permitted in the event of continuing toxicity that does not respond to dose 
reduction.  The decision to modify a participant’s treatment schedule from 14 to 7 days (21 days 
to 14 days for those participants whose dose schedule has been extended due to disease 
progression) should first be discussed with the Medical Monitor or designee.  Participants should 
not receive less than 150 mg IP or be scheduled to receive treatment for less than 7 days.  
Participants who have their IP dose reduced or treatment schedule modified may return to their 
original dose and/or schedule in a step-wise fashion upon discussion and agreement between the 
investigator and the Medical Monitor provided that the increased dose or treatment schedule is 
tolerable and at least two additional treatment cycles have occurred since the dose reduction or 
treatment schedule modification.  The treatment schedule should first be increased from 7 to 14 
days, followed by a dose escalation step from 150 to 200 mg.
Dose Modification for Febrile Neutropenia ≥ Grade 3
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Any participant who experiences ≥Grade 3 febrile neutropenia (two consecutive readings of body 
temperature > 38.0°C for 2 hours and an ANC count < 0.5 × 109/L) can continue to receive IP 
uninterrupted at the discretion of the Investigator.  If the febrile neutropenia episode persists for 
≥4 days despite adequate/maximal antibiotic, antiviral, and/or antifungal therapy, IP should be 
temporarily discontinued until the fever has resolved and the ANC has improved or stabilized as 
assessed by the Investigator.  Treatment with IP at the same dose should resume no earlier than 3 
days following the resolution of the fever.  If a participant experiences febrile neutropenia in 2 
consecutive cycles, the steps noted above should be followed, but the IP dose should be reduced 
to 150 mg upon resumption of treatment with IP.  A treatment schedule modification from 14 to 7 
days (21 days to 14 days for those participants whose dose schedule has been extended due to 
disease progression) of treatment may be warranted if a participant experiences regular episodes
of febrile neutropenia that are deemed by the Investigator to be related to IP.  
Dose Modification for Diarrhea ≥ Grade 3
It is recommended that participants experiencing diarrhea be managed according to the guidelines 
provided in Appendix 7.  Antidiarrheal medication may be administered as prophylaxis against 
diarrhea and for treatment of any AEs of diarrhea.  Dose modifications for diarrhea are summarized 
in Table 7.4.1-1.  For participants not having problems during the first two cycles, the treating 
physician may discontinue use of antiemetic medications.
Dose Modification for Nausea and Vomiting ≥ Grade 3
A serotonin (5-HT3) receptor antagonist (eg, ondansetron or other comparable medication) should 
be administered as an antiemetic approximately 30 minutes prior to administration of IP.  
Antiemetic medication(s) should be administered for treatment of any AEs of nausea and/or 
vomiting.  If there has been no nausea and/or vomiting during the first two cycles, the Investigator 
may choose to omit the antiemetic as required, provided this is clearly documented in the CRF.  
Dose modifications for nausea and vomiting are summarized in Table 7.4.1-1.
Dose Modification for Renal Dysfunction and Abnormal Serum Electrolytes
If unexplained elevations of blood urea nitrogen (BUN) and/or serum creatinine (> 20%) occur 
(per Investigator), the next cycle of treatment should be delayed until values return to baseline,
and the dose should be reduced to 150 mg in the next cycle of treatment.  A schedule modification 
from 14 to 7 days (21 days to 14 days in those participants whose dose schedule has been extended 
due to disease progression) can be made if the elevation in BUN and/or creatinine recurs in the 
subsequent cycle.  Should similar unexplained renal disturbances subsequently persist or recur 
during the next cycle of treatment, study treatment should be discontinued.
Dose Modification for Other Treatment-Related Non-hematologic Toxicity ≥ Grade 3
Any participant who experiences a treatment-related non-hematologic toxicity Grade 3 or higher 
that is an escalation from baseline status (prior to first IP dose) should temporarily discontinue IP 
treatment until the toxicity returns to Grade 2 or lower.  Dose modifications for Grade 3 or higher 
non-hematologic toxicity are summarized in Table 7.4.1-1.
Dose Modification for Weight Change
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No dose adjustment should be made for weight loss or gain alone; however, the reason for weight 
loss (eg, significant nausea, vomiting, anorexia, etc) or weight gain (eg, peripheral edema) should 
be investigated and may require a dose modification as specified in Table 7.4.1-1. 
Table 7.4.1-1:
Guidelines for Dose Modifications
NCI-CTCAE 
Toxicity Grade
Action
Febrile Neutropenia 
(≥Grade 3)

Continue CC-486 at the discretion of the Investigator

If episode persists for ≥ 4 days despite adequate / maximal 
antibiotic, antiviral, and/or antifungal therapy, CC-486 should 
be temporarily discontinued until the fever has resolved.

Resume CC-486 at the same dose after the fever has resolved 
and the ANC has improved or stabilized (as assessed by the 
Investigator).  CC-486 should not be resumed for at least 3 days 
following resolution of fever.

If a participant experiences febrile neutropenia in 2 consecutive 
cycles, the steps noted above should be followed, but the CC-486 
dose should be reduced to 150 mg upon resumption of treatment 
with CC-486.

If participant continues to experience febrile neutropenia episodes 
that are deemed to be related to CC-486 by the Investigator, a 
treatment schedule modification from 14 to 7 days (21 days to 14 
days for those participants whose dose schedule has been extended 
due to disease progression) of treatment may also be warranted.  
(Treatment schedule modification requires prior discussion with 
Medical Monitor.)
Diarrhea (≥Grade 
3)

Interrupt CC-486 and provide adequate/maximum medical 
intervention.

Resume CC-486 at same dose when toxicity resolves to ≤Grade 1.

If event reoccurs upon rechallenge or during next treatment cycle, 
reduce CC-486 dose to 150 mg.

If event reoccurs at same intensity once dose is reduced to 150 mg, 
follow the steps above and modify treatment schedule from 14 to 7 
days (21 days to 14 days for those participants whose dose schedule 
has been extended due to disease progression) of CC-486 
administration. (Treatment schedule modification requires prior 
discussion with Medical Monitor.)
Nausea and/or 
Vomiting  
(≥Grade 3)

Interrupt CC-486 and provide adequate/maximal 
medical 
intervention.

Resume CC-486 at same dose when toxicity resolves to ≤Grade 1.
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Table 7.4.1-1:
Guidelines for Dose Modifications
NCI-CTCAE 
Toxicity Grade
Action

If event reoccurs upon rechallenge or at same intensity during next 
treatment cycle, reduce dose to 150 mg. (Treatment schedule 
modification requires prior discussion with Medical Monitor.)
Renal Dysfunction

For unexplained elevations of BUN and/or serum creatinine from 
baseline level (> 20%), hold CC-486 if this is apparent during the 
CC-486 administration phase and/or delay the start of the next cycle 
of treatment until values return to baseline (± 20%).  Reduce CC-
486 dose in the next cycle of treatment to 150 mg.

Discontinue CC-486 if similar unexplained renal and/or electrolyte
disturbances subsequently persist or recur during the next cycle of 
treatment. (Treatment schedule modification requires prior 
discussion with Medical Monitor.)
Other Grade 3 
Non-hematological 
Treatment-related 
AEs

Interrupt CC-486 dosing and provide medical intervention as 
appropriate.

Resume CC-486 at same dose when toxicity resolves to ≤Grade 2.

If event reoccurs upon rechallenge or at same intensity during next 
treatment cycle, reduce CC-486 dose to 150 mg.

If event reoccurs at same intensity once dose is reduced to 150 mg, 
follow the steps above and modify treatment schedule from 14 to 7 
days (21 days to 14 days for those participants whose dose schedule 
has been extended due to disease progression) of CC-486 
administration.  (Treatment schedule modification requires prior 
discussion with Medical Monitor.)
Abbreviations: AE, adverse event; ANC, absolute neutrophil count; BUN, blood urea nitrogen; NCI-CTCAE, National 
Cancer Institute Common Terminology Criteria for Adverse Events.
7.4.2
Dose and Schedule Adjustment in Participants with AML 
Relapse/Progression
In participants on study who have subsequent evidence of AML relapse with blasts ≥5%, either 
in the peripheral blood count or bone marrow, and provided the blasts are no greater than 15% in 
the blood or bone marrow, escalation of the dosing regimen (dose and/or schedule) can be 
implemented as follows (provided it is in the best interest to do so as judged by the Investigator):

Participant currently on blinded treatment of CC-486 200 mg or placebo QD for 14 days —
escalate schedule to CC-486 200 mg or placebo QD for 21 days

Participant currently on blinded treatment of CC-486 150 mg or placebo QD for 14 days —
escalate dose schedule, as a first step, to CC-486 150 mg or placebo QD for 21 days and then 
escalate dose to CC-486 200 mg or placebo QD for 21 days
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Participant currently on blinded treatment for CC-486 150 mg or placebo QD for 7 days -
escalate dose schedule, as a first step, to CC-486 150 mg or placebo QD for 14 days and then 
escalate dose to CC-486 200 mg or placebo QD for 14 days
In cases where relapse is noted within a week of starting the next cycle, and there is a desire to 
escalate the dose schedule during the cycle, contact the Medical Monitor to discuss this, in order 
to obtain the additional required IP.
7.4.3
Re-treatment Criteria
Prior to the start of each cycle, participants will have laboratory assessments performed to evaluate
organ function.  To proceed to the next cycle, participants must continue to meet entry criteria 
regarding renal and hepatic function (see Section 6.2).  Thus, participants will have laboratory 
assessments performed to evaluate organ function prior to starting each cycle (including Cycle 1).  
Because of the time it takes to obtain results from the central laboratory, samples should be 
collected early enough prior to starting the next cycle to allow sufficient time for review.  In the 
event that immediate laboratory assessment is needed, local laboratory measurement is acceptable 
for starting the next cycle pending the outcome of the central laboratory assessment (ie, in addition 
to collecting the local laboratory sample, a second sample should be collected and sent to the 
central laboratory).
The start of the next cycle will be delayed if the participant does not meet entry criteria regarding 
renal and hepatic function.  If there is a delay of more than 42 days (6 weeks) in the start of the 
next cycle, the Medical Monitor must be consulted.  Study treatment should be discontinued if 
there is a delay of more than 56 days (8 weeks) in the start of the next cycle unless, in the opinion 
of the investigator and the Medical Monitor, the participant is experiencing clinical benefit.  
Justification for the participant continuing in the study must be recorded in the source documents.
Prior to discontinuing a participant for reasons other than those listed in Section 8.1, the 
investigator should contact the Medical Monitor and forward appropriate supporting documents 
for review and discussion.
7.5
Preparation/Handling/Storage/Accountability
The IP/AxMP must be stored in a secure area according to local regulations. It is the responsibility 
of the investigator, or designee where permitted, to ensure that IP/AxMP is only dispensed to study 
participants. The IP/AxMP must be dispensed only from official study sites by authorized 
personnel according to local regulations.
The product storage manager should ensure that the study intervention is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. If 
concerns regarding the quality or appearance of the study intervention arise, the study intervention
should not be dispensed, and BMS should be contacted immediately.
Study intervention not supplied by BMS will be stored in accordance with the package insert.
IP/AxMP documentation (whether supplied by BMS or not) must be maintained that includes all 
processes required to ensure the drug is accurately administered. This includes documentation of 
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drug storage, administration and, as applicable, storage temperatures, reconstitution, and use of 
required processes (eg, required diluents, administration sets).

The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are reported 
and resolved before use of the study intervention.

The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).

Further guidance and information for the final disposition of unused study interventions are 
provided in Appendix 2.
7.6
Treatment Compliance
Study intervention compliance will be periodically monitored by drug accountability. Drug 
accountability should be reviewed by the site study staff at each visit to confirm treatment 
compliance. Sites should discuss discrepancies with the participant at each on-treatment study 
visit. 

When participants self-administer study intervention(s) at home, compliance with study 
intervention will be assessed at each visit. Compliance will be assessed by direct questioning, 
counting returned tablets, etc during the site visits and documented in the source documents 
and relevant forms. Deviation(s) from the prescribed dosage regimen should be recorded in the 
CRF.

A record of the quantity of CC-486 dispensed to and administered by each participant must be 
maintained and reconciled with study intervention and compliance records.  Intervention start 
and stop dates, including dates for intervention delays and/or dose reductions, will also be 
recorded in the CRF.
7.7
Concomitant Therapy
7.7.1
Prohibited and/or Restricted Treatments
All prior and concomitant medications (prescription and nonprescription) that are administered 
from Cycle 1 Day 1 up to 28 days after the last dose of IP or up to the Treatment Discontinuation 
Visit, whichever period is longer, must be recorded on the appropriate CRF.  Significant nondrug 
therapies and concomitant procedures administered following the first dose of IP through the last 
dose of IP or up to the Treatment Discontinuation Visit, whichever period is longer, must be 
recorded on the appropriate CRF.
Prior treatment with ESAs, thrombopoiesis-stimulating agents (TSAs), iron-chelation therapy, and 
other medications considered supportive care for AML should be recorded, regardless of 
discontinuation date of treatment.
Live COVID-19 vaccines should not be administered to a participant during the study, including 
during treatment, during the Safety Follow-up Period, and within 3 months following the last dose 
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of IMP. In addition, the administration of a live COVID-19 vaccine is prohibited up to 30 days 
prior to initiation of study treatment.
Concomitant medications should be kept to a minimum during the study.  However, if considered 
necessary for the participant’s welfare and are unlikely to interfere with the IP, they may be given 
at the discretion of the investigator.
7.7.1.1
Permitted Concomitant Medications and Procedures
Best supportive care may be used in combination with study treatment as deemed necessary.  Best 
supportive care in both treatment arms will include, but not be limited to RBC and platelet 
transfusions; use of an ESA; antibiotic, antiviral, and antifungal therapy; nutritional support; and 
granulocyte-colony stimulating factors (G-CSFs) for participants experiencing neutropenic 
infections. Thus the risk of not providing participants with appropriate care is minimized.  The use 
of these products will be considered as concomitant treatment and documented as concomitant 
medications, therapies, or procedures.
The use of myeloid growth factors, G-CSFs, and granulocyte macrophage colony-stimulating 
factors [GM-CSFs]) may be given per Investigator’s discretion.  For participants who develop an 
ANC < 0.5 x 109/L, administration of prophylactic fluoroquinolone antibiotics (eg, ciprofloxacin 
or levofloxacin) or other prophylactic antibiotic treatments used as standard treatment at the site is 
allowed and must be documented as a concomitant medication on the appropriate CRF.  If 
neutropenic infection occurs, treatment should consist of a broad-spectrum antibiotic, and if the 
Investigator deems the use of a myeloid growth factor to be medically important, myeloid growth 
factors may also be administered.  If myeloid growth factors are administered, they should be 
stopped within 4 days following resolution of the febrile episode.  In addition, the participant’s 
response to protocol-defined treatment should not be assessed until at least 3 weeks following the 
last dose of myeloid growth factor to avoid confusing relapse of disease, when it may have been 
related to growth factor.
A serotonin (5-HT3) receptor antagonist (eg, ondansetron or other comparable medication) should 
be administered as an antiemetic approximately 30 minutes prior to administration of IP.  
Pretreatment or post treatment with a serotonin (5-HT3) receptor antagonist (or other antiemetic 
medication) will be considered as concomitant therapy and should be recorded on the appropriate 
CRF.
COVID-19 vaccines that have been authorized by an appropriate regulatory agency and are NOT 
live or attenuated (not capable of transmitting infectious virus) are acceptable and should be 
handled in the same manner as other vaccines approved for immunocompromised cancer subjects. 
COVID-19 vaccines that are NOT live can be administered during the study. If possible, 
Investigators are encouraged to give the vaccine at least 24 to 72 hours prior to starting study drugs 
(to watch for and manage vaccine-related acute toxicities).
Non-live COVID-19 vaccination is considered a simple concomitant medication within the study. 
However, the efficacy and safety of non-live vaccines (including non-live COVID-19 vaccines) in 
subjects who are taking the study drugs in this trial, are unknown.
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7.7.1.2
Prohibited Concomitant Medications and Procedures
The following concomitant medications are specifically excluded during the study:

Cytotoxic chemotherapeutic agents or experimental agents

Romiplostim and other TSAs (eg, interleukin-11)

Hydroxyurea

Lenalidomide

Pomalidomide

Thalidomide

Arsenic trioxide

Interferon

Retinoids

Live COVID-19 vaccines should not be administered to a participant during the study, 
including treatment, during the Safety Follow-up Period, and within 3 months following the 
last dose of IMP. In addition, the administration of a live COVID-19 vaccine is prohibited up 
to 30 days prior to initiation of study treatment.
7.7.2
Other Restrictions and Precautions
Participants are prohibited from joining another clinical trial while they are participating in this 
study.
7.8
Continued Access to Study Intervention After the End of the Study
At the conclusion of the study, if the study intervention is not available as an approved treatment 
in the local country, participants who continue to demonstrate clinical benefit will be eligible to 
receive BMS-supplied study intervention for maximum treatment duration as specified in Section 
7.1.
If the study treatment is not available as an approved and available treatment, study intervention 
will be provided via an extension of the study, a rollover study requiring approval by the 
responsible Health Authority and ethics committee, or through another mechanism at the discretion 
of BMS.
BMS reserves the right to terminate access to BMS-supplied study intervention if any of the 
following occur: a) the study is terminated due to safety concerns; b) the development of CC-486
is terminated for other reasons, including, but not limited to, lack of efficacy and/or not meeting 
the study objectives; c) the participant can obtain medication from a government-sponsored or 
other health program. In all cases, BMS will follow local regulations.
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8
DISCONTINUATION CRITERIA
8.1
Discontinuation From Study Intervention
Participants MUST discontinue IP (and Non-IP/AxMP at the discretion of the investigator) for any 
of the following reasons:

Disease relapse 
Participants will be discontinued from treatment when they meet the following criteria:

Appearance of > 15% blasts in the bone marrow or peripheral blood

The above occurrence should be attributed to relapse following CR/CRi, and not 
attributable to any other cause (eg, bone marrow regeneration after consolidation therapy 
or myeloid growth factor administration).

Participant’s request to stop study intervention. Participants who request to discontinue study 
intervention will remain in the study and must continue to be followed for protocol-specified 
follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by the participant 
to provide this information

Any clinical AE, laboratory abnormality, or intercurrent illness which, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
participant

Participant withdraws from active treatment but continues follow-up

Participant becomes eligible (per Investigator) for allogeneic bone marrow or stem cell 
transplantation during the treatment period

Death

Loss to follow up

Protocol violation

Termination of the study by BMS

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness. (Note: Under 
specific circumstances and only in countries where local regulations permit, a participant who 
has been imprisoned may be permitted to continue as a participant. Strict conditions apply, and 
BMS approval is required.)
Refer to the Schedule of Activities for data to be collected at the time of treatment discontinuation 
and follow-up and for any further evaluations that can be completed.
All participants who discontinue study intervention should comply with protocol-specified 
follow-up procedures as outlined in Section 2. The only exception to this requirement is when a 
participant withdraws consent for all study procedures, including post-treatment study follow-up,
or loses the ability to consent freely (eg, is imprisoned or involuntarily incarcerated for the 
treatment of either a psychiatric or physical illness). Additionally, all participants who are 
discontinued from protocol-prescribed treatment will be followed for a period of 28 days following 
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the last dose of IP or until the date of the last study visit, whichever is later, for the collection of 
AEs. Discontinued participants will not be replaced.
If study intervention is discontinued prior to the participant’s completion of the study, the reason 
for the discontinuation must be documented in the participant’s medical records per local 
regulatory requirements in each region/country and entered on the appropriate CRF page.
8.1.1
Post-study Intervention Study Follow-up
In this study, RFS is the primary endpoint of the study. Post-study follow-up is of critical 
importance and is essential to preserving participant safety and the integrity of the study. 
Participants who discontinue study intervention must continue to be followed (in this study or a 
rollover study) for collection of outcome and/or survival follow-up data as required and in line 
with Section 5 until death or the conclusion of the study.
8.2
Discontinuation From the Study
Participants who request to discontinue study intervention will remain in the study and must 
continue to be followed for protocol-specified follow-up procedures. The only exception to this is 
when a participant specifically withdraws consent for any further contact with him/her or persons 
previously authorized by participant to provide this information. 

Participants should notify the investigator of the decision to withdraw consent from future 
follow-up.

The withdrawal of consent should be explained in detail in the medical records by the 
investigator, as to whether the withdrawal is from further treatment with study intervention
only or also from study procedures and/or post-treatment study follow-up, and entered on the 
appropriate CRF page.

In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law.

If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
8.2.1
Individual Discontinuation Criteria

A participant may withdraw completely from the study at any time at his/her own request, or 
may be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. This is expected to be uncommon. Stopping study 
intervention is not considered withdrawal from the study.

At the time of discontinuing from the study, if possible, an early termination visit should be 
conducted, as shown in the Schedule of Activities. See the Schedule of Activities for data to 
be collected at the time of study discontinuation and follow-up and for any further evaluations 
that need to be completed.
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
The participant will be permanently discontinued both from the study intervention and from 
the study at that time.

If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
8.3
Lost to Follow-up
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit:

All reasonable efforts must be made to locate participants to determine and report their ongoing 
status. This includes follow-up with persons authorized by the participant.

Lost to follow-up is defined by the inability to reach the participant after a minimum of 
three (3) documented phone calls, faxes, or emails, as well as lack of response by participant
to one (1) registered mail letter. All attempts should be documented in the participant’s medical 
records.

If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death.

If the investigator’s use of third-party representative to assist in the follow-up portion of the 
study has been included in the participant’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining the participant’s 
contact information or other public vital status data necessary to complete the follow-up 
portion of the study. 

The site staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information.

If, after all attempts, the participant remains lost to follow-up, then the last known alive date 
as determined by the investigator should be reported and documented in the participant’s 
medical records.
9
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and timing are summarized in the Schedule of Activities. 

Protocol waivers or exemptions are not allowed.

All immediate safety concerns must be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
treatment.

Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria before randomization. The investigator will maintain a 
screening log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.
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
Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of informed consent may be utilized for screening or baseline 
purposes provided the procedure meets the protocol-defined criteria and has been performed 
within the time frame defined in the Schedule of Activities.

Safety/laboratory/analyte results that could unblind the study will not be reported to 
investigative sites or other blinded personnel until the study has been unblinded.
9.1
Efficacy Assessments
9.1.1
Efficacy Assessment for the Study
International Working Group Response
International Working Group (IWG) response assessment will be assessed at Cycles 3, 6, 9, 12, 
15, 18, 21, 24, 30, 36, and the Treatment Discontinuation Visit.  After Cycle 36, IWG response 
assessment will be performed if clinically indicated at the discretion of the Investigator.  
Participants should be assessed for CR/CRi status maintenance or disease relapse.
Bone Marrow Aspirate, Biopsy, and Peripheral Blood Smear
Bone marrow aspirate (or biopsy if adequate aspirate is not attainable) samples during the Double-
blind Treatment Phase should be collected at Screening, on Day 1 (± 7 days) of Cycles 3, 6, 9, 12, 
15, 18, 21, 24, 30, 36, and the Treatment Discontinuation Visit.  After Cycle 36, bone marrow 
aspirate collection and evaluation will occur if clinically indicated at the discretion of the 
Investigator.
Additional bone marrow samples should be collected as clinically indicated.  A bone marrow 
biopsy must be collected if adequate aspirate is not attainable.  Whenever a bone marrow sample 
is collected, a peripheral blood smear is to be prepared.
Instructions for submission of bone marrow samples are provided in Study Reference Manual 
and/or Study Central Laboratory Manual.
Cytogenetics
Bone marrow cytogenetic testing is to be completed whenever a bone marrow aspirate (or biopsy 
if adequate aspirate is not attainable; note that specific handling of the biopsy is required if it is to 
be used for cytogenetics testing [refer to the Laboratory Manual for sample collection, handling, 
and processing instructions]).
Follow-up AML Therapies
All discontinued participants, regardless of reason for discontinuation, should be followed for 
subsequent AML therapies every month for the first year and every 3 months thereafter until death, 
loss to follow-up, withdrawal of consent from further follow-up, or study closure.  Subsequent 
AML therapy follow-up can be performed via the telephone.
Survival Follow-up
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All discontinued participants, regardless of reason for discontinuation, should be followed for 
survival every month for the first year and every 3 months thereafter until death, loss to follow-
up, withdrawal of consent from further follow-up, or study closure.  The survival follow-up can 
be performed via telephone.
9.1.2
Health-related Quality of Life
The evaluation of patient-reported outcomes (PROs) is an increasingly important aspect of clinical 
efficacy in oncology trials. Such data provide an understanding of the impact of treatment from 
the subject’s perspective and offer insights into patient experience that may not be captured 
through physician reporting. Additionally, generic health-related quality of life (HrQoL) measures 
provide data needed for calculating utility values to inform health economic models. Health-related 
quality of life (HRQoL) instruments Functional Assessment of Chronic Illness Therapy (FACIT) 
Fatigue Scale and the EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L) will be completed 
by participants throughout the trial. The questionnaire should be completed by the participant
before any clinical assessments are performed at any given visit (refer to Table 2-2 and Table 2-
3). If a participant will not complete one or more questionnaires, the reason for this will be 
documented. Questionnaires should be completed in the language most familiar to each 
participant, and participants should be given adequate time and space to complete the 
questionnaire. If the participant withdraws from the study prematurely, all attempts should be made 
to obtain a final quality-of-life questionnaire prior to participant discontinuation.
The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale is a subscale of the 
FACIT and has been validated in the oncology setting (Appendix 8)33 34. The items are measured 
on a response scale with five options (0 = not at all to 4 = very much) and has a 7-day recall period.
The 13-question subscale has scores that range from 0 to 52, with higher scores indicating less 
fatigue.  Quality of life scores on these FACIT scales significantly decline as patient performance 
status worsens.  Interventions that reverse fatigue should have a positive effect on quality of life.  
Participants’ reports of general health status will be assessed using the EQ-5D-5L questionnaire
(Appendix 9)35. The EQ-5D-5L has 2 components: a descriptive system and a visual analog scale 
(VAS). The instrument’s descriptive system consists of 5 dimensions: mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression. Each dimension describes 5 levels of 
problems, including “no,” “slight,” “moderate,” “severe,” and “extreme” or “unable to.” A 
dimension for which there are no problems is said to be at level 1, while a dimension for which 
there are extreme problems is said to be at level 5. Thus, the numbers 11111 and 55555 represent 
the best health state and the worst health state, respectively, described by the EQ-5D-5L. 
Altogether, the instrument describes 55 = 3,125 health states. Empirically, derived weights can be 
applied to an individual’s responses to the EQ-5D-5L to generate a utility index measuring the 
value to society of his or her current health. In addition, a VAS allows respondents to rate their 
own current health on a 101-point scale ranging from 0 = “worst imaginable” to 100 = “best 
imaginable.” The EQ-5D-5L takes approximately 5 minutes to complete.
9.2
Adverse Events
The definitions of an AE or SAE can be found in Appendix 3.
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AEs will be reported by the participant.
The investigator and any qualified designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for following up 
on AEs that are serious, considered related to the study intervention or the study, or that caused 
the participant to discontinue before completing the study. 
Refer to Appendix 3 for SAE reporting.
9.2.1
Time Period and Frequency for Collecting AE and SAE Information
All SAEs and non-serious AEs must be collected from the time of signing the consent, including 
those thought to be associated with protocol-specified procedures, and within 28 days following 
discontinuation of dosing or until the End of Treatment Visit, whichever is later.
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study intervention or protocol-specified procedure.

Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the appropriate section of the CRF module.

All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated 
in Appendix 3. 

The investigator will submit any updated SAE data to the Sponsor or designee within 24 hours
of updated information being available.
Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the investigator learns of any SAE, including a death, at any time after a participant 
has been discharged from the study, and he/she considers the event reasonably related to the study 
intervention or study participation, the investigator must promptly notify the Sponsor.
The method of evaluating and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in Appendix 3.
9.2.2
Method of Detecting AEs and SAEs
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a participant. Care should be taken not to introduce bias when collecting AEs and/or 
SAEs. Inquiry about specific AEs should be guided by clinical judgement in the context of known 
AEs, when appropriate for the program or protocol.
9.2.3
Follow-up of AEs and SAEs

Non-serious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Appendix 3).

Follow-up is also required for non-serious AEs that cause interruption or discontinuation of 
study intervention and for those present at the end of study intervention as appropriate.

All identified non-serious AEs must be recorded and described on the non-serious AE page of 
the CRF (paper or electronic). Completion of supplemental CRFs may be requested for AEs 
and/or laboratory abnormalities that are reported/identified during the course of the study.
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After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs, and non-serious AEs of special interest (as defined in 
Section 9.2) will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the participant is lost to follow-up (as defined in Section 8.3).
Further information on follow-up procedures is given in Appendix 3.
9.2.4
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
product under clinical investigation are met.

An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with 
the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to local 
requirements.
The Sponsor or designee must report AEs to regulatory authorities and ethics committees 
according to local applicable laws and regulations. A SUSAR (suspected, unexpected serious 
adverse reaction) is a subset of SAEs and must be reported to the appropriate regulatory authorities 
and investigators following local and global guidelines and requirements.
9.2.5
Pregnancy
If, following initiation of the study intervention, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including during at least for 6
months after study product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance Form 
to the BMS designee within 24 hours of awareness of the event and in accordance with SAE 
reporting procedures described in Appendix 3. If a female partner of a male participant taking IP 
becomes pregnant within 3 months after the male participant’s last dose of IP, the male participant
taking IP should notify the Investigator, and the pregnant female partner should be advised to call 
her health care provider immediately.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information, must be reported on the Pregnancy 
Surveillance Form. Protocol-required procedures for study discontinuation and follow-up must be 
performed on the participant.
9.2.6
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the non-serious AE CRF 
page or SAE eCRF, as appropriate. Paper forms are only intended as a back-up option when the 
electronic system is not functioning.

Any laboratory test result that is clinically significant or meets the definition of an SAE 

Any laboratory test result abnormality that required the participant to have study intervention
discontinued or interrupted
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Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy
It is expected that, wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia vs low hemoglobin value).
9.2.7
Potential Drug-induced Liver Injury
Drug-induced liver injury (DILI) has not been associated with CC-486. Specific criteria for 
identifying a potential DILI have not been identified for this protocol. Standard medical practice 
in identifying and monitoring hepatic issues should be followed.
9.2.8
Other Safety Considerations
Any significant worsening of conditions noted during interim or final physical examinations, 
electrocardiogram, x-ray filming, or any other potential safety assessment required or not required 
by the protocol should also be recorded as a non-serious AE or SAE, as appropriate, and reported 
accordingly.
9.3
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. Overdoses that meet the regulatory 
definition of SAE will be reported as an SAE (see Appendix 3). If an overdose is associated with
an AE, the overdose and AE should be reported as separate terms.
9.4
Safety
Planned time points for all safety assessments are listed in the Schedule of Activities.
9.4.1
Physical Examinations
Refer to Schedule of Activities.
9.4.2
Vital Signs
Refer to Schedule of Activities.
9.4.3
Electrocardiograms
Refer to Schedule of Activities.
9.4.4
Clinical Safety Laboratory Assessments
Investigators must document their review of each laboratory safety report.
Table 9.4.4-1:
Clinical Laboratory Assessments
Hematology
Hemoglobin
Hematocrit
WBC count with differential
Absolute neutrophil count
Platelet count
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Table 9.4.4-1:
Clinical Laboratory Assessments
RBC count
MCV, MCH, MCHC
Chemistry
Aspartate aminotransferase
Alanine aminotransferase 
Direct/indirect total bilirubin
Alkaline phosphatase
Lactate dehydrogenase 
Creatinine
Blood urea nitrogen 
Uric acid
Glucose
Total protein
Albumin
Sodium
Potassium
Magnesium
Chloride
Calcium
Phosphorus
Bicarbonate
Urinalysis
A standard urinalysis (including microscopic analysis if indicated; screening and whenever clinically indicated in 
the Double-blind Treatment Phase)
Viral Serology
HBsAg, anti-HBs, anti-HBc, hepatitis C antibody, HIV antibody and, if applicable, HBV viral DNA and HCV 
viral RNA testing by PCR (screening)
Other Analyses
Coagulation, including PT, PTT, INR (screening)
Unstained peripheral blood smear (screening, predose, discharge)
Pregnancy test (WOCBP only: screening, predose, discharge)
Abbreviations: DNA, deoxyribonucleic acid; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, 
hepatitis C virus; HIV, human immunodeficiency virus; INR, international normalized ratio; MCH, mean corpuscular 
hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; PCR, 
polymerase chain reaction; PT, prothrombin time; PTT, partial thromboplastin time; RBC, red blood cell; RNA, 
ribonucleic acid; WOCBP, women of childbearing potential.
9.4.5
Imaging Safety Assessment
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the study investigator as per standard 
medical/clinical judgment.
9.5
Pharmacokinetics
On the PK days (Cycle 1 Day 1 and Cycle 1 Day 14), participants will ingest CC-486 in the clinic 
after performing the required overnight fasting and pre-dose PK sample collection, with each dose 
being given at approximately the same time of day. The exact date and time of dosing and PK 
sampling will be recorded in the source documents and appropriate form. The following PK 
parameter values will be derived by noncompartmental methods by a validated
PK analysis
program for participants with intensive PK sampling.
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Cmax
Maximum observed plasma concentration
Tmax
Time of maximum observed plasma concentration
AUC(0-T)
Area under the plasma concentration-time curve from time zero to time of last
quantifiable concentration
AUC(INF)
Area under the plasma concentration-time curve from time zero extrapolated to infinite
time
Ctrough
Trough observed plasma concentration
T-Half
Terminal elimination half-life
CLT/F
Apparent clearance of drug after extravascular administration
VZ/F
Apparent volume of distribution of terminal phase
Blood samples (3 mL/sample) for oral azacitidine PK assessment will be collected from pre-dose 
to 6 hours after dose administration.
The study sites that can perform intensive PK sampling will perform intensive PK sampling at the 
time points indicated in Table 9.5-1.
Sparse PK sampling will be in the other participants who will not participate in intensive PK 
sampling at the time points indicated in Table 9.5-2.
Table 9.5-1:
Intensive Pharmacokinetic Sampling Schedule for CC-486
Study Day of 
Sample Collection
(1 Cycle = 4 Weeks)
Event
Time Relative to CC-486  Dose 
(hr:min)a
CC-486 PK Plasma Sample
Cycle 1 Day 1
Predose
0:00
X
0:30
X
1:00
X
1:30
X
2:00
X
2:30
X
4:00
X
6:00
X
Cycle 1 Day14
Predose
0:00
X
0:30
X
1:00
X
1:30
X
2:00
X
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Study Day of 
Sample Collection
(1 Cycle = 4 Weeks)
Event
Time Relative to CC-486  Dose 
(hr:min)a
CC-486 PK Plasma Sample
2:30
X
4:00
X
6:00
X
Abbreviations: hr, hours; min, minutes, PK, pharmacokinetic.
a Windows of PK sampling times are as follows: ≤ 60 minutes for predose PK samples; ± 5 minutes for 0.5, 1.0, 1.5, 
2.0 and 2.5 hour PK samples; and ± 10 minutes for 4.0 and 6.0 hours PK samples.
Table 9.5-2:
Sparse Pharmacokinetic Sampling Schedule for All Other 
Participants
Study Day of Sample 
Collection
(1 Cycle = 4 Weeks)
Event
Time Relative to CC-486  Dose 
(hr:min)
CC-486 PK Plasma Sample
Cycle 2 Day 1
0:30 to 6:00
Xa
Cycle 2 Day 1
0:30 to 6:00
Xa
Cycle 3 Day 1
0:30 to 6:00
Xa
Cycle 3 Day 1
0:30 to 6:00
Xa
Abbreviaations: hr, hours; min, minutes, PK, pharmacokinetic.
a PK samples to be collected between 0.5 and 6 hours at least 2 hours apart.
Placebo samples will not be analyzed.
Treatment assignments will be released to the bioanalytical laboratory in order to minimize 
unnecessary analysis and/or reanalysis of PK samples.
Concentration analyses for azacitidine will be performed by validated bioanalytical method(s).
Additionally, residual bioanalytical samples will be archived and may be used for potential 
exploratory bioanalysis (including, but not limited to, metabolite analyses, etc) and/or for 
additional method purposes (including, but not limited to, cross-validation cutpoint, etc). 
Detailed instructions for the PK blood collection, labeling, processing, storage, and shipping will 
be provided to the site in the procedure manual.
9.6
Genetics
At screening and end of treatment, peripheral blood sampling for pharmacogenomic analysis is 
mandatory and participant must consent to the collection of these samples.  Samples should be 
collected when bone marrow is collected at protocol specified time points and must be collected 
on the same day as the bone marrow aspirate procedure.
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Refer to the Laboratory Manual for sample collection, handling, and processing instructions.
Other correlative assessments may include, but are not limited to, AML gene mutation sequencing
and DNA methylation. Results from these studies will be evaluated in association with parameters 
of clinical benefit to determine whether biomarkers of response or non-response to treatment may 
be identified.
9.7
Biomarkers
Collection of samples for other biomarker research is also part of this study. The following samples 
for biomarker research are required and will be collected from all participants in this study as 
specified in Table 9.7-1. The date and time of collection will be recorded in the source documents 
and eCRFs. 
At baseline and post treatment, bone marrow aspirate (BMA) samples will be collected for 
assessing disease and response (ie, cytomorphology, cytogenetics, minimal residual disease). If 
adequate BMA is not obtainable, then a bone marrow biopsy should be completed.
Refer to the Laboratory Manual for sample collection, handling, and processing instructions.
Table 9.7-1:
Biomarker Sampling Schedule (All Participants)
Study Day of 
Sample 
Collection
(1 Cycle =
4 Weeks)a
Pharmacogenomic 
Blood Sample
Bone Marrow 
Aspirate 
(MRD)b
Biomarker Blood 
Assessment (PD)c
Biomarker Bone 
Marrow Assessment 
(NGS)d
Screening
X
X
X
Xd
Cycle 1 Day 1
X
Cycle 3 Day 1
X
X
Cycle 6 Day 1
X
Cycle 9 Day 1
X
Cycle 12 Day 1
X
Cycle 15 Day 1
X
Cycle 18 Day 1
X
Cycle 21 Day 1
X
Cycle 24 Day 1
X
Cycle 30 Day 1
X
Cycle 36 Day 1
X
EOT
X
X
Abbreviations: DNA, deoxyribonucleic acid; EOT, end of treatment; IgG, immunoglobulin G; IgM, immunoglobulin 
M; MRD, minimal residual disease; NGS, next generation sequencing; PD, pharmacodynamic.
a All sample collection for biomarker assessments will be done predose at the selected time points.
b Suggested MRD time points to parallel clinical assessment.
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c Pharmacodynamics blood samples (for DNA methylation analyses) will be collected predose at the time points 
indicated.
d Targeted sequencing of AML-specific genes (gene panel) using NGS will be conducted on screening samples.
9.8
Additional Research
This protocol will include residual sample storage for additional research. Additional and optional 
research as described below may be performed using leftover samples originally collected for 
another test required in this study or using samples collected specifically for biomarker testing. 
The research may involve genetic tests using DNA or RNA and may lead to the development of 
new diagnostic tests.

Additional research related to the study intervention and/or disease may be performed. The 
results of this additional research could help to improve the diagnosis and/or the treatment of 
this disease in the future. 

Optional research not related to the study intervention or the participant’s disease may be 
performed. The participant’s decision to participate in this optional research will not impact 
his/her ability to participate in the main study.
For All sites:
Additional research is required for all study participants, except where prohibited by IRB/ethics 
committees, 
prohibited 
by 
local 
laws 
or 
regulations, 
or 
academic/institutional 
requirements. Where one or more of these exceptions occurs, participation in the additional 
research should be encouraged but will not be a condition of overall study participation. 

If the IRB/ethics committees and site agree to the mandatory additional research retention 
and/or collection, then the study participant must agree to the mandatory additional research 
as a requirement for inclusion in the study.

If optional participation is permitted and approved, then the study participants may opt out of 
the additional research retention and/or collection.
Additional research is intended to expand the R&D capability at Bristol-Myers Squibb, and will 
support as yet undefined research aims that will advance our understanding of disease and options 
for treatment. This may also include genetic/genomic exploration aimed at exploring disease 
pathways, progression and response to treatment etc. 
Sample Collection and Storage
Residual blood and bone marrow samplings from biomarker collections (see Table 9.7-1) will also 
be retained for additional research purposes.
Samples kept for future research will be stored at the BMS Biorepository in 
, or 
an independent, BMS-approved storage vendor.
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The manager of these samples will ensure they are properly used throughout their usable life and 
will destroy the samples at the end of the scheduled storage period, no longer than fifteen (15) 
years after the end of the study or the maximum allowed by applicable law.
Transfers of samples by research sponsor to third parties will be participant to the recipient’s 
agreement to establish similar storage procedures.
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the Investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual.
Further details of sample collection and processing will be provided to the site in the procedure 
manual.
9.9
Health Economics OR Medical Resource Utilization and Health 
Economics
Health economics/medical resource utilization and health economics parameters will not be 
evaluated in this study.
10
STATISTICAL CONSIDERATIONS
10.1
Statistical Hypotheses
The primary endpoint is RFS. Based on the median RFS in the CC-486 and placebo groups of 
Study CC-486-AML-001, the expected median RFS was set at 4.8 months for placebo, and the 
expected median RFS was set at 9.5 months for CC-486. 
As the primary efficacy analysis, a Cox proportional hazards model will be used to estimate the 
corresponding hazard ratio and 95% CI for CC-486 relative to placebo. RFS curves will be 
estimated using Kaplan-Meier (KM) methods. The primary objective of this study is to estimate 
the efficacy of CC-486 as maintenance therapy by using RFS. The study does not plan to conduct 
any formal statistical hypothetical testing. For participants who do not have an RFS event, their 
RFS time will be censored at the last contact date (or “last known RFS date”). RFS will be censored 
at the date of randomization for participants who were randomized but had no response assessment.
Analysis of the primary endpoint will be conducted when the last subject completes 12 months
follow-up. However, it may need to be reconsidered depending on the occurrence status of the 
event.
10.2
Sample Size Determination
The sample size is primarily calculated as approximately 15 based on the feasibility of enrollment 
taking into consideration of the anticipated difficulty to find candidates who have achieved 
CR/CRi with conventional intensive chemotherapy in Japan. However, as many participants as 
possible will be enrolled.
With a sample size of 15 participants, assuming 2:1 ratio to adequately secure the number of 
participants in CC-486 group and to keep the number in the placebo group to a minimum, then 
approximately 10 participants will receive CC-486, and approximately 5 participants will receive 
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placebo. Based on this sample size, the probability that the point estimate of hazard ratio of CC-
486 versus placebo becomes less than 1 is 87%).
10.3
Analysis Sets
For the purposes of analysis, the following populations are defined:
Population
Description
Intent-to-treat (ITT) 
All participants who have agreed to participate in the study following 
completion of the informed consent process and registered into the IRT, 
regardless of whether they received treatment.
Modified intent-to-treat (mITT) 
All participants who have met all inclusion/exclusion criteria and experienced 
no major protocol deviations during the study, and received a minimum of 1
cycle of treatment. Participants who are registered without confirmed CR/CRi 
per central review will be excluded from the mITT population.
Safety
All participants who received at least 1 dose of study intervention.
Pharmacokinetic (PK)
All participants who received at least 1 dose of study intervention and have 
measurable plasma concentration data. All analysis of PK data will be based 
on the PK population.
Health-related Quality of Life
All participants in the ITT Population with a valid health-related quality of life 
assessment at baseline and at least 1 valid post-baseline assessment.
Abbreviations: CR, complete remission, CRi, complete remission with incomplete blood count recovery; IRT, 
Interactive Response Technology; ITT, intent-to-treat; mITT, modified intent-to-treat; PK, pharmacokinetic.
10.4
Statistical Analyses
The statistical analysis plan (SAP) will be developed and finalized before database lock and will 
describe the selection of participants to be included in the analyses and procedures for accounting 
for missing, unused, and spurious data. Below is a summary of planned statistical analyses of the 
primary and secondary endpoints.
The SAP will be finalized prior to database lock and it will include a more technical and detailed 
description of the statistical analyses described in this section. This section is a summary of the 
planned statistical analyses of the most important endpoints, including primary and secondary 
endpoints. This section describes all of the planned analyses in this protocol but some of them may 
not necessarily provide statistically meaningful estimate due to the limited sample size. In such
case, the best available summary and/or descriptive statistics will be provided.
A description of the participant population will be included in the clinical study report, including 
subgroups of age, gender, race, and other study-specific populations and demographic 
characteristics. A description of participant disposition will also be included in the clinical study 
report.
10.4.1
General Considerations
The primary and secondary estimands are described in Table 4-1.
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10.4.2
Primary Endpoint(s)
The primary efficacy endpoint of RFS is defined as the time from randomization to the date of 
documented relapse after CR or CRi per central review, or death from any cause, whichever occurs 
first.  Participants who are still alive without documented relapse after CR or CRi, or who were 
lost to follow-up without documented relapse, will be censored at the date of their last response 
assessment.  Relapse after CR or CRi is defined according the IWG AML response criteria.
The primary efficacy analysis will be conducted for the ITT Population and will compare the RFS
distributions between the two treatment groups. A Cox proportional hazards model will be used to 
estimate the corresponding hazard ratio and 95% CI for CC-486 relative to placebo. The RFS 
curves will be estimated for the primary efficacy endpoint, time to the date of documented relapse 
after CR or CRi or death from any cause, whichever occurs first, using Kaplan-Meier (KM) 
methods. Kaplan-Meier estimates for median RFS as well as the 25th and 75th percentiles and 
associated two-sided 95% CIs will be summarized for each treatment group. Plots of the KM 
survival curves will be presented for the two treatment groups.
Additionally, KM methods will be used to estimate the 1-year and 2-year RFS probabilities for 
time to death from any cause.  Estimates of the 1-year (365 days) and 2-year (730 days) survival 
probabilities and corresponding 95% confidence intervals will be presented by treatment group.  
Additional sensitivity analyses, based on the mITT Population and the ITT Population, will be 
performed using modified RFS definitions. For these analyses of RFS, participants lost to follow-
up without documented relapse will be 1) considered as having an event and 2) considered as 
having an event if they were randomized to the CC-486 treatment group and censored if they were 
randomized to the placebo treatment group.  The event/censoring time will be the date of the last 
response assessment.
To assess and compare the modified definition of AML relapse being used in this protocol as a 
criterion for discontinuation from treatment (ie, appearance of > 15% blasts in the bone marrow 
or peripheral blood) with respect to the IWG definition of relapse after CR or CRi, an exploratory 
analysis based on the mITT population will be performed for RFS using this modified definition 
of relapse. For this analysis of RFS, relapse after CR or CRi is defined as the appearance of > 15% 
blasts in the bone marrow or peripheral blood. Participants who are still alive without documented 
relapse after CR or CRi or who were lost to follow-up without documented relapse will be censored 
at the date of their last response assessment.
10.4.3
Secondary Endpoint(s)
Overall Survival
The secondary efficacy endpoint of OS is defined as the time from randomization to death from 
any cause and will be calculated using the randomization date and date of death, or date of last 
follow-up for censored participants.  All participants will be followed until dropout, death, or study 
termination.  Participants who dropout or are alive at study termination will have their OS times 
censored at the time of last contact, as appropriate. OS analysis will be conducted for the ITT 
population.
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Safety
All safety analyses will be performed on the Safety Population. Adverse events will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA).  Adverse event listings will include 
the verbatim term and the MedDRA preferred term.  Treatment-emergent adverse events (TEAEs) 
will be summarized by worst severity grade, system organ class, and preferred term.  Treatment-
emergent AEs leading to death or to discontinuation from treatment, AEs classified as NCI-
CTCAE (Version 5.0) Grade 3 or Grade 4, AEs related to IP, and SAEs will be summarized 
separately.  Time to discontinuation from the study due to AE will be summarized using KM 
methods.  Listings of all deaths and all SAEs, regardless of when they occurred, will also be 
generated.
Pharmacokinetics
The sparse concentration-time data collected in this study may be combined with a larger dataset 
to help further develop and validate the population pharmacokinetic model for azacitidine and to 
aid in the identification of covariates that influence azacitidine pharmacokinetic and/or 
pharmacodynamic measures and efficacy and safety endpoints. PK population will be used for PK 
analysis. Noncompartmental analysis will be performed using intensive sampling data.
Health-related Quality of Life
PRO endpoints include FACIT-Fatigue and the EQ-5D-5L, and analyses will include the Health-
related Quality of Life population. Summary statistics (N, mean with SD and 95% CI, median, 
first and third quartiles, minimum, maximum) for PRO measures at each assessment point will be 
provided for each treatment arm. The mean change from baseline will also be reported at each 
post-baseline assessment point. Additionally, for the EQ-5D-5L, the proportion of participants
endorsing each response option will be calculated at each time point. 
Health utility scores as assessed by the EQ-5D-5L will be derived for each subject using country-
specific weights (primary analysis will be done using UK weights). Using EQ-5D-5L scoring 
instructions, utility and VAS scores will be analyzed using the change from baseline assessment 
at each post-screening time point.
Additional details will be provided in the SAP.
10.4.4
Exploratory Endpoint(s)
Exploratory correlative analyses will be performed to assess the relationship between oral 
azacitidine concentration data and pharmacodynamic, safety, and efficacy endpoints. Appropriate 
analyses using population pharmacokinetic/pharmacodynamic approaches will be performed.
Complete cytogenetic remission (CRc) rate is defined according to the IWG AML response criteria.  
The CRc will be assessed in the subset of participants who have not achieved CRc at baseline.
For exploratory analyses, blood and bone marrow will be collected from participants from the time 
of diagnosis (if available), post induction and during maintenance therapy for molecular and/or 
cellular biomarker measurements. Results from DNA methylation and/or cytogenetics/gene 
mutation analyses will be evaluated in association with parameters of clinical outcome to 
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determine whether biomarkers predictive of OS or RFS may be identified.  The assays will be 
performed on participants in both treatment groups, placebo and CC-486. Thus a distinction 
between the prognostic and/or predictive nature of the marker(s) will be evaluated.
The relationship between genomic, molecular biomarkers and clinical outcomes will be assessed 
in participants with AML.
10.4.5
Other Safety Analysis
Not applicable.
10.4.6
Other Analyses 
Other analyses may include analyses of assessments, which are not defined as endpoints, that need 
to be prespecified and not necessarily be reported in the clinical study report, such as, but not 
limited to, immunogenicity, biomarkers, population PK, and health technology assessment-related 
endpoints.
PK and biomarker exploratory analyses will be described in the SAP finalized before database 
lock. The population PK analysis and pharmacodynamic analyses will be presented separately 
from the main clinical study report. 
10.5
Interim Analyses 
Not applicable.
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REFERENCES
1
The Japan Society of Hepatology. Guidelines for the Management of Hepatitis B Virus 
Infection. 
Guidelines 
for 
Handling 
Hepatitis 
B 
Associated 
with 
Immunosuppression/Chemotherapy. 2019 Mar. V3.1.
2
National Comprehensive Cancer Network. Clinical practice guidelines in oncology: acute 
myeloid leukemia: version 3.2021. Available from: URL:
https://www.nccn.org/professionals/physician_gls/.
3
Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2016. 
Available from: URL: https://seer.cancer.gov/csr/1975_2016/.
4
Noone AM, Howlader N, Krapcho M, et al. SEER cancer statistics review, 1975-2015. 
Available from: URL: https://seer.cancer.gov/archive/csr/1975_2015/.
5
Deschler B, de Witte T, Mertelsmann R, et al. Treatment decision-making for older patients 
with high-risk myelodysplastic syndrome or acute myeloid leukemia: problems and 
approaches. Haematologica 2006;91:1513-22.
6
Official Statistics of Japan, 2017. Available from: URL: https://www.e-stat.go.jp/stat-search/.
7
Cancer Statistics in Japan, 2015.
Available from: URL: https://ganjoho.jp/en/professional/statistics/brochure/2015_en.html.
8
Hwang SM. Classification of acute myeloid leukemia. Blood Res 2020: 55(Suppl):S1-4.
9
Leone G, Mele L, Pulsoni A, et al. The incidence of secondary leukemias. Haematologica 
1999;84:937-45.
10 Silverman L.. Myelodysplastic syndrome. Holland-Frei Can Med. 2000;5:1931-1946.
11 Löwenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med 
1999;341:1051-62.
12 Tallman MS. New strategies for the treatment of acute myeloid leukemia including antibodies 
and other novel agents. Hematology Am Soc Hematol Educ Program 2005:143-50.
13 Milligan D, Grimwade D, Cullis JO, et al; British Committee for Standards in Haematology. 
Guidelines on the management of acute myeloid leukaemia in adults. B J Haematol 
2006;135:450-74.
14 Jabbour EJ, Estey E, Kantarjian HM. Adult acute myeloid leukemia. Mayo Clin Proc 
2006;81:247-60.
15 Dombret H, Raffoux E, Gardin C. Acute myeloid leukemia in the elderly. Semin Oncol 
2008;35:430-8..
16 Burnett AK, Milligan D, Prentice AG, et al. A comparison of low-dose cytarabine and 
hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk 
myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 
2007;109:1114-24.
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17 Hofmann WK, Heil G, Zander C, et al. Intensive chemotherapy with idarubicin, cytarabine, 
etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-
risk acute myeloid leukemia. Ann Hematol 2004;83:498-503.
18 Ohtake S, Miyawaki S, Fujita H, et al. Randomized study of induction therapy comparing 
standard-dose idarubicin with high-dose daunorubicin in adult patients with previously 
untreated acute myeloid leukemia: the JALSG AML201 Study. Blood. 2011;117:2358-65.
19 Wakita A, Ohtake S, Takada S, et al. Randomized comparison of fixed-schedule versus 
response-oriented individualized induction therapy and use of ubenimex during and after 
consolidation therapy for elderly patients with acute myeloid leukemia: the JALSG GML200 
Study. Int J Hematol 2012;96:84-93.
20 National Cancer Center Japan, 2015. Available from:
URL: https://ganjoho.jp/public/index.html.
21 National Comprehensive Cancer Network. Clinical practice guidelines in oncology: acute 
myeloid leukemia: version 3.2021. Available from: 
URL: https://www.nccn.org/professionals/physician_gls/.
22 Japan Society of Hematology, 2018. Available from: URL: http://www.jshem.or.jp/guihemali/
table.html.
23 DiNardo CD, Pratz KW, Letai A, et al. Safety and preliminary efficacy of venetoclax with 
decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: 
a non-randomised, open-label, phase 1b study. Lancet Oncol 2018;19:216-28.
24 Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that 
of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a 
randomised, open-label, phase III study. Lancet Oncol 2009;10:223-32.
25 Silverman LR, McKenzie DR, Peterson BL, et al. Further analysis of trials with azacitidine in 
patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and 
Leukemia Group B. J Clin Oncol 2006;24:3895-903.
26 Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs 
conventional care regimens in older patients with newly diagnosed AML with > 30% blasts. 
Blood 2015;126:291-9.
27 Vidaza. US Prescribing Information. Celgene Corporation; 2020. Available from: URL:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050794s032lbl.pdf.
28 Onureg. US Prescribing Information. Celgene Corporation; 2020. Available from: URL: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214120s000lbl.pdf..
29 Wei AH, Döhner H, Pocock C, et al. Oral Azacitidine maintenance therapy for acute myeloid 
leukemia in first remission. N Engl J Med 2020;383:2526-37.
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30 Gore SD, Cogle CR, Skikne BS, et al. Oral azacitidine activity in patients with acute 
myelogenous leukemia. Poster session presented at: 53rd American Society of Hematology 
(ASH) Annual Meeting and Exposition; 2011 Dec 10-13; San Diego, CA, USA.
31 Laille E, Shi T, Garcia-Manero G, et al. Oral azacitidine is bioavailable and reduces DNA 
methylation at low doses in extended schedules: Phase I study results. poster session presented 
at: 11th International Symposium on Myelodysplastic Syndromes; 2011 May 18-21; 
Edinburgh, Scotland.
32 Jin M, Polis A, Hartzel J. Algorithms for minimization randomization and the implementation 
with an R package. Communications in Statistics - Simulation and Computation. May 2019. 
DOI: 10.1080/03610918.2019.1619765.
33 Cella D. The Functional Assessment of Cancer Therapy-Anemia (FACT-An) Scale: a new tool 
for the assessment of outcomes in cancer anemia and fatigue. Semin Hematol 1997;34(3 Suppl 
2):13-19.
34 Yellen SB, Cella DF, Webster K, et al. Measuring fatigue and other anemia-related symptoms 
with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain 
Symptom Manage. 1997;13:63-74.
35 Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-
level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727-36.
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12
APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
AE
adverse event
ALT
alanine aminotransferase
AML
acute myeloid leukemia
ANC
absolute neutrophil count
APL
acute promyelocytic leucemia
AST
aspartate transaminase
AxMP
auxiliary medicinal product
BM
bone marrow
BMS
Bristol-Myers Squibb
BSC
best supportive care
BUN
blood urea nitrogen
CBC
complete blood count
CI
confidence interval
CMML
chronic myelomonocytic leukemia
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CR
complete remission
CRc
complete cytogenetic remission
CRi
complete remission with incomplete blood count recovery
CRF/eCRF
case report form/electronic case report form
CTCAE
Common Terminology Criteria for Adverse Events
DNA
deoxyribonucleic acid
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
ELN
European LeukemiaNet
EOT
end of treatment
EQ-5D-5L
EuroQol 5-dimension 5-level questionnaire
ESA
Erythropoiesis-stimulating agent
FAB
French-American-British
FACIT
Functional Assessment of Chronic Illness Therapy – Fatigue 
FDA
Food and Drug Administration
G-CSF
granulocyte colony-stimulating factor
GM-CSF
granulocyte macrophage colony-stimulating factor
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
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HCV
hepatitis C virus
HIV
human immunodeficiency virus
HMA
hypomethylating agent
HR
hazard ratio
HRQoL
health-related quality-of-life
HSCT
hematopoietic stem cell transplantation
IB
Investigator’s Brochure
ICG
informed consent form
IDMC
independent data monitoring committee
IEC
Independent Ethics Committee
IgG
immunoglobulin G
IgM
immunoglobulin M
IMP
Investigational Medicinal Product
IP
investigational Product
IPSS-R
Revised International Prognostic Scoring System
IRB
Institutional Review Board
IRT
Interactive Response Technology
ITT
Intent-to-treat
IWG
International Working Group
KM
Kaplan-Meier
LDH
lactate dehydrogenase
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MDS
myelodysplastic syndrome
MedDRA
Medical Dictionary for Regulatory Affairs
mITT
modified intent-to-treat
MRD
minimal residual disease
mRFS
median relapse-free survival
NCCN
National Comprehensive Cancer Network
NCI-CTCAE
National Cancer Institute-Common Terminology Criteria for Adverse 
Events
NGS
next generation sequencing
OS
overall survival
PCR
polymerase chain reaction
PD
pharmacodynamic
PK
pharmacokinetic
PR
partial remission
PS
performance status
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QD
once daily
RA
refractory anemia
RAEB
refractory anemia with excess blasts
RAEB-T
refractory anemia with excess blasts in transformation
RARS
refractory anemia with ringed sideroblasts
RBC
red blood cell
RFS
relapse-free survival
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SC
subcutaneous
SCT
stem cell transplantation
SD
standard deviation
SUSAR
suspected, unexpected serious adverse reaction
TEAE
treatment-emergent adverse event
TSA
thrombopoiesis-stimulating agent
ULN
upper limit of normal
US
United States
VAS
visual analog scale
WBC
white blood cell 
WHO
World Health Organization
WOCBP
women of childbearing potential
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
The terms “participant” and “subject” refer to a person who has consented to participate in the 
clinical research study. Typically, the term “participant” is used in the protocol and the term 
“subject” is used in the Case Report Form (CRF).
Regulatory and Ethical Considerations
This study will be conducted in accordance with:

Consensus ethical principles derived from international guidelines, including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
International Ethical Guidelines

Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP)
Guidelines

Applicable laws, regulations, and requirements
The study will be conducted in compliance with the protocol. The protocol,
any 
revisions/amendments,
and the participant
informed consent form (ICF) will receive 
approval/favorable 
opinion 
by 
Institutional 
Review 
Board/Independent 
Ethics 
Committee (IRB/IEC), and regulatory authorities according to applicable regulations prior to 
initiation of the study.
All potential serious breaches must be reported to the Sponsor or designee immediately. A 
potential serious breach is defined as a Quality Issue (eg, protocol deviation) that is likely to affect, 
to a significant degree, one or more of the following: (1) the rights, physical safety or mental 
integrity of one or more participants; (2) the scientific value of the clinical trial (eg, reliability and 
robustness of generated data). Items (1) or (2) can be associated with either GCP regulation(s) or 
trial protocol(s).
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
Institutional Review Board/Independent Ethics Committee
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, Investigator’s Brochure, product labeling information, ICF, 
participant recruitment materials (eg, advertisements), and any other written information to be 
provided to participants.
The investigator, Sponsor, or designee should provide the IRB/IEC with reports, updates, and other 
information (eg, expedited safety reports, amendments, administrative letters) annually, or more 
frequently, in accordance with regulatory requirements or institution procedures.
The investigator is responsible for providing oversight of the conduct of the study at the site and 
adherence to requirements of the following where applicable:
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
ICH guidelines, 

United States Code of Federal Regulations, Title 21, Part 50 (21CFR50)

European Union Directive 2001/20/EC; or

European Regulation 536/2014 for clinical studies (if applicable), 

European Medical Device Regulation 2017/745 for clinical device research (if applicable),

the IRB/IEC

and all other applicable local regulations.
Compliance with the Protocol and Protocol Revisions
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and, if 
applicable, also by the local Health Authority), except where necessary to eliminate an immediate 
hazard(s) to study participants. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s), the deviation or change will be submitted as soon 
as possible to:

IRB/IEC

Regulatory authority(ies), if applicable by local regulations (per national requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and, if applicable, also by the local Health Authority, must be sent to Bristol-Myers 
Squibb (BMS).
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the ICF must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from participants 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new participants prior to enrollment.
Financial Disclosure
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information, in accordance with regulations, to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate Health Authorities. Investigators 
are responsible for providing information on financial interests during the course of the study and 
for 1 year after completion of the study.
Informed Consent Process
Investigators must ensure that participants are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which they volunteer to 
participate. 
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The Sponsor or designee will provide the investigator with an appropriate sample ICF, which will 
include all elements required by the ICH GCP, and applicable regulatory requirements. The sample 
ICF will adhere to the ethical principles that have their origin in the Declaration of Helsinki.
The investigator or his/her representative must:

Obtain IRB/IEC written approval/favorable opinion of the written ICF and any other 
information to be provided to the participant prior to the beginning of the study and after any 
revisions are completed for new information.

Provide a copy of the ICF and written information about the study in the language in which 
the participant is proficient prior to clinical study participation. The language must be 
nontechnical and easily understood. 

Explain the nature of the study to the participant and answer all questions regarding the study.

Inform participant that his/her participation is voluntary. Participant will be required to sign a 
statement of informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, 
where applicable, and the IRB/IEC or study center.

Allow time necessary for participant to inquire about the details of the study.
Obtain an ICF signed and personally dated by participant and by the person who conducted the 
informed consent discussion. 

Include a statement in participant’s medical record that written informed consent was obtained 
before participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF.

Re-consent participant to the most current version of the ICF(s) during his/her participation in 
the study, as applicable.
Revise the ICF whenever important new information becomes available that is relevant to the 
participant’s consent. The investigator, or a person designated by the investigator, should fully 
inform the participant of all pertinent aspects of the study and of any new information relevant to 
the participant’s willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify participants must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the participant’s signed 
ICF, and, in the US, the participant’s signed HIPAA Authorization.
The ICF must also include a statement that BMS and local and foreign regulatory authorities have 
direct access to participant records. 
In situations where consent cannot be given by participants, their legally acceptable representatives 
(as per country regulation) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the participant volunteers to participate. 
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If informed consent is initially given by a participant’s legally acceptable representative or legal 
guardian and the participant subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the participant.
The rights, safety, and well-being of the study participants are the most important considerations 
and should prevail over interests of science and society.
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the electronic CRF (eCRF) that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be explained. 

The investigator may need to request previous medical records or transfer records, depending 
on the study. Also, current medical records must be available.

Definitions of what constitutes source data can be found in the examples; hospital records; 
clinic and office charts; laboratory notes; memoranda; participant’s diaries or evaluation 
checklists; dispensing records; recorded data from automated instruments; copies or 
transcriptions certified after verification as being accurate copies; microfiche; x-ray film and 
reports; and records kept at the pharmacy, and the laboratories, as well as copies of eCRFs or 
CD-ROM.
The investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original, and attributable, whether the data are handwritten on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical records/electronic health 
records, adverse event (AE) tracking/reporting, protocol-required assessments, and/or drug 
accountability records.
When paper records from such systems are used in place of an electronic format to perform 
regulated activities, such paper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original. 
Study Intervention Records
Records must be made available for review at the request of BMS/designee or a Health Authority.
Records for study intervention (whether supplied by BMS, its vendors, or the site) must 
substantiate study intervention integrity and traceability from receipt, preparation, administration, 
and through destruction or return. Records must be made available for review at the request of 
BMS/designee or a Health Authority.
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If
Then
Supplied by BMS (or its vendors):
Records or logs must comply with applicable 
regulations and guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number

amount dispensed to and returned by each 
participant, including unique participant
identifiers

amount transferred to another area/site for 
dispensing or storage

nonstudy disposition (eg, lost, wasted) 

amount destroyed at study site, if applicable

amount returned to BMS

retain samples for 
bioavailability/bioequivalence/biocomparability, 
if applicable 

dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the Delegation 
of Authority Form
Sourced by site and not supplied by BMS 
or its vendors (examples include IP 
sourced from the sites’
stock or 
commercial supply or a specialty 
pharmacy)
The investigator or designee accepts responsibility 
for documenting traceability and study treatment
integrity in accordance with requirements applicable 
under 
law 
and 
the 
standard
operating 
procedures/standards of the sourcing pharmacy
BMS or its designee will provide forms to facilitate inventory control if the investigational site 
does not have an established system that meets these requirements.
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents, or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the Sponsor or designee electronic data capture (EDC) tool, eCRFs will be prepared 
for all data collection fields except for fields specific to SAEs and pregnancy, which will be 
reported on the electronic SAE form and Pregnancy Surveillance Form, respectively. If the 
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electronic SAE form is not available, a paper SAE form can be used. Spaces may be left blank 
only in those circumstances permitted by study-specific CRF completion guidelines provided by 
the Sponsor or designee.
The confidentiality of records that could identify participants must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF and SAE/pregnancy CRFs must be promptly reviewed, signed, and dated by 
the investigator or qualified physician who is a sub-investigator and who is delegated this task on 
the Delegation of Authority Form. Sub-investigators in Japan may not be delegated the CRF 
approval task. For eCRFs, review and approval/signature is completed electronically through the 
BMS EDC tool. The investigator must retain a copy of the CRFs, including records of the changes 
and corrections.
Each individual electronically signed eCRF must meet Sponsor or designee training requirements 
and must only access the BMS EDC tool using the unique user account provided by the Sponsor 
or designee. User accounts are not to be shared or reassigned to other individuals.
Monitoring
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site, they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable.
In addition, the study may be evaluated by the Sponsor or designee internal auditors and 
government inspectors who must be allowed access to CRFs, source documents, other study files, 
and study facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities 
and promptly forward copies of inspection reports to the Sponsor or designee.
Records Retention
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or its designee, whichever is longer. 
The investigator (or head of the study site in Japan) must contact BMS prior to destroying any 
records associated with the study.
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BMS or its designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed-upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or its designee. 
Return of Study Treatment
For this study, study treatments (those supplied by BMS or a vendor or sourced by the 
investigator), such as partially used study treatment containers, vials, and syringes, may be 
destroyed on site. 
If
Then
Study treatments supplied by BMS (including 
its vendors)
Any unused study interventions supplied by 
BMS can only be destroyed after being 
inspected and reconciled by the responsible 
Study 
Monitor,
unless 
study 
treatment
containers must be immediately destroyed as 
required for safety, or to meet local regulations 
(eg, cytotoxics or biologics).
Partially used study interventions and/or 
empty containers may be destroyed after 
proper reconciliation and documentation. But 
unused IMP must be reconciled by site 
monitor/Clinical Research Associate prior to 
destruction.
If study treatments will be returned, the return 
will be arranged by the responsible Study 
Monitor.
Study treatments sourced by site, not supplied 
by BMS (or its vendors; eg, study treatments 
sourced from the site’s stock or commercial 
supply or a specialty pharmacy)
It 
is 
the 
investigator’s 
or 
designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
It is the investigator’s or designee’s responsibility to arrange for disposal of study interventions, 
provided that procedures for proper disposal have been established according to applicable federal, 
state, local, and institutional guidelines and procedures, and provided that appropriate records of 
disposal are kept. The following minimal standards must be met:

On-site disposal practices must not expose humans to risks from the drug.

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.
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
Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s standard operating procedures and a copy provided to BMS upon request.

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal (eg, incinerator, licensed sanitary landfill, or licensed waste-disposal 
vendor) must be documented.

Accountability and disposal records are complete, up-to-date, and available for the Study 
Monitor to review throughout the clinical trial period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers.
If conditions for destruction cannot be met, the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of non-study 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee.
Study and Site Start and Closure
The Sponsor/designee reserves the right to close the study site or to terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies have 
been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the Sponsor or investigator may include, but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local Health Authorities, the Sponsor’s procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Dissemination of Clinical Study Data
In order to benefit potential study participants, patients, healthcare providers and researchers, and 
to help BMS honor its commitments to study participants, BMS will make information about 
clinical research studies and a summary of their results available to the public as per regulatory 
and BMS requirements. BMS will post study information on local, national or regional databases 
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in compliance with national and international standards for disclosure. BMS may also voluntarily 
disclose information to applicable databases.
Clinical Study Report
A Signatory Investigator must be selected to sign the Clinical Study Report (CSR). 
For each CSR related to this protocol, the following criteria will be used to select the Signatory 
Investigator:

Participant recruitment (eg, among the top quartile of enrollers)
Scientific Publications
The data collected during this study are confidential and proprietary to the Sponsor or designee. 
Any publications or abstracts arising from this study must adhere to the publication requirements 
set forth in the Clinical Trial Agreement (CTAg) governing [study site or investigator] 
participation in the study. These requirements include, but are not limited to, submitting proposed 
publications to the Sponsor or designee at the earliest practicable time prior to submission or 
presentation and otherwise within the time period set forth in the CTAg.
Scientific publications (such as abstracts, congress podium presentations and posters, and 
manuscripts) of the study results will be a collaborative effort between the study Sponsor and the 
external authors. No public presentation or publication of any interim results may be made by any 
Principal Investigator, sub-investigator, or any other member of the study staff without the prior 
written consent of the Sponsor.
Authorship of publications at BMS is aligned with the criteria of the International Committee of 
Medical Journal Editors (ICMJE, www.icmje.org). Authorship selection is based upon significant 
contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for 
authorship:
1) Substantial intellectual contribution to the conception or design of the work; or the acquisition 
of data (ie, evaluable participants with quality data), analysis, or interpretation of data for the 
work (eg, problem solving, advice, evaluation, insights and conclusion); AND
2) Drafting the work or revising it critically for important intellectual content; AND
3) Final approval of the version to be published; AND
4) Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Those who make the most significant contributions, as defined above, will be considered by BMS 
for authorship of the primary publication. Sub-investigators will generally not be considered for 
authorship in the primary publication. Geographic representation will also be considered.
Authors will be listed by order of significant contributions (highest to lowest), with the exception 
of the last author. Authors in first and last position have provided the most significant contributions 
to the work. 
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For secondary analyses and related publications, author list and author order may vary from 
primary to reflect additional contributions.
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APPENDIX 3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING
Adverse Events
Adverse Event Definition:
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a 
pre-existing medical condition in a clinical investigation participant administered study 
treatment that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study treatment, whether or 
not considered related to the study treatment.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, electrocardiograms, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis.

Exacerbation of a chronic or intermittent pre-existing condition, including either an increase 
in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration, even though 
it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose, as a verbatim term (as reported by the investigator), 
should not be reported as an AE/serious adverse event (SAE) unless it is an intentional 
overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae and should specify “intentional overdose” as the verbatim 
term.
Events NOT Meeting the AE Definition

Medical or surgical procedure (eg, endoscopy, appendectomy); the condition that leads to 
the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE, even if serious conditions 
are met.
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Serious Adverse Events
A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any 
dose:
Results in death.
Is life-threatening (defined as an event in which the participant was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if it were 
more severe).
Requires inpatient hospitalization or causes prolongation of existing hospitalization (see NOTE 
below).
NOTE: 
The following hospitalizations are not considered SAEs in Bristol-Myers Squibb (BMS) clinical 
studies: 

A visit to the emergency room or other hospital department < 24 hours that does not result 
in admission (unless considered an important medical or life-threatening event).

Elective surgery, planned prior to signing consent.

Admissions as per protocol for a planned medical/surgical procedure.

Routine health assessment requiring admission for baseline/trending of health 
status (eg, routine colonoscopy).

Medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases.

Admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (eg, lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason).

Admission for administration of anticancer therapy in the absence of any other 
SAEs (applies to oncology protocols).
Results in persistent or significant disability/incapacity.
Is a congenital anomaly/birth defect.
Is an important medical event (defined as a medical event[s] that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the participant or may require intervention [eg, medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above). Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm and blood dyscrasias or convulsions that do not result in 
hospitalization. Potential drug-induced liver injury (DILI) is also considered an important 
medical event. (See Section 9.2.7 for the definition of potential DILI.) 
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Pregnancy and DILI must follow the same transmission timing and processes to BMS as used for 
SAEs. (See Section 9.2.5 for reporting pregnancies.)
Evaluating AEs and SAEs
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration,
will be considered and investigated.

The investigator will also consult the Investigator’s Brochure and/or product information for 
marketed products in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important that 
the investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to the Sponsor.

The investigator may change his/her opinion of causality in light of follow-up information 
and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.

Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and grade the intensity of AEs and SAEs based upon the symptoms according to the 
current active minor version of the Common Terminology Criteria for Adverse Events (CTCAE, 
Version 5.0) 
Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL).
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self care ADL.
Grade 4 Life-threatening consequences; urgent intervention indicated.
Grade 5 Death related to AE.
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Follow-up of AEs and SAEs
If only limited information is initially available, follow-up reports are required. 
(Note: Follow-up SAE reports must include the same investigator term[s] initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study treatment or if new 
information becomes available, the SAE report must be updated and submitted within 24 hours 
to BMS (or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
Reporting of SAEs to Sponsor or Designee

SAEs, whether related or not related to study treatment, and pregnancies must be reported 
to BMS (or designee) immediately within 24 hours of awareness of the event.

SAEs must be recorded on the SAE Report Form.

The required method for SAE data reporting is through the electronic case report 
form (eCRF).

The paper SAE Report Form is intended only as a back-up option when the electronic 
data capture system is unavailable/not functioning for transmission of the eCRF to BMS 
(or designee).
In this case, the paper form is transmitted via email or confirmed facsimile 
transmission.
When paper forms are used, the original paper forms are to remain on site.

Pregnancies must be recorded on paper Pregnancy Surveillance Forms and transmitted via 
email or confirmed facsimile transmission.
SAE Email Address: worldwide.safety@BMS.com
SAE Facsimile Number: Will be provided by local site monitor.
SAE Telephone Contact (required for SAE and pregnancy reporting): Will be provided by local 
site monitor.
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APPENDIX 4
CONTRACEPTION REQUIREMENTS
Refer to Protocol Section 6.1, Inclusion Criteria, for contraception time frames.
Methods of Contraception
Local laws and regulations may require use of alternative and/or additional contraception methods.
Highly Effective Contraceptive Methods That Are User Dependent
Failure rate of < 1% per year when used consistently and correctlya
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation and/or implantation (This method of contraception can only be used by
Women of childbearing potential (WOCBP) participants in studies where hormonal
contraception is permitted by the study protocol.)b

Oral (birth control pills)

Intravaginal (rings)

Transdermal
Combined (estrogen and progestogen-containing) hormonal contraception must begin at least 
28 days prior to initiation of study therapy.
Progestogen-only hormonal contraception associated with inhibition of ovulation. (This method of contraception can 
only be used by WOCBP participants in studies where hormonal contraception is permitted by the study protocol.)b
Oral
Injectable
Progestogen-only hormonal contraception must begin at least 28 days prior to initiation of study therapy.
Highly Effective Methods That Are User Independent
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation
and/or implantation. (This method of contraception can only be used by WOCBP participants in 
studies where hormonal contraception is permitted by the study protocol.)b
Intrauterine device.
Intrauterine hormone-releasing system (IUS). (This method of contraception can only be used by 
WOCBP participants in studies where hormonal contraception is permitted by the study 
protocol.)b, c
Bilateral tubal occlusion.
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Vasectomized partner
Male participants will be required to always use a latex or other synthetic condom during any
sexual activity (eg, vaginal, anal, oral) with WOCBP, even if the participants have undergone a
successful vasectomy or if their partner is already pregnant or breastfeeding.
Sexual abstinence

Sexual abstinence is considered a highly effective method only if defined as absolutely 
(100% of time) refraining from heterosexual intercourse during the entire period of risk 
associated with the study treatment. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study. For abstinence to be considered an 
acceptable method of contraception, it must be the preferred and usual lifestyle of the 
study participant.
Continuous abstinence must begin at least 28 days prior to initiation of study therapy.
It is not necessary to use any other method of contraception when complete abstinence is 
elected.
WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in the protocol Schedule of Activities (Section 2).
Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants chooses to forego complete abstinence.
Periodic abstinence (including but not limited to calendar, symptothermal, post-ovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea 
method (LAM) are not acceptable methods of contraception for this study.
NOTES:
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants participating in clinical studies.
b Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the 
efficacy of the contraceptive method. Hormonal contraception is permissible only when there is sufficient 
evidence that the investigational product and other study medications will not alter hormonal exposures such
that contraception would be ineffective or result in increased exposures that could be potentially hazardous. In
this case, alternative methods of contraception should be utilized.
c Intrauterine hormone releasing systems are acceptable methods of contraception in the absence of definitive drug 
interaction studies when hormone exposures from intrauterine devices do not alter contraception effectiveness
Collection of Pregnancy Information
Guidance for collection of pregnancy information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and APPENDIX 3.
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APPENDIX 5
ECOG PERFORMANCE STATUS CRITERIA
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Score
Description
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, eg, light housework, 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, Horton J, Davis TE, McFadden ET, et al. Toxicity and 
response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55.
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APPENDIX 6
INTERNATIONAL WORKING GROUP AML RESPONSE CRITERIA
Hematologic Response According to IWG Criteria for AML
Category
Definition
Morphologic Complete Remission (CR)
The following conditions should be met:

ANC > 1,000/μL;

Platelet count ≥ 100,000/μL; 

The bone marrow should contain less than 5% blast cells; 

Auer rods should not be detectable;

No evidence of extramedullary disease;

Independent of transfusions.
Morphologic Complete Remission with 
Incomplete Blood Count Recovery (CRi)
Defined as a morphologic complete remission but the ANC count may be            
< 1,000/μL or the platelet count may be < 100,000/μL.
Cytogenetic Complete Remission (CRc)
Defined as morphologic complete remission with a reversion to a normal 
karyotype.
Relapse Free Survival
Defined for patients who achieve CR/CRi, and is measured from the date of 
attaining leukemia free state until the date of AML relapse or death from any 
cause, whichever occurs first.
Disease Relapse
Relapse after CR/CRi is defined as reappearance of leukemic blasts in the 
peripheral blood or ≥ 5% blasts in the bone marrow not attributable to any 
other cause (eg, bone marrow regeneration after consolidation therapy).  In the 
setting of recent treatment, if there are no circulating blasts and the bone 
marrow contains 5% to 20% blasts, a repeat bone marrow performed at least a 
week later is necessary to distinguish relapse from regeneration.
Source: Cheson BD, Bennett JM, Kopecky KJ, et al.  Revised Recommendations of the International Working Group for 
Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute 
Myeloid Leukemia. J Clin Oncol 2003;21:4642-9.
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APPENDIX 7
RECOMMENDATIONS FOR MANAGEMENT OF TREATMENT-
INDUCED DIARRHEA
The following published guidelines (Benson, 2004) were modified in order to be consistent with the 
clinical study protocol.
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APPENDIX 8
FACIT-FATIGUE SCALE (VERSION 4)
Below is a list of statements that other people with your illness have said are important. 
Please circle or mark one number per line to indicate your response as it applies to the past 
7 days.
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APPENDIX 9
EQ-5D-5L HEALTH QUESTIONNAIRES
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APPENDIX 10
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
Overall Rationale for Protocol Amendment 01, 25-July-2022
The main objective of Protocol Amendment 01 is to add an Eastern Cooperative Oncology Group 
(ECOG) performance status as a new inclusion criterion. Additionally, updates were made to 
clarify the assessments to be performed at appropriate time points, improve alignment across 
protocol sections and establish consistency, and update contact information.
Other revisions, including to sections of the Protocol Summary, have been made to align the 
protocol with respect to these changes.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Title page
Updated contact information for 
the Clinical Trial Physician and 
Clinical Scientist as well as 
Bristol Myers Squibb KK 
headquarters relocation.
Sponsor contract information was 
updated.
Protocol 
Summary
Section 3.1: 
Study 
Rationale
Section 3.2: 
Background
The dose of daunorubicin for 
common induction regimen was 
aligned with the National 
Comprehensive Cancer Network
(NCCN) guideline.
The dose of daunorubicin was modified 
to align with the NCCN guideline.
Table 2-1: 
Screening 
Procedural 
Outline 
(CA055005)
ECOG Performance Status was 
updated to perform the evaluation 
at randomization or Cycle 1 Day 1 
(C1D1).
Table was updated to perform the 
assessment at the appropriate time point.
Table 2-3: 
End-of-
treatment and 
Follow-up 
Procedural 
Outline 
(CA055005)
Concomitant Medications, 
Therapy and Procedures was 
updated to include assessments at 
End of Treatment/Early 
Termination and Follow-up.
Table was updated to perform the 
assessment at the appropriate time point.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Section 6.1 
Inclusion 
Criteria
Modified inclusion criterion 2) b);
Must have achieved first complete 
remission (CR)/complete 
remission with incomplete blood 
count recovery (CRi) status within 
4 months (± 7 days) prior to 
“randomization”, as evidenced by 
the following.
Added a new inclusion criterion 
for ECOG performance status.
The 
4 
month 
duration 
prior 
to 
randomization for first CR/CRi status 
was aligned with the protocol.
Inclusion criterion was added to define 
the ECOG performance status.
Section 7.3 
Blinding
Removed the description of 
randomization schedules.
This process is not applied to this study.
Section 9.5 
Pharmacokine
tics
Modified the descriptions and 
added the definition of 
pharmacokinetic parameters.
The descriptions were modified based 
on BMS formatting.
Table 9.7-1: 
Biomarker 
Sampling 
Schedule (All 
Participants)
Removed Biomarker Bone 
Marrow Assessment (NGS) at 
Diagnosis.
Removed Bone Marrow Aspirate 
(MRD) at Cycle 1 Day 1.
No sample collection for NGS or MRD 
occurs at Diagnosis and Cycle 1 Day 1.
Appendix 3 
ADVERSE 
EVENTS 
AND 
SERIOUS 
ADVERSE 
EVENTS:
DEFINITION
S AND 
PROCEDURE
S FOR 
RECORDING
, 
EVALUATIN
G, FOLLOW-
UP, AND 
REPORTING
Assessment of Intensity was 
updated to National Cancer 
Institute-Common Terminology 
Criteria for Adverse Events 
Version 5.0 grading.
The severity was aligned with Section 
7.4.1: Dose Modifications for Toxicity.
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