Clinical trial NCT02873338
Conditions: Acute Myeloid Leukemia
Sponsor: Chimerix
Start date: 2016-08-01; Completion date: 2019-06-01
Enrollment: 75 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This was an exploratory Phase 2, open label, randomized, multicenter, parallel group study to determine whether there was evidence that the addition of dociparstat (CX-01) at 2 different does levels to standard induction therapy (cytarabine+idarubicin, "7+3") and consolidation therapy had an additive therapeutic effect for subjects newly diagnosed with acute myeloid leukemia (AML) when compared with subjects receiving standard induction chemotherapy alone.

Detailed description:
The primary efficacy endpoint was to assess whether dociparstat in conjunction with standard induction therapy for AML increased the complete remission rate based on the International Working Group AML response criteria.

A total of 75 subjects were to be randomized in a 1:1:1 ratio to 1 of the following treatment groups:

* Group 1: cytarabine + idarubicin
* Group 2: cytarabine + idarubicin + dociparstat 0.125 mg/kg/hr
* Group 3: cytarabine + idarubicin + dociparstat 0.25 mg/kg/hr

Subjects received up to 2 induction cycles and up to 2 consolidation cycles and participated in the study for up to 18 months. Clinical laboratory tests were conducted routinely, and bone marrow aspirates and biopsies were performed during the induction cycles. Safety was monitored through adverse events and clinical laboratory results.

Arms: arm 1: Induction:

* Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, and 3)
* Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 7)

Re-induction:

* Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1 and 2)
* Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 5)

Consolidation:

• Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, and 5) arm 2: Induction:

* Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/hr continuous 24-hour intravenous (IV) infusion (Days 1 to 7)
* Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, and 3)
* Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 7)

Re-induction:

* Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/hr continuous 24-hour IV infusion (Days 1 to 5)
* Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1 and 2)
* Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 5)

Consolidation:

* Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/hr continuous 24-hour IV infusion on (Days 1 to 5; total 120 hours)
* Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, and 5) arm 3: Induction:

* Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/hr continuous 24-hour intravenous (IV) infusion (Days 1 to 7)
* Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, and 3)
* Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 7)

Re-induction:

* Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/hr continuous 24-hour IV infusion (Days 1 to 5)
* Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1 and 2)
* Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 5)

Consolidation:

* Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/hr continuous 24-hour IV infusion (Days 1 to 5; total 120 hours)
* Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, and 5)
Interventions: intervention 1: Dociparstat sodium intervention 2: Idarubicin intervention 3: Cytarabine
Intervention descriptions: intervention 1: Subjects received 4 mg/kg dociparstat intravenous (IV) bolus followed by doses of 0.125 or 0.25 mg/kg/hr dociparstat given on Days 1 through 7 with standard induction therapy, on Days 1 through 5 or 7 with standard re-induction therapy, and on Days 1, 3, and 5 with standard consolidation therapy. intervention 2: Subjects received 12 mg/m2/day idarubicin by slow (10 to 15 minutes) intravenous (IV) injection daily on Days 1, 2 and 3 of induction therapy, and on Days 1 and 2 of re-induction therapy. intervention 3: Subjects received 100 mg/m2/day cytarabine by continuous intravenous (IV) infusion on Days 1 through 7 of induction therapy and on Days 1 through 5 of re-induction therapy. During consolidation therapy, subjected received 1.0 g/m2 cytarabine IV infusion given over 3 hours every 12 hours on Days 1, 3, and 5.

Protocol documents:
Prot_000.pdf: 
Protocol Title: A Randomized, Phase II Study of CX-01 Combined With Standard 
Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia 
 
Protocol Number: CNTX-CX-01-2015-AML-1 (NCT02873338) 
 
Protocol Date: 04 February 2016 
Amendment 1: 16 September 2016 
Amendment 2: 13 January 2017 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 1 of 89 
CONFIDENTIAL 
 
 
Clinical Study Protocol 
 
Protocol Title: 
A Randomized, Phase II Study of CX-01 Combined With Standard 
Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia 
 
 
 
IND Number: 
118 960 
Product: 
CX-01 (2-O, 3-O desulfated heparin; ODSH) 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Phase: 
II 
 
 
Prepared for: 
 
 
Cantex Pharmaceuticals, Inc. 
1792 Bell Tower Lane 
Weston, Florida 33326 
 
 
By: 
Covance Inc. 
210 Carnegie Center 
Princeton, New Jersey 08540-6233 
 
 
 
Date of Protocol: 
FEBRUARY 04, 2016 
Final Protocol incorporating Amendment 1: SEPTEMBER 16, 2016 
Final Protocol incorporating Amendment 2: JANUARY 13, 2017 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 
Information described herein is confidential and may be disclosed 
only with the express written permission of Cantex Pharmaceuticals, Inc. 
This study will be performed in compliance with Good Clinical Practices. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 2 of 89 
CONFIDENTIAL 
 
 
 
KEY STUDY PERSONNEL 
 
 
Sponsor’s Medical Monitor: 
Stephen Marcus, M.D. 
Chief Executive Officer 
Cantex Pharmaceuticals, Inc. 
1792 Bell Tower Lane 
Weston, Florida 33326 
Office: 1-(954)-315-3660 
Cell: 1-(954)-540-1124 
Email: smarcus@cantex.com 
 
Contract Research 
Covance Inc. 
Organization (CRO): 
210 Carnegie Center 
Princeton, New Jersey 08540-6233 
Phone: 1-(609)-452-8550 
 
Covance Inc. Medical Monitor: 
Naftali Bechar, M.D. 
Covance Inc. 
Phone: 1-(609)-452-4351 
Email: naftali.bechar@covance.com 
 
SERIOUS ADVERSE EVENT 
REPORTING 
Covance Pharmacovigilance & Drug Safety 
Services (PV&DSS) 
Phone: 1-(888)-887-8097 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 3 of 89 
CONFIDENTIAL 
 
 
 
SYNOPSIS 
 
Study Number: 
CNTX-CX-01-2015-AML-1 
Title of Study: 
A Randomized, Phase II Study of CX-01 Combined With Standard Induction 
Therapy for Newly Diagnosed Acute Myeloid Leukemia 
Indication: 
Newly diagnosed acute myeloid leukemia (AML) 
Number of 
Investigators and 
Study Centers: 
The study will be conducted at approximately 25 sites in the United States. 
Development Phase: 
Phase II 
Objectives: 
Primary objectives 
The primary objectives are: 
• 
To assess whether 2-O, 3-O desulfated heparin (CX-01), administered 
at any or all studied dose levels in conjunction with standard induction 
therapy for AML increases the morphologic complete remission (CR) 
rate based on International Working Group (IWG) criteria 
• 
To assess the safety and tolerability of CX-01, administered at two 
studied dose levels in conjunction with standard induction therapy for 
AML. 
Secondary objectives 
The secondary efficacy objectives are: 
To assess whether CX-01, administered at any or all studied dose levels in 
conjunction with standard induction and consolidation therapy for AML 
improves: 
• 
Event-free survival (EFS) 
• 
Leukemia-free survival (LFS) 
• 
Overall survival (OS) 
• 
Composite CR rate: incidence of CR + CRi, which is CR without 
recovery of neutrophils and/or platelets (ANC may be <1000 μL and/or 
platelet count <100,000/μL). 
• 
Duration of morphologic CR 
• 
30-day mortality (in the induction cycle) 
• 
60-day mortality (in the induction cycle) 
• 
90-day mortality (in the induction cycle) 
• 
Neutrophil recovery 
• 
Platelet recovery. 
Study Population: 
Newly diagnosed, treatment-naïve patients with de novo or secondary AML 
60 years of age or older. 
Methodology/ 
Study Design: 
This is an exploratory phase II, open-label, randomized, multicenter, parallel 
group trial to determine whether there is evidence that the addition of either or 
both different dose levels of CX-01 to standard induction and consolidation 
chemotherapy has an additive therapeutic effect in newly diagnosed AML 
patients when compared to patients receiving standard induction chemotherapy 
alone. 
Patients will be randomized in a 1:1:1 ratio to receive standard induction and 
consolidation chemotherapy plus lower or higher dose CX-01 or standard 
induction and consolidation chemotherapy alone. 
During long term follow-up, relapse and OS data will be collected every 
3 months until death or until the end of study. The end of study will occur 
approximately 18 months after the last patient is randomized. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 4 of 89 
CONFIDENTIAL 
 
 
 
A Data and Safety Monitoring Committee will meet periodically to review the 
safety of the study. 
Adverse events (AEs) will be collected from time of informed consent and 
continue until 30 days after last study treatment is administered. Longer follow- 
up and collection of AEs may be required for patients who do not have an 
absolute neutrophil count (ANC) recovery by Day 42 (i.e. until the recovery or 
until the reason for no recovery is diagnosed) after the last induction or 
consolidation cycle. 
Number of Patients 
(planned and 
analyzed): 
Approximately 75 patients 
Study Medications: 
Group 1: Idarubicin + Cytarabine, OR 
Group 2: Idarubicin + Cytarabine + plus lower dose CX-01 
(0.125 mg/kg/hour), OR 
Group 3: Idarubicin + Cytarabine + plus higher dose CX-01 (0.25 mg/kg/hour) 
Dose regimen: 
For induction therapy, all patients will receive standard idarubicin + cytarabine 
chemotherapy. Patients randomized to Groups 2, and 3 will also receive CX-01. 
CX01 will be continually infused while idarubicin will be administered per 
institutional standards. Patient will be randomized to one of the following 
treatment groups: 
Induction therapy: 
Group 1: Idarubicin + Cytarabine 
• 
Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) 
injection/infusion daily on Days 1, 2, and 3 
• 
Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on 
Days 1-7. 
Group 2: Idarubicin + Cytarabine + plus lower dose CX-01 
• 
CX-01 given as a 4 mg/kg initial bolus on Day 1 only, 30 minutes after 
completion of administration of the first dose of idarubicin, followed 
by CX-01 0.125 mg/kg/hour as a continuous 24-hour IV infusion on 
Days 1-7 
• 
Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV 
injection/infusion daily on Days 1, 2, and 3 
• 
Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on 
Days 1-7. 
Group 3: Idarubicin + Cytarabine + plus higher dose CX-01 
• 
CX-01 given as a 4 mg/kg initial bolus on Day 1 only, 30 minutes after 
completion of administration of the first dose of idarubicin, followed 
by CX-01 0.25 mg/kg/hour as a continuous 24-hour IV infusion on 
Days 1-7 
• 
Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV 
injection/infusion daily on Days 1, 2, and 3 
• 
Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on 
Days 1-7. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 5 of 89 
CONFIDENTIAL 
 
 
 
Re-induction therapy 
Patients who do not achieve leukemia-free state (<5% bone marrow blasts) on 
bone marrow aspirate performed between Days 14-21 may receive a 
re-induction cycle with the same regimen (“7 + 3” ± CX-01) as outlined above. 
If, in the Investigator’s opinion, the patient is not fit to receive full re-induction 
cycle of “7 + 3” ± CX-01, at the Investigator’s discretion the patient may 
receive “5 + 2” ± CX-01 which is 5 days of cytarabine and 2 days of idarubicin 
± CX-01 as outlined below: 
Group 1: Idarubicin + Cytarabine 
• 
Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV 
injection/infusion daily on Days 1and 2 
• 
Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on 
Days 1-5. 
Group 2: Idarubicin + Cytarabine + plus lower dose CX-01 
• 
CX-01 given as a 4 mg/kg initial bolus on Day 1, 30 minutes after 
completion of administration of the first dose of idarubicin, followed 
by CX-01 0.125 mg/kg/hour as a continuous 24-hour IV infusion on 
Days 1-5 
• 
Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV 
injection/infusion daily on Days 1and 2 
• 
Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on 
Days 1-5. 
Group 3: Idarubicin + Cytarabine + plus higher dose CX-01 
• 
CX-01 given as a 4 mg/kg initial bolus on Day 1, 30 minutes after 
completion of administration of the first dose of idarubicin, followed 
by CX-01 0.25 mg/kg/hour as a continuous 24-hour IV infusion on 
Days 1-5 
• 
Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV 
injection/infusion daily on Days 1and 2 
• 
Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on 
Days 1-5. 
Consolidation therapy 
If there are <5% bone marrow blasts in the bone marrow aspirate performed 
between Days 14-21, a second bone marrow aspiration will be performed within 
1 week after ANC recovers to >1000/μL. If CR is documented, and depending 
on factors including, but not limited to, European Leukemia Net genetic risk 
and co-existing conditions, patients may proceed to consolidation (if not 
proceeding to transplant). Patients who are not in CR at the end of re-induction 
will be taken off study and will complete Early Termination Visit. 
During consolidation, patients will continue in the same treatment group as 
assigned at randomization as follows: 
Group 1: Cytarabine 
• 
Cytarabine 1.0 gram/m2 over 3 hours, every 12 hours on Days 1, 3, and 
5. 
Group 2: Cytarabine + lower dose CX-01 
• 
CX-01 given as a 4 mg/kg initial bolus on Day 1, 30 minutes after 
completion of the first 3-hour infusion of cytarabine, followed 
immediately by CX-01 0.125 mg/kg/hour as a continuous 24-hour IV 
infusion on Days 1-5 for a total of 120 hours of continuous CX-01 
infusion 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 6 of 89 
CONFIDENTIAL 
 
 
 
• 
Cytarabine 1.0 gram/m2 over 3 hours, every 12 hours on Days 1, 3, and 
5. 
Group 3: Cytarabine + higher dose CX-01 
• 
CX-01 given as a 4 mg/kg initial bolus on Day 1, 30 minutes after 
completion of the first 3-hour infusion of cytarabine, followed 
immediately by CX-01 0.25 mg/kg/hour as a continuous 24-hour IV 
infusion on Days 1-5 for a total of 120 hours of continuous CX-01 
infusion 
• 
Cytarabine 1.0 gram/m2 over 3 hours, every 12 hours on Days 1, 3, and 
5. 
Duration of 
Treatment: 
Patients will receive up to two induction cycles and up to two consolidation 
cycles of treatment. 
Duration of Patient 
Participation in 
Study: 
Each patient will participate in the study for approximately 18 months from the 
time of informed consent through final study contact, or until they withdraw 
from the study or the study is terminated by the Sponsor. 
Diagnosis and Main 
Criteria for 
Inclusion: 
To be eligible to participate in the study, patients must meet the following 
criteria: 
1. Newly diagnosed, de novo or secondary, previously untreated AML 
2. Age 60 or above 
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 
to 2 
4. Cardiac ejection fraction ≥45% (as determined by echocardiography or 
multi gated acquisition scan) 
5. Adequate hepatic and renal function determined by the following 
laboratory values: 
• 
Aspartate aminotransferase (AST) or alanine aminotransferase 
(ALT) <2.5 x upper limit of normal (ULN) 
• 
Bilirubin <2.5 x ULN 
• 
Calculated creatinine clearance by Cockcroft Gault formula 
>30 mL/min. 
6. Able to provide informed consent and have signed an approved 
consent form that conforms to federal and institutional guidelines. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 7 of 89 
CONFIDENTIAL 
 
 
 
Exclusion Criteria: 
Patients who meet any of the following criteria will not be eligible to participate 
in the study: 
1. Patients with acute promyelocytic leukemia based on the presence of 
t(15;17)(q22;q12) as determined by karyotyping, fluorescence in situ 
hybridization or polymerase chain reaction 
2. Prior chemotherapy for AML (including investigational therapy); prior 
hydroxyurea to control white blood cell count and a single intrathecal 
administration of cytarabine for CNS prophylaxis is allowed 
3. Prior intensive chemotherapy or stem cell transplantation for treatment 
of myelodysplastic syndrome (prior treatment with hypomethylating 
agents and lenalidomide are allowed) 
4. Presence of central nervous system leukemia 
5. Presence of significant active infection that is not controlled in the 
opinion of the Investigator 
6. Presence of significant active bleeding 
7. History of severe congestive heart failure or other cardiac disease that 
contraindicates the use of anthracyclines, including idarubicin 
8. Pre-existing liver disease (such as CHILD-Pugh Class B or C liver 
disease) 
9. Renal insufficiency which might adversely affect schedule and dose of 
therapy with cytarabine as well as management of tumor lysis 
syndrome 
10. History of drug addiction within the last 6 months 
11. Known history of positive Hepatitis B surface antigens 
12. Known history of positive test for Human Immunodeficiency Virus 
antibodies 
13. Psychiatric or neurologic conditions that could compromise patient 
safety or compliance, or interfere with the ability to give proper 
informed consent 
14. History of other active malignant disease within the past 3 years, other 
than cured basal cell carcinoma of the skin, cured in situ carcinoma of 
the cervix, or localized prostate cancer that has received definitive 
therapy. Such prostate cancer patients who are receiving hormonal 
therapy are eligible 
15. Patients receiving any form of anticoagulant therapy (heparin flushes 
for IV catheter permitted) 
16. Presence of a known bleeding disorder or coagulation abnormality 
(including but not limited to a PTT >40 seconds) or any condition that 
requires maintenance of platelet counts at 50,000/μL or higher 
17. Pregnant or breast feeding patients 
18. Patients of childbearing potential not using adequate contraception. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 8 of 89 
CONFIDENTIAL 
 
 
 
Evaluation: Efficacy 
Bone marrow aspiration will be done between Days 14-21. If LFS is 
documented, an aspirate will be repeated within 1 week after the ANC recovers 
to >1000/μL. Bone marrow aspirate will also be repeated approximately 42 days 
after of initiation of the induction cycle for patients who do not have recovery of 
ANC. Response will be evaluated based on IWG criteria. 
For patients with documented CR, confirmatory bone marrow aspirate slides 
will be submitted to the Sponsor or designee. 
Primary efficacy endpoint 
The primary efficacy endpoint is the morphologic CR rate based on IWG 
criteria. 
Secondary efficacy endpoints 
The secondary endpoints are: 
• 
EFS 
• 
LFS 
• 
OS 
• 
Composite CR rate: incidence of CR + CRi 
• 
Duration of morphologic CR 
• 
30-day mortality 
• 
60-day mortality 
• 
90-day mortality 
• 
Time to neutrophil recovery defined as days from the date of 
randomization until ANC recovered to >1000/μL 
• 
Time to transfusion-independent platelet recovery defined as days from 
the date of randomization until the first day that the platelet count 
recovers to >100,000/μL (provided it is not as a consequence of 
platelet transfusion and provided platelets are then maintained at 
>100,000/μL for the five subsequent days without platelet transfusion). 
Evaluation: Safety 
Key safety endpoints will be assessed by review of summaries of AEs which 
will include only treatment-emergent adverse events (TEAEs), unless otherwise 
stated. Adverse events will be categorized by System Organ Class (SOC) and 
Preferred Term using the Medical Dictionary for Regulatory Activities 
(MedDRA) dictionary (version 14.1), and will be graded according to National 
Cancer Institute-Common Terminology Criteria for Adverse Events 
(NCI-CTCAE) version 4.03. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 9 of 89 
CONFIDENTIAL 
 
 
 
Statistical Methods: 
Sample Size 
A total of 25 evaluable patients per arm will provide 71.8% power for each test 
comparing a dose with control via a Fisher's exact test at 1-sided alpha = 0.15 to 
detect a difference between a control proportion 0.55 and an experimental dose 
proportion 0.80; these tests will be conducted in a fixed sequence: higher dose 
versus control first and lower dose versus control second, with the second test 
considered exploratory (failed) if the first test fails. 
Analysis populations 
The following populations will be considered for data summaries. 
Intent-To-Treat (ITT): All randomized patients. Patients will be analyzed 
according to the treatment to which they are randomized. The ITT Population 
will be the primary analysis set for the efficacy variables. 
Per Protocol (PP): Supporting analyses will be conducted on the PP Population, 
comprising all patients randomized and treated without major protocol 
violations during the trial. This population will be documented before final 
database lock. 
Safety: All patients who received at least one dose of study treatment. Patients 
will be included in the analyses according to the treatment they received. The 
Safety Population will be used in the analyses of all safety endpoints. 
Primary analysis 
The primary efficacy analyses will be based on the ITT Population. Fisher exact 
test will be used to compare the proportion of CRs between each dose and 
control. 
Secondary analysis 
The primary analysis will be repeated using the PP Population as a supportive 
analysis. Complete response rates and confidence intervals will also be reported 
for key subgroups (e.g., randomization strata). Analyses of EFS, LFS, time to 
neutrophil recovery, time to platelet recovery, and OS will be descriptive. 
Kaplan-Meier (KM) estimates will be used to estimate the survival distribution 
for each arm and KM plots will be produced to accompany these analyses. 
Confidence intervals will be reported for medians and KM estimates. Duration 
of response will be analyzed using a similar approach; the analysis will account 
for the competing risk of death and the survival distributions will be estimated 
as cumulative incidence functions. 
Mortality rate at Day 30, Day 60, and Day 90 will be reported using descriptive 
statistics in a manner similar to the reporting of the morphologic CR rate. The 
time to neutrophil and platelet recoveries will be reported using the following 
descriptive statistics: N, mean, standard deviation, median, minimum, 
maximum, and 1st and 3rd quartiles. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 10 of 89 
CONFIDENTIAL 
 
 
 
Statistical Methods: 
Exploratory analysis 
Exploratory analyses will be descriptive. 
Safety analysis 
Safety analysis will be descriptive, based on the Safety Population and will 
involve examination of descriptive statistics and individual patient listings for 
effects of study treatment on clinical safety and tolerability. The safety 
assessment period is from the first dose of study treatment until 30 days 
following the last dose of study treatment. 
All AEs will be categorized by SOC and Preferred Term using MedDRA 
dictionary and graded according to NCI-CTCAE v4.03. Treatment-emergent 
AE summaries will include NCI-CTCAE Grade 3 or higher AEs, and AEs 
resulting in discontinuation of study treatment, AEs resulting in death, deaths 
during the treatment period within 30 days of the last study treatment, deaths 
reported beyond 30 days that are considered study drug-related, and the 
incidence of laboratory values with NCI-CTCAE Grades 3 or 4. Particular 
attention will be upon coagulation parameters and bleeding-related events. Vital 
signs and ECOG performance status, electrocardiograms, and laboratory 
parameters will be summarized descriptively. 
Pharmacokinetic analysis 
Pharmacokinetic analyses will be descriptive. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 11 of 89 
CONFIDENTIAL 
 
 
 
 
TABLE OF CONTENTS 
KEY STUDY PERSONNEL .............................................................................................. 2 
SYNOPSIS .......................................................................................................................... 3 
TABLE OF CONTENTS .................................................................................................. 11 
LIST OF TABLES ............................................................................................................ 15 
LIST OF FIGURES .......................................................................................................... 15 
1. 
INVESTIGATOR/SPONSOR AGREEMENT ......................................................... 16 
2. 
LIST OF ABBREVIATIONS .................................................................................... 17 
3. 
ETHICAL CONSIDERATIONS ............................................................................... 19 
3.1 
Institutional Review Board ................................................................................ 19 
3.2 
Ethical Conduct of the Study ............................................................................. 19 
3.3 
Patient Information and Consent ....................................................................... 19 
4. 
INTRODUCTION ..................................................................................................... 20 
4.1 
Background Information ................................................................................... 20 
4.1.1 
The CXCL12/CXCR4 Axis in Cancer Biology ....................................... 20 
4.1.2 
The CXCL12/CXCR4 Axis in Acute Myeloid Leukemia ....................... 21 
4.1.3 
Clinical Strategies to Block CXCR4 ........................................................ 22 
4.2 
Study Rationale for CX-01 in AML .................................................................. 23 
4.3 
Summary of Studies with CX-01 ...................................................................... 23 
4.3.1 
Preclinical Data ........................................................................................ 23 
4.3.2 
Clinical Data ............................................................................................. 24 
5. 
STUDY OBJECTIVES ............................................................................................. 28 
5.1 
Primary Objectives ............................................................................................ 28 
5.2 
Secondary Objectives ........................................................................................ 28 
6. 
INVESTIGATION PLAN ......................................................................................... 29 
6.1 
Overall Study Design and Plan Description ...................................................... 29 
6.2 
Discussion of Study Design, Including the Choice of Control Groups ............. 31 
6.3 
Selection of Study Population ........................................................................... 31 
6.3.1 
Inclusion Criteria ...................................................................................... 31 
6.3.2 
Exclusion Criteria ..................................................................................... 32 
6.3.3 
Withdrawal and Discontinuation of Patients ............................................ 33 
6.4 
TREATMENT OF PATIENTS ......................................................................... 34 
6.4.1 
Treatments Administered ......................................................................... 34 
6.4.1.1 
Transfusions ...................................................................................... 37 
6.4.1.2 
Dosing and Method of Administration ............................................. 37 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 12 of 89 
CONFIDENTIAL 
 
 
6.4.1.3 
Preparation of CX-01 Infusion .......................................................... 37 
6.4.1.4 
Preparation of CX-01 Intravenous Bolus Dose ................................ 37 
6.4.1.5 
Preparation of CX-01 Continuous Infusion Dose ............................. 37 
6.4.2 
Investigational Product ............................................................................. 38 
6.4.2.1 
Packaging and Labeling .................................................................... 38 
6.4.2.2 
Storage and Stability ......................................................................... 39 
6.4.2.3 
Study Drug Accountability, Reconciliation, and Return .................. 39 
6.4.2.4 
Study Drug Handling and Disposal .................................................. 40 
6.4.3 
Method of Assigning Patients to CX-01 .................................................. 40 
6.4.3.1 
Patient Identification ......................................................................... 40 
6.4.4 
Selection of Doses in the Study ................................................................ 40 
6.4.4.1 
Selection of Dose .............................................................................. 40 
6.4.4.2 
Dose Modifications ........................................................................... 41 
6.4.5 
Prior and Concomitant Medications ......................................................... 42 
6.4.5.1 
Permitted Concomitant Medications ................................................. 42 
6.4.5.2 
Prohibited Concomitant Medications ............................................... 43 
6.4.6 
Treatment Compliance ............................................................................. 43 
6.5 
Study Procedures ............................................................................................... 43 
6.5.1 
Schedule of Study Procedures .................................................................. 43 
6.5.2 
Screening Procedures ............................................................................... 49 
6.5.3 
Randomization .......................................................................................... 49 
6.5.4 
Treatment Procedures ............................................................................... 50 
6.5.5 
Safety Follow-Up Visit............................................................................. 50 
6.5.6 
Early Term Visit ....................................................................................... 51 
6.5.7 
Long Term Follow-Up ............................................................................. 51 
6.6 
EFFICACY AND SAFETY VARIABLES ...................................................... 51 
6.6.1 
Appropriateness of Measurements ........................................................... 51 
6.6.2 
Efficacy Assessments ............................................................................... 52 
6.6.2.1 
Primary Efficacy Assessment ........................................................... 52 
6.6.2.2 
Secondary Efficacy Assessments ...................................................... 52 
6.6.2.2.1 Event-Free Survival ...................................................................... 52 
6.6.2.2.2 Leukemia-Free Survival ............................................................... 52 
6.6.2.2.3 Overall Survival ........................................................................... 52 
6.6.2.2.4 Composite Complete Remission Rate .......................................... 52 
6.6.2.2.5 Duration of Morphologic Complete Remission ........................... 52 
6.6.2.2.6 30-Day, 60-Day and 90-Day Mortality ........................................ 52 
6.6.2.2.7 Neutrophil and Platelet Recovery ................................................. 53 
6.6.3 
Safety Assessments .................................................................................. 53 
6.6.3.1 
Adverse Events ................................................................................. 53 
6.6.3.2 
Definitions ......................................................................................... 53 
6.6.3.2.1 Definition of an Adverse Event .................................................... 53 
6.6.3.2.2 Definition of an Serious Adverse Event ....................................... 55 
6.6.3.2.3 Suspected Unexpected Serious Adverse Reactions ...................... 56 
6.6.3.2.4 Follow-up of Adverse Events/Serious Adverse Events ................ 56 


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6.6.3.2.5 Assessment of Severity ................................................................ 56 
6.6.3.2.6 Causality Assessment ................................................................... 57 
6.6.3.2.7 Action Taken Regarding the Study Drug ..................................... 57 
6.6.3.2.8 Adverse Event Outcome ............................................................... 57 
6.6.3.3 
Pregnancy .......................................................................................... 58 
6.6.3.4 
12-lead Electrocardiogram ................................................................ 58 
6.6.3.5 
Left Ventricular Ejection Fraction .................................................... 58 
6.6.3.6 
Laboratory Assessments ................................................................... 58 
6.6.3.6.1 Bone Marrow Aspirate/Biopsy ..................................................... 59 
6.6.3.7 
Vital Signs and ECOG Performance Status ...................................... 59 
6.6.3.8 
Physical Examination ........................................................................ 59 
6.6.4 
Reporting Serious Adverse Events ........................................................... 59 
6.6.4.1 
Expected Adverse Events ................................................................. 60 
6.6.4.2 
Investigator’s Notification of the Sponsor ........................................ 60 
6.6.4.3 
Notification to the Independent Review Board ................................ 61 
6.6.4.4 
Notification to the Authorities .......................................................... 61 
6.6.4.5 
Sponsor’s Notification to the Investigational Site ............................ 61 
6.6.5 
Data and Safety Monitoring Committee ................................................... 61 
6.6.6 
Pharmacokinetics ...................................................................................... 61 
6.7 
Data Quality Assurance ..................................................................................... 62 
6.8 
Statistical Methods ............................................................................................ 62 
6.8.1 
Determination of Sample Size .................................................................. 62 
6.8.2 
Patient Populations Analyzed ................................................................... 62 
6.8.3 
General Considerations ............................................................................ 63 
6.8.4 
Demographics and Other Baseline Characteristics .................................. 63 
6.8.4.1 
Patient Disposition ............................................................................ 63 
6.8.4.2 
Patient and Disease Characteristics .................................................. 64 
6.8.5 
Medical and Surgical History ................................................................... 64 
6.8.6 
Concomitant Therapy ............................................................................... 64 
6.8.7 
Extent of Study Drug Exposure and Compliance ..................................... 65 
6.8.8 
Efficacy Analysis ...................................................................................... 65 
6.8.8.1 
Primary Efficacy Outcome Measure ................................................. 65 
6.8.8.2 
Secondary Efficacy Outcome Measures ........................................... 65 
6.8.9 
Subgroup Analysis ................................................................................... 65 
6.8.10 
Safety Analysis ......................................................................................... 65 
6.8.10.1 
Adverse Events ................................................................................. 65 
6.8.10.2 
Clinical Laboratory Assessments ...................................................... 66 
6.8.10.3 
Vital Signs and ECOG Performance Status ...................................... 66 
6.8.10.4 
Electrocardiogram ............................................................................. 66 
6.8.11 
Pharmacokinetic Analysis ........................................................................ 66 
7. 
RISKS AND BENEFITS ........................................................................................... 66 
8. 
INVESTIGATORS REGULATORY OBLIGATIONS ............................................ 67 
8.1 
Pre-study Documentation .................................................................................. 67 


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8.2 
Electronic Data Capture .................................................................................... 67 
8.3 
Adverse Event Reporting .................................................................................. 68 
8.4 
Review of Source Records ................................................................................ 68 
8.5 
Monitoring of the Study .................................................................................... 68 
8.6 
Protocol Amendments ....................................................................................... 68 
8.7 
Protocol Deviations ........................................................................................... 69 
8.8 
Change in Investigator....................................................................................... 69 
8.9 
Criteria for Termination of the Study or Study Center/Site .............................. 69 
8.9.1 
Early Termination of the Study ................................................................ 69 
8.10 Clinical Study Report ........................................................................................ 70 
8.11 Confidentiality ................................................................................................... 70 
8.12 Records Retention ............................................................................................. 70 
9. 
REFERENCES .......................................................................................................... 71 
10. APPENDICES ........................................................................................................... 76 


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LIST OF TABLES 
 
Table 2—1: List of Abbreviations ................................................................................................................. 17 
Table 4—1 Clinical Data in Conditions Other than Acute Myeloid Leukemia ............................................. 25 
Table 6—1 Induction/Re-induction Cycle Schedule of Study Procedures .................................................... 44 
Table 6—2 Consolidation Cycle Schedule of Study Procedures ................................................................... 47 
 
 
LIST OF FIGURES 
 
Figure 6—1 Study Design ............................................................................................................................. 30 
Figure 6—2 Structure of CX-01 .................................................................................................................... 38 


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1. 
INVESTIGATOR/SPONSOR AGREEMENT 
 
This protocol was designed and will be conducted, recorded, and reported in accordance 
with the principle of Good Clinical Practice (GCP) as stated in the International 
Conference of Harmonisation (ICH) of Technical Requirements for Registration of 
Pharmaceuticals for Human Use and any applicable national and regional laws. I have 
read and agree to abide by the requirements of this protocol. 
 
 
 
 
 
 
Principal Investigator 
Date 
 
 
 
Sponsor Signature: 
 
 
 
 
 
 
Stephen Marcus, M.D. 
Date 
Chief Executive Officer 
Cantex Pharmaceuticals, Inc. 


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2. 
LIST OF ABBREVIATIONS 
 
Table 2—1: List of Abbreviations 
 
Abbreviation 
Definition 
AE(s) 
adverse event(s) 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
anti-factor Xa 
anti-factor10a 
API 
active pharmaceutical ingredient 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
BP 
blood pressure 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CAF 
cancer-associated fibroblast 
CIT 
chemotherapy-induced thrombocytopenia 
COPD 
chronic obstructive pulmonary disease 
CR 
complete remission 
CRi 
complete remission without recovery of neutrophils 
and/or platelets 
CRO 
contract research organization 
CRp 
complete remission without recovery of platelets 
CSA 
clinical study agreement 
CSR 
clinical study report 
CX-01 
2-O, 3-O desulfated heparin (ODSH) 
D 
day 
Disc. 
discontinuation 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EFS 
event-free survival 
ELN 
European Leukemia Net 
FDA 
Food and Drug Administration 
FU 
follow-up 
GCP 
Good Clinical Practice 
cGMP 
current Good Manufacturing Practice 
HIT 
heparin-induced thrombocytopenia 
HSC 
hematopoietic stem cells 
IB 
Investigator Brochure 
ICF 
informed consent form 
ICH 
International Conference of Harmonisation 
IND 
Investigational New Drug 
INR 
international normalized ratio 


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Abbreviation 
Definition 
IRB 
Institutional Review Board 
ITT 
Intent-To-Treat 
IV 
intravenous 
IWG 
International Working Group 
IxRS 
Interactive Web/Voice Response System 
KM 
Kaplan-Meier 
LDH 
lactate dehydrogenase 
LFS 
leukemia-free state 
LFT 
liver function test 
LMWH 
low molecular weight heparin 
LSC 
leukemic stem cells 
MedDRA 
Medical Dictionary for Regulatory Activities 
MUGA 
multi gated acquisition 
NCI-CTCAE 
National Cancer Institute-Common Terminology 
Criteria for Adverse Events 
ODSH 
2-O, 3-O desulfated heparin 
OS 
overall survival 
PF4 
platelet factor 4 
PFS 
progression-free survival 
PLE 
protein losing enteropathy 
PP 
Per Protocol 
PT 
prothrombin time 
SAE(s) 
serious adverse event(s) 
SAP 
statistical analysis plan 
SCLC 
small cell lung cancer 
SD 
standard deviation 
SOC 
System Organ Class 
SUSAR(s) 
suspected unexpected serious adverse reaction(s) 
TEAE(s) 
treatment-emergent adverse event(s) 
UFH 
unfractionated heparin 
ULN 
upper limit of normal 
WBC(s) 
white blood cell(s) 
WHO-DD 
World Health Organization Drug Dictionary 


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3. 
ETHICAL CONSIDERATIONS 
 
3.1 
Institutional Review Board 
 
The protocol and informed consent form (ICF) will be reviewed and approved by the 
Institutional Review Board (IRB). The Sponsor will supply relevant material for the 
Investigator to submit to the IRB for the protocol’s review and approval. Documentation 
of the IRB unconditional approval of the protocol and the written ICF statement will be 
transmitted to the Investigator. 
 
The Investigator must submit and, where necessary, obtain approval from IRB for all 
subsequent protocol amendments. Approval for protocol amendments will be transmitted 
in writing to the Investigator. If requested, the Investigator will permit audits by the IRB 
and regulatory inspections by providing direct access to source data/documents. 
 
The Investigator will provide the IRB with progress reports at required intervals (not to 
exceed one year) and a Study Progress Report following the completion, termination, or 
discontinuation of the Investigator’s participation in the study. 
 
3.2 
Ethical Conduct of the Study 
 
The study procedures outlined in this protocol will be conducted in accordance with the 
ethical principles that have their origin in the Declaration of Helsinki, and that are 
consistent with the ICH consolidated Guideline E6 for GCP, and the applicable 
national/regional laws and regulatory requirement(s). 
 
3.3 
Patient Information and Consent 
Written informed consent for the study will be obtained from all patients before any 
protocol-specific procedures are conducted. The ICF generated by the Sponsor or 
designee will be approved (along with the protocol) by the IRB. 
 
Information about the study will be given to the patient both verbally and in writing. The 
written patient information sheet will explain the objectives of the study and its potential 
risk and benefits. The patient should have adequate time to read the information sheet and 
to ask the Investigator any questions. The Investigator must be satisfied that the patient 
has understood the information provided before written consent is obtained. If there is 
any doubt as to whether the patient has understood the written and verbal information, the 
patient should not enter the study. 
 
If a patient agrees to participate, he/she will be asked to sign and date the study ICF 
which will be retained by the Investigator. A copy of the signed ICF will be given to the 
patient. The informed consent process must be documented in the patient’s source 
documents. The original ICF must be retained by the Investigator and made available for 
inspection by the Study Monitor. 


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4. 
INTRODUCTION 
 
This is a phase II study to evaluate 2-O, 3-O desulfated heparin (CX-01), a low molecular 
weight heparin (LMWH) derivative with inhibitory effects on the CXCL12/CXCR4 axis, 
a pathway that has been shown to be important in cancer stem cell survival, proliferation, 
migration, and chemotaxis. It is proposed that the addition of CX-01 at two dose levels to 
idarubicin + cytarabine may be of benefit in the treatment of acute myeloid leukemia 
(AML). 
 
At present, CX-01 has been administered to 189 adults and children in phase I and II trials 
in which a highly favorable safety profile was observed. 
 
4.1 
Background Information 
 
Heparin was discovered almost 100 years ago (1), and through most of its life has been 
employed as an anticoagulant to treat or prevent vascular thrombosis. However, because 
of heparin binding motifs on a host of proteins, this glycosaminoglycan has multiple 
pharmacologic effects that are not dependent upon anticoagulation (2). In cancer, these 
non-anticoagulant actions, and most notably its ability to disrupt the CXCL12/CXCR4 
axis, offers an intriguing set of therapeutic possibilities for using heparin as adjunctive 
treatment to conventional therapy. These therapeutic possibilities are, however, severely 
limited by unacceptable anticoagulant effects at heparin doses required for relevant non- 
anticoagulant pharmacologic activity. This observation led to the development of a low 
anticoagulant CX-01 that retains the broad range of biologic activities of heparin, with 
only a small fraction of its anticoagulant activities. 
 
Acute myelogenous leukemia afflicted 18,860 patients in the United States in 2014 and 
resulted in 10,460 deaths. Despite incremental advances (3,4), the mainstay of AML 
induction therapy continues to be variations on a 7-day infusion of cytarabine and 3 days 
of an anthracycline (“7 + 3”), an approach three decades old (5). Relapses are believed to 
be due to quiescent CD34+CD38- leukemic stem cells (LSCs) nestled in the marrow 
stromal niche, where they are resistant to the cytotoxic effects of chemotherapy. 
 
4.1.1 
The CXCL12/CXCR4 Axis in Cancer Biology 
The CXCL12/CXCR4 axis has recently been suggested as a new therapeutic target in 
lung cancer (6,7). CXCL12 (also known as Stromal Cell Derived Factor-1) was first 
described as a CXC chemokine produced locally within the bone marrow compartment 
that provides a homing signal for hematopoietic stem cells (HSCs) by ligation of its 
G-protein coupled receptor (CXCR4) to the surface of HSCs. Ligation of CXCR4 
activates a number of signaling pathways, in particular the phosphatidylinositol 3-kinase 
(PI3K)/Akt pathway, which promotes stem cell survival, proliferation, migration, and 
chemotaxis (7). 
 
More recently, it has been appreciated that splice variants of CXCL12 are also produced 
in high concentrations in brain, lung, colon, heart, kidney and liver, and that these 
CXCR4 receptors are prominently expressed on the cell membranes of many cancer cells, 


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particularly cancer stem cells (7). This emerging research supports a role for the 
CXCL12/CXCR4 axis in mediating the invasion/migration by cancer cells and cancer 
stem cells into the “fertile soil” sites commonly associated with metastasis. Thus, it is 
proposed that local production of CXCL12 within metastasis-prone sites promotes the 
chemotaxis of cancer cells and cancer stem cells into these sites through interaction with 
the CXCR4 on the membranes of cancer cells. 
 
In addition, the CXCL12/CXCR4 axis appears to be important in cancer cell proliferation 
and neovascularization, and is intimately involved in recruiting cancer-associated 
fibroblasts (CAF) that provide the mesenchymal matrix support for growing tumors and 
further metastases (7). Thus, a major promoter of CXCL12 and CXCR4 expression 
within a tumor is its hypoxic core, which gives rise to hypoxia inducible factor 1α. 
CXCL12 is also produced abundantly by CAFs and inflammatory macrophages within 
the tumor. Once stimulated by CXCL12, tumor cell associated CXCR4 becomes a major 
mediator of tumor cell interaction with extracellular matrix proteins (i.e., laminin, 
fibronectin, collagen), as well as a regulator of CD44 and integrin-mediated cancer and 
cancer stem cell adhesion (though CXCR4 itself is not directly involved in cell adhesion). 
 
4.1.2 
The CXCL12/CXCR4 Axis in Acute Myeloid Leukemia 
Normal CD34+CD38- HSCs migrate to and are anchored in the bone marrow by 
chemotactic signals produced by cells in the marrow stroma (8,9,10,11). Foremost of 
these signals is the CXC chemokine CXCL12 (stem cell derived factor-1), which ligates 
chemokine receptor 4 (CXCR4) on the HSC surface. This signaling activates directional 
Rho/Rac-mediated migration toward and attachment in the bone marrow environment 
through enrichment of pseudopodia with adhesion receptors such as very late antigen-4 
and others. CXCL12/CXCR4 signaling also activates phosphatidylinositol-3-kinase and 
its downstream effector protein kinase B, providing enhanced survival (10). In the 
marrow, HSCs shuttle between an endosteal osteoblastic niche inducing quiescence and a 
sinusoidal endothelial vascular niche promoting proliferation and differentiation (8). 
Recent evidence suggests that quiescence in the endosteal niche is maintained by close 
association with megakaryocytes (12,13). Megakaryocytes negatively regulate HSC 
proliferation through secretion of platelet factor-4 (PF4), which also enhances integrin- 
mediated endothelial adhesion during bone marrow homing (14). 
 
There is substantial evidence that LSCs employ the same CXCL12-, CXCR4-, adhesion 
molecule-dependent mechanisms as normal HSCs to home toward a marrow niche and 
maintain themselves in a quiescent, protected state (8,14,15,16,17,18,19,20,21,22,23). 
CXCR4 is an unfavorable prognostic marker in AML (24,25,26,27,28), and its high 
expression on CD34+ AML is associated with the poor survival in patients with Fms-like 
tyrosine kinase-3 /internal tandem duplication mutations. Conversely, disrupting CXCR4 
signaling inhibits transmigration, survival and chemotherapy resistance in vitro 
(29,30,31,32) and tumor growth in AML xenografts (32,33,34,35). Clinical experience 
with the CXCR4 inhibitor Plerixafor in AML is just beginning (36,37). Short term daily 
subcutaneous administration of Plerixafor for up to 7 days for stem cell mobilization is 
well tolerated (38). However, cardiac toxicity arose when it was administered as a daily 
intravenous (IV) infusion or subcutaneous injection for 11-14 days (39). This questions 


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the safety of long term continuous blockade of CXCR4, a receptor also important in 
repair of injured tissues. 
 
An alternative approach to blocking CXCR4 signaling is direct interference with its 
ligand CXCL12. Heparin, a glycosaminoglycan used as an anticoagulant, avidly binds to 
a cluster of cationic amino acids on the CXCL12 surface that overlaps with the CXCR4 
binding region (40,41). Heparin inhibition of CXCL12 is diminished by removal of 6-O, 
but not 2-O sulfates (42), but is apparent only at concentrations of 20 U or approximately 
3 µg/mL (42,43), which exceed therapeutic heparin plasma levels for anticoagulation by 
10-fold (44). Low anticoagulant 2-O, 3-O desulfated heparin (ODSH, also known as 
CX-01, Figure 6—2) is a porcine intestinal heparin derivative that retains many heparin 
anti-inflammatory properties. Additionally, CX-01 binds PF4 with affinity similar to 
heparin, but the CX-01/PF4 complex does not bind antibodies that produce platelet 
activation and mediate heparin-induced thrombocytopenia (HIT). Furthermore, 
megakaryopoiesis is negatively regulated by PF4 and anti-PF4 blocking antibodies 
diminish chemotherapy-induced thrombocytopenia (CIT) in mice. CX-01 binds to and 
reverses biologic activities of PF4 and mitigates CIT in transgenic mice that overexpress 
PF4. 
 
Based on these considerations, we conducted a pilot study combining CX-01 with 
standard chemotherapy for the treatment of AML. Results, as described below, suggest 
that CX-01 increases the complete remission (CR) rate and enhances count recovery. In 
addition, we show that CX-01 potently inhibits CXCL12 ligation of CXCR4 in vitro at 
concentrations that do not produce anticoagulation. 
 
4.1.3 
Clinical Strategies to Block CXCR4 
A number of strategies have been tested to block CXCR4, among these are AMD3100 
(Genzyme), BKT140 (Biokine Therapeutics), MSX-122 (Med Koo Biosciences), 
unfractionated heparin (UFH) and LMWH (various). 
 
AMD3100 (known as Plerixafor and Mozobil), has gained Food and Drug Administration 
approval for the mobilization of stem cells. AMD3100, when used with another small 
molecule CXCR4 inhibitor, BKT140, acts synergistically with chemotherapy in human 
non-small cell lung cancer under experimental conditions (45,46,47) as well as against 
small cell lung cancer (SCLC) in vitro and in animal models (48,49,50,51). 
 
Short term daily subcutaneous administration of AMD3100 for up to 7 days in humans 
for stem cell mobilization is well tolerated (52), but when administered as a daily IV 
infusion or subcutaneous injection for 11-14 days, as an HIV treatment in humans, it was 
associated with cardiac toxicity (53,54). MSX-122, also developed for stem cell 
mobilization, is a partial CXCR4 antagonist which in animal studies appears to be 
tolerated in longer term regimens, however, MSX-122 has not as yet been tested in 
humans. 
 
Heparins are effective inhibitors of CXCL12. Recently, UFH has been shown to inhibit 
CXCL12 in a manner not dependent on its anticoagulant activity (42). Binding of heparin 


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produces a steric hindrance of CXCR4 binding to CXCL12 (55) when this negatively 
charged glycosaminoglycan binds to a concentration of cationic amino acids that overlap 
with the CXCR4 binding site (55). However, even greater effectiveness might be 
achieved using, CX-01, a low anticoagulant heparin, that would enable effective 
CXCL12 blocking without the risk of anticoagulation. 
 
4.2 
Study Rationale for CX-01 in AML 
 
CX-01 is a rationally engineered complex carbohydrate derived from heparin that may 
represent a safer inhibitor of the CXCL12/CXCR4 axis. 
 
Differential anticoagulant effect relative to heparin: Heparin is more than 200 fold more 
potent than CX-01 as an anticoagulant. The anticoagulant effect of CX-01 begins to 
appear at a plasma concentration that is approximately 2-fold higher than the plasma 
concentrations achieved in normal volunteer and patient studies (25 µg/mL); at these 
concentrations it is anticipated that CX-01 can be employed clinically with little if any 
anticoagulant effect (56). 
 
Reduced antigenicity relative to heparin: HIT is a potential clinical complication of 
heparin administration that results from the formation of an antibody to the PF4/heparin 
complex, which in turn may cause thrombocytopenia and thromboembolism (57). CX-01 
binds PF4 with an affinity similar to heparin, but the CX-01/PF4 complex does not 
activate platelets because it does not bind HIT antibodies and, unlike heparin/PF4, does 
not stimulate additional antibody production (56,58,59). 
 
Platelet and white blood cell (WBC) recovery following chemotherapy: In patients with 
metastatic pancreatic cancer receiving gemcitabine + nab-paclitaxel, and in patients with 
AML receiving induction therapy with idarubicin and cytarabine, CX-01 appears to 
accelerate both platelet and WBC recovery after high dose chemotherapy. The 
acceleration of platelet and WBC recovery may be explained by a blocking effect of 
CX-01 on the inhibitory action of PF4 in marrow myeloid and megakaryocyte 
development after chemotherapy (60,61,62). In separate but related research, Cantex is 
collaborating with the National Institute of Health and other federal agencies to develop 
CX-01 as a medical countermeasure to radiation poisoning, where refractory 
thrombocytopenia is a major concern. 
 
Thus, CX-01 may offer benefits to AML patients without the risks of other heparin 
derivatives, namely blocking of the CXCL12/CXCR4 axis without the accompanying 
risks of anticoagulation or of HIT; it may also benefit AML patients receiving intensive 
chemotherapy by accelerating platelet and WBC recovery times. 
 
4.3 
Summary of Studies with CX-01 
4.3.1 Preclinical Data 
 
In rats the no-observed-adverse-effect-level (NOAEL) was 48 mg/kg/day, and in dogs it 
was 160 mg/kg/day. The only observed adverse effect in either species was the expected 


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occurrence of hemorrhage at high doses of drug, when coagulation parameters were 
prolonged. No adverse effect on cardiac conduction has been observed in porcine studies 
of myocardial infarction. There were no adverse effects of CX-01 administration on the 
cardiovascular profile in dogs or on the respiratory parameters in albino rats. 
 
4.3.2 Clinical Data 
 
As of October 9, 2015, a total of 188 patients had been exposed to CX-01 at doses of 4 to 
20 mg/kg as a bolus and doses of 0.125 to 3.9 mg/kg/hour as a continuous IV infusion for 
durations of 12 to 168 hours. 
 
• 54 healthy subjects who participated in three phase I trials 
• 78 subjects with exacerbation of chronic obstruction pulmonary disease (COPD) 
in a phase II study 
 
• 35 patients with metastatic pancreatic cancer 
• 5 patients with exacerbation of protein losing enteropathy (PLE) secondary to 
Fontan procedure (phase II study) 
 
• 12 patients with AML 
• 4 pediatric patients with recurrent solid tumors. 


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Table 4—1 Clinical Data in Conditions Other than Acute Myeloid Leukemia 
 
Study 
Number 
Phase 
Indication 
Number of 
Patients 
Study Drug and 
Dose 
Study Endpoints 
Study Results 
PGX-ODSH- 
2013-AML-1 
Pilot 
AML 
N=12 
Cytarabine at 
100 mg/m2/day 
as a continuous 
infusion for 7 
days; Idarubicin 
12 mg/m2 daily 
for 3 days; CX- 
01 given as a 
4 mg/kg bolus 
followed by 
6 mg/kg/day as a 
continuous 
infusion for 
7 days (168 
hours) 
Primary 
• Safety and tolerability of 
CX-01 when combined 
with chemotherapy 
• Obtain preliminary 
evidence of the effect of 
CX-01 on platelet 
transfusion independence 
Secondary 
Effect of CX-01 on CR rate, 
platelet nadir count, number of 
platelet transfusions, induced 
side effects 
Combination was associated with CR 
rate of 92%. Hematologic recovery was 
rapid. Even though a small population 
was treated, data suggests that CX-01 
could not only be a chemotherapy 
sensitizer for traditional 7+3 induction 
therapy but could also accelerate count 
recovery after induction. 
CX-01 was found to be safe and well 
tolerated with no unexpected SAEs. 
PGX-ODSH- 
2006 
II 
Exacerbation 
of COPD 
N=156, 
equally 
randomized 
to receive 
standard 
treatment of 
COPD with 
or without 
CX-01 
CX-01 given as a 
8 mg/kg bolus 
followed by 
CX-01, 0.375 
mg/kg/h for 
96 hours 
Primary 
Composite of failure to 
discharge from hospital in a 
timely manner + relapse within 
21 days of hospital discharge 
Secondary 
FEV1, FEV1/FVC, Borg 
CR10Scale, 6-minute Walk 
Test, BODE index and hs-CRP 
There was no evidence of effect or 
efficacy of CX-01 compared to placebo 
for the primary endpoint for Intent-to- 
Treat (ITT) or Per Protocol (PP) 
Populations. No statistical significant 
effects were shown for the secondary 
endpoints. 
CX-01 was well tolerated. A few 
instances of minor/moderate bleeding 
and only one case of major bleeding. 
Some predictable changes were noted 
for AST and ALT with CX-01 
treatment. No other clinical and 
laboratory parameters showed 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 26 of 89 
CONFIDENTIAL 
 
 
 
 
 
 
Study 
Number 
Phase 
Indication 
Number of 
Patients 
Study Drug and 
Dose 
Study Endpoints 
Study Results 
significant changes from baseline. Eight 
deaths were reported (placebo=5 and 
CX-01=3). Those three were not related 
to CX-01 occurred post treatment. 
PGX-ODSH- 
2009-PLE 
II 
Protein losing 
enteropathy 
(PLE) 
secondary to 
Fontan 
procedure 
N=5, 
Pediatric and 
young adult 
population 
CX-01, 96 hour 
IV infusion at 
0.125 mg/kg/h or 
CX-01, 96 hour 
IV infusion at 
0.250 mg/kg/h 
Safety, reduction of symptoms 
of PLE, reduction of alpha-1 
antitrypsin levels 
Though all patients had some subjective 
clinical improvement, CX-01 did not 
show clear effects on efficacy 
biomarkers. Due to extremely low 
patient enrollment and a lack of efficacy, 
the study was terminated early. 
22 AEs and two unrelated SAEs were 
reported. All AEs were considered mild 
or moderate in intensity. 
PGX-ODSH- 
2011-PC 
II 
Metastatic 
pancreatic 
cancer 
N=60, with 
35 patients 
receiving 
CX-01 in 
conjunction 
with 
chemotherapy 
and 25 
randomized 
to receive 
chemotherapy 
alone 
Gemcitabine 
(1000 mg/m2) 
and nab- 
paclitaxel 
(125 mg/m2) on 
days 1, 8, and 15 
for 3 weeks with 
or without CX-01 
(4 mg/kg bolus 
followed by 
CX-01, 0.375 
mg/kg/h for 48 
hours) starting 
with the first dose 
of chemotherapy 
on Days 1, 8, and 
Primary 
Progression-free survival (PFS) 
No statistically significant change of 
PFS and OS was noted in patients 
receiving CX-01. Comparing Day 1 and 
Day 15 platelet counts in patients 
receiving gemcitabine + nab-paclitaxel 
with or without CX-01; a statistically 
significant increase was observed 
favoring CX-01 treatment. 
Among the 35 patients in this study 
treated with CX-01, 3 serious adverse 
events (pulmonary embolus, type II 
diabetes, and Grade 2 peripheral edema) 
were reported. The thromboembolic 
events were considered to be related to 
Trousseau’s syndrome and underlying 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 27 of 89 
CONFIDENTIAL 
 
 
 
 
 
 
Study 
Number 
Phase 
Indication 
Number of 
Patients 
Study Drug and 
Dose 
Study Endpoints 
Study Results 
15 
disease. 
Abbreviations: AE=adverse event, ALT=alanine aminotransferase, AML=acute myeloid leukemia, AST=aspartate aminotransferase, COPD=chronic obstruction 
pulmonary disease, CR=complete remission, FEV1=forced expiratory volume in 1 second, FVC=forced vital capacity, hs-CRP=high sensitivity C-reactive 
protein, ITT=Intent-to-Treat, IV=intravenous, N=number, OS=overall survival, PFS=progression-free survival, PLE=protein losing enteropathy, PP=Per 
Protocol, SAE=serious adverse event. Note: Further details can be found in the Investigator’s Brochure (63). 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 28 of 89 
CONFIDENTIAL 
 
 
5. 
STUDY OBJECTIVES 
 
This randomized, phase II study of CX-01 is designed to assess the effect of adding 
CX-01 at one of the two different dose levels to standard induction and consolidation 
therapy for newly diagnosed patients with AML. 
 
5.1 
Primary Objectives 
 
The primary objectives are: 
 
• To assess whether CX-01, administered at any or all studied dose levels in 
conjunction with standard induction therapy for AML increases the morphologic 
CR rate based on International Working Group (IWG) criteria 
 
• To assess the safety and tolerability of CX-01, administered at two studied dose 
levels in conjunction with standard induction therapy for AML. 
 
5.2 
Secondary Objectives 
 
The secondary efficacy objectives are: 
 
To assess whether CX-01, administered at any or all studied dose levels in conjunction 
with standard induction and consolidation therapy for AML improves: 
 
• Event-free survival (EFS) 
• Leukemia-free survival (LFS) 
• Overall survival (OS) 
• Composite CR rate: incidence of CR + CRi, which is CR without recovery of 
neutrophils and/or platelets (ANC may be <1000 μL and/or platelet count 
<100,000/μL). 
 
• Duration of morphologic CR 
• 30-day mortality (in the induction cycle) 
• 60-day mortality (in the induction cycle) 
• 90-day mortality (in the induction cycle) 
• Neutrophil recovery 
• Platelet recovery. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 29 of 89 
CONFIDENTIAL 
 
 
6. 
INVESTIGATION PLAN 
 
6.1 
Overall Study Design and Plan Description 
 
This is an exploratory phase II, open-label, randomized, multicenter, parallel group trial 
to determine whether there is evidence that the addition of either or both different dose 
levels of CX-01 to standard induction therapy (idarubicin + cytarabine) and consolidation 
therapy has an additive therapeutic effect in newly diagnosed AML patients when 
compared to patients receiving standard induction chemotherapy alone. 
 
Approximately 75 patients will be randomized in a 1:1:1 ratio to one of the following 
treatment groups: 
 
• Group 1: Idarubicin + Cytarabine, OR 
• Group 2: Idarubicin + Cytarabine plus lower dose CX-01 (0.125 mg/kg/hour), 
OR 
 
• Group 3: Idarubicin + Cytarabine plus higher dose CX-01 (0.25 mg/kg/hour) 
Eligible patients who meet the inclusion criteria and do not meet any of the exclusion 
criteria and have provided informed consent will be enrolled in the study. Each patient 
will participate in the study for approximately 18 months from the time of informed 
consent through final study contact, or until they withdraw from the study or the study is 
terminated by the Sponsor. 
 
Overall survival data will be collected every 3 months until death or until the end of study 
by the investigational sites. The end of study will occur approximately 18 months after 
the last patient is randomized. 
 
A Data and Safety Monitoring Committee (DSMC) will meet periodically to review the 
safety of the study (see Section 6.6.5). Details describing the DSMC process and 
procedures will be outlined in a separate DSMC Charter. 
 
Adverse events (AEs) will be collected from time of informed consent and continue until 
30 days after the last study treatment is administered. Longer follow-up and collection of 
AEs may be required for patients that do not have an absolute neutrophil count (ANC) 
recovery within 42 days (i.e., until the recovery or the reason for no recovery is 
diagnosed) after the last induction or consolidation cycle. 
 
A flow diagram of the study design is shown in Figure 6—1. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 30 of 89 
 
 
 
Figure 6—1 Study Design 
 
 
 
 
 
Abbreviations: AML=acute myeloid leukemia 
Note: It is expected that approximately 90 patients will be screened to identify 75 patients for 
randomization. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 31 of 89 
CONFIDENTIAL 
 
 
6.2 
Discussion of Study Design, Including the Choice of Control Groups 
 
Approximately 75 patients will be randomized in a 1:1:1 ratio to receive standard 
induction and consolidation therapy with or without CX-01 at two different doses (lower 
and higher dose). 
The anthracycline/cytarabine regimen using idarubicin (9-12 mg/m2 daily) is considered a 
standard therapy for the majority of newly diagnosed patients with AML (64). Complete 
remissions are achieved in approximately 50% to 75% of patients (65). Dosing studies 
with continuous infusion cytarabine demonstrated that 100 mg/m2 was as effective as 
200 mg/m2 (66,67). 
The need for post remission therapy, following successful induction therapy, has been 
established in a number of clinical trials. It is presumed that most patients still have 
residual disease after the completion of induction chemotherapy (68). The standard 
treatment option includes consolidation therapy with intensive cytarabine-based 
chemotherapy regimens or allogeneic stem cell transplant. 
 
6.3 
Selection of Study Population 
 
6.3.1 Inclusion Criteria 
 
To be eligible to participate in the study, patients must meet the following criteria: 
 
1. Newly diagnosed, de novo or secondary, previously untreated AML 
 
2. Age 60 or above 
 
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 
(Appendix A) 
 
4. Cardiac ejection fraction ≥45% (as determined by echocardiography or multi 
gated acquisition [MUGA] scan) 
 
5. Adequate hepatic and renal function determined by the following laboratory 
values: 
 
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
<2.5 x upper limit of normal (ULN) 
 
• Bilirubin <2.5 x ULN 
• Calculated creatinine clearance by Cockcroft Gault formula >30 mL/min 
(see Appendix C). 
 
6. Able to provide informed consent and have signed an approved consent form that 
conforms to federal and institutional guidelines. 


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CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 32 of 89 
CONFIDENTIAL 
 
 
6.3.2 Exclusion Criteria 
 
Patients who meet any of the following criteria will not be eligible to participate in the 
study: 
 
1. Patients with acute promyelocytic leukemia based on the presence of 
t(15;17)(q22;q12) (69) as determined by karyotyping, fluorescence in situ 
hybridization or polymerase chain reaction 
 
2. Prior chemotherapy for AML (including investigational therapy); prior 
hydroxyurea to control WBC count and a single intrathecal administration of 
cytarabine for CNS prophylaxis is allowed 
 
3. Prior intensive chemotherapy or stem cell transplantation for treatment of 
myelodysplastic syndrome (prior treatment with hypomethylating agents and 
lenalidomide are allowed) 
 
4. Presence of central nervous system leukemia 
 
5. Presence of significant active infection that is not controlled in the opinion of the 
Investigator 
 
6. Presence of significant active bleeding 
 
7. History of severe congestive heart failure or other cardiac disease that 
contraindicates the use of anthracyclines, including idarubicin 
 
8. Pre-existing liver disease (such as CHILD-Pugh Class B or C liver disease; see 
Appendix D) 
 
9. Renal insufficiency which might adversely affect schedule and dose of therapy 
with cytarabine as well as management of tumor lysis syndrome. 
 
10. History of drug addiction within the last 6 months 
 
11. Known history of positive Hepatitis B surface antigens 
 
12. Known history of positive test for Human Immunodeficiency Virus antibodies 
 
13. Psychiatric or neurologic conditions that could compromise patient safety or 
compliance, or interfere with the ability to give proper informed consent 
 
14. History of other active malignant disease within the past 3 years, other than cured 
basal cell carcinoma of the skin, cured in situ carcinoma of the cervix, or localized 
prostate cancer that has received definitive therapy. Such prostate cancer patients 
who are receiving hormonal therapy are eligible 
 
15. Patients receiving any form of anticoagulant therapy (heparin flushes for IV 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 33 of 89 
CONFIDENTIAL 
 
 
catheter permitted) 
 
16. Presence of a known bleeding disorder or coagulation abnormality (including but 
not limited to aPTT >40 seconds) or any condition that requires maintenance of 
platelet counts at 50,000/μL or higher 
 
17. Pregnant or breast feeding patients 
 
18. Patients of childbearing potential not using adequate contraception. 
 
6.3.3 Withdrawal and Discontinuation of Patients 
 
Patients are free to withdraw consent and/or discontinue participation in the study at any 
time, without prejudice to further treatment. A patient’s participation in the study may 
also be discontinued at any time at the discretion of the Investigator or Sponsor. 
 
The following may be justifiable reasons for the Investigator or Sponsor to discontinue a 
patient from treatment: 
 
• The patient was erroneously included in the study (i.e. was found to be ineligible) 
• The patient experiences an intolerable or unacceptable AE 
• The patient is unable to comply with the requirements of the protocol 
• The patient participates in another investigational study without the prior written 
authorization of the Sponsor or its designee 
 
• The patient’s participation in the study presents a significant safety concern. 
Patients who experience Grade 4 increases in AST, ALT or bilirubin (e.g., increase in 
AST or ALT >20 x ULN; increase in total bilirubin to >10 x ULN) will be discontinued 
from the study, if the Investigator judges that the laboratory abnormalities are potentially 
related to study treatment. Patients discontinued for this reason will not be re-challenged 
and will be followed until resolution of abnormal liver function tests. 
 
Patients who are discontinued from study due to an AE will be closely monitored until 
the resolution or stabilization of the AE. 
 
Patients who received at least one dose of study drug and who are discontinued from 
treatment, but not withdrawn from the study, will be asked to complete all evaluations for 
early termination (Early Termination/End of Study Visit). 
 
Patients who discontinue from the study will not be replaced. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 34 of 89 
CONFIDENTIAL 
 
 
6.4 
TREATMENT OF PATIENTS 
 
6.4.1 Treatments Administered 
 
For induction therapy, all patients will receive standard idarubicin + cytarabine 
chemotherapy. Patients randomized to Groups 2 and 3 will also receive CX-01. CX-01 
will be continually infused while idarubicin will be administered per institutional 
standard. 
 
Group 1: Idarubicin + Cytarabine 
 
• Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV injection/infusion daily 
on Days 1, 2, and 3 
 
• Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on Days 1-7. 
Group 2: Idarubicin + Cytarabine + plus lower dose CX-01 
 
• CX-01 given as a 4 mg/kg initial bolus on Day 1 only, 30 minutes after 
completion of administration of the first dose of idarubicin, followed by CX-01 
0.125 mg/kg/hour as a continuous 24-hour IV infusion on Days 1-7 
 
• Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV injection/infusion daily 
on Days 1, 2, and 3 
 
• Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on Days 1-7. 
Group 3: Idarubicin + Cytarabine + plus higher dose CX-01 
 
• CX-01 given as a 4 mg/kg initial bolus on Day 1 only, 30 minutes after 
completion of administration of the first dose of idarubicin, followed by CX-01 
0.25 mg/kg/hour as a continuous 24-hour IV infusion on Days 1-7 
 
• Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV injection/infusion daily 
on Days 1, 2, and 3 
 
• Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on Days 1-7. 
Re-induction Therapy 
A bone marrow aspirate and biopsy will be performed between Days 14-21 of the 
induction cycle. If bone marrow shows leukemia-free state, i.e. less than 5% blasts in a 
aspirate sample, no further chemotherapy will be given until recovery of blood counts. If 
the bone marrow shows more than 5% blasts, a re-induction cycle may be given as 
outlined above. If the Days 14-21 marrow is indeterminate e.g., if there is a question of 
residual leukemia, a bone marrow aspirate may be repeated 7 days later for confirmation. 
Re-induction will be given with the same assigned regimen (“7 + 3” ± CX-01) as 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 35 of 89 
CONFIDENTIAL 
 
 
administered during the first induction cycle as outlined above. 
 
If in the Investigator’s opinion, the patient is not fit to receive full re-induction cycle of 
“7 + 3” ± CX-01 at the Investigator’s discretion the patient may receive “5 + 2” ± CX-01 
which is 5 days of cytarabine and 2 days of idarubicin as outlined below: 
 
Group 1: Idarubicin + Cytarabine 
 
• Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV injection/infusion daily 
on Days 1 and 2 
 
• Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on Days 1-5. 
Group 2: Idarubicin + Cytarabine + plus lower dose CX-01 
 
• CX-01 given as a 4 mg/kg initial bolus on Day 1, 30 minutes after completion of 
administration of the first dose of idarubicin followed by CX-01 
0.125 mg/kg/hour as a continuous 24-hour IV infusion on Days 1-5 
 
• Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV injection/infusion daily 
on Days 1 and 2 
 
• Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on Days 1-5. 
Group 3: Idarubicin + Cytarabine + plus higher dose CX-01 
 
• CX-01 given as a 4 mg/kg initial bolus on Day 1, 30 minutes after completion of 
administration of the first dose of idarubicin followed by CX-01 0.25 mg/kg/hour 
as a continuous 24-hour IV infusion on Days 1-5 
 
• Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) IV injection/infusion daily 
on Days 1 and 2 
 
• Cytarabine 100 mg/m2/day by continuous 24-hour IV infusion on Days 1-5. 
Consolidation Therapy 
Evaluation for remission will take place at the time of count recovery, or, if no count 
recovery is achieved, at approximately Day 35 if the patient received one induction 
course or approximately Day 49 if the patient received re-induction course. Count 
recovery is defined as ANC >1,000/μL and platelet count of >100,000/μL. Remission 
will be defined according to IWG criteria (Appendix A). For patients with documented 
CR, confirmatory bone marrow aspirate slides will be submitted to the Sponsor or 
designee. 


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CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 36 of 89 
CONFIDENTIAL 
 
 
Patients in remission at the end of induction may proceed to consolidation therapy on 
study, depending upon factors including, but not limited to, European Leukemia Net 
(ELN) (70) genetic risk and co-existing conditions. 
 
Patients who are not in CR at the end of re-induction will be taken off study and will 
complete Early Termination Visit as per Table 6—1. 
 
Patients who could benefit from and are eligible to undergo stem cell transplantation will 
go off the study at any time when transplant is feasible. 
 
Patients will receive up to two cycles of consolidation therapy on study, per NCCN 
guidelines, depending upon factors including, but not limited to, ELN genetic risk and co- 
existing conditions. A cycle of consolidation therapy is defined as the time from initiation 
of chemotherapy on Day 1 until count recovery. 
 
Patients may start consolidation therapy anywhere from 4 to 8 weeks after the start of 
induction therapy based on treating Investigator judgment. Consolidation will begin no 
sooner than 28 days from the start of induction therapy. 
 
Subsequent consolidation cycles may begin anywhere from 4 to 8 weeks after the start of 
the last cycle of consolidation based on treating Investigator judgment. 
 
Patients will receive consolidation therapy in the same treatment group as assigned at 
randomization, as follows: 
 
Group 1: Cytarabine 
 
• Cytarabine 1.0 gram/m2 over 3 hours, every 12 hours on Days 1, 3, and 5. 
Group 2: Cytarabine + lower dose CX-01 
 
• CX-01 given as a 4 mg/kg initial bolus on Day 1, 30 minutes after completion of 
the first 3-hour infusion of cytarabine, followed immediately by CX-01 
0.125 mg/kg/hour as a continuous 24-hour IV infusion on Days 1-5 for a total of 
120 hours of continuous CX-01 infusion 
 
• Cytarabine 1.0 gram/m2 over 3 hours, every 12 hours on Days 1, 3, and 5. 
Group 3: Cytarabine + higher dose CX-01 
 
• CX-01 given as a 4 mg/kg initial bolus on Day 1, 30 minutes after completion of 
the first 3-hour infusion of cytarabine, followed immediately by CX-01 
0.25 mg/kg/hour as a continuous 24-hour IV infusion on Days 1-5 for a total of 
120 hours of continuous CX-01 infusion 
 
• Cytarabine 1.0 gram/m2 over 3 hours, every 12 hours on Days 1, 3, and 5. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 37 of 89 
CONFIDENTIAL 
 
 
6.4.1.1 
Transfusions 
 
• Red blood cell (RBC) transfusion will be administered according to institutional 
guidelines 
 
• Platelet transfusions will also be given at the discretion of the treating Investigator 
based on clinical characteristics and patient need. 
 
6.4.1.2 
Dosing and Method of Administration 
 
All chemotherapy and CX-01 doses will be calculated based on actual body weight at the 
beginning of each cycle of induction or consolidation therapy. 
 
Chemotherapy will be administered through a central venous catheter, such as a 
peripherally inserted central catheter, with two or three independent ports. This catheter 
may also be used for administration of blood products, IV medications and IV fluids. 
 
CX-01 bolus and continuous infusions may be administered in the same arm through a 
peripheral IV line; however, must be separate from the central line or port used for 
chemotherapy. 
 
6.4.1.3 
Preparation of CX-01 Infusion 
 
The Investigator and pharmacist at the investigational site will ensure Good Pharmacy 
Practices are followed during the preparation of the CX-01 IV solution. The volumes and 
CX-01 concentration in the final CX-01 IV solutions must be verified to be correct based 
on the patient’s actual body weight measured at the beginning of the cycle. 
 
6.4.1.4 
Preparation of CX-01 Intravenous Bolus Dose 
 
The pharmacist will prepare the IV bolus resulting from the 4 mg/kg dose calculation 
with the amount of CX-01 from the appropriate number of 10 mL vials. Each 1 mL 
solution contains 50 mg CX-01 and must be further diluted in 0.9% sodium chloride. This 
calculated volume per patient (based on weight) will be added to 30 mL of 0.9% sodium 
chloride solution and the total volume administered IV over 5 minutes. 
 
6.4.1.5 
Preparation of CX-01 Continuous Infusion Dose 
 
The pharmacist will prepare each study treatment solution, adding the calculated amounts 
of CX-01 and 0.9% sodium chloride to an empty, sterile infusion bag. An IV infusion line 
will then be attached to the infusion bag, and the infusion set purged with the CX-01 
solution. A Luer lock (or similar) will then be placed at the end of the set. As CX-01 
doses are weight based, the amount of CX-01 from the vials and saline solution will both 
vary by patient’s weight. Each 1 mL solution contains 50 mg CX-01. 
 
For each continuous infusion bag, an appropriate volume and concentration of CX-01 
solution will be prepared such that the patient receives a continuous infusion at the dose 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 38 of 89 
CONFIDENTIAL 
 
 
of CX-01 assigned at randomization, 0.125 or 0.25 mg/kg/hour. The final volume of the 
CX-01 infusion will be 500 to 1000 mL/24 hours. The infusion bags will be prepared at a 
calculated CX-01 concentration based on the patient’s actual body weight. 
 
Based upon current stability testing data, CX-01 infusion solutions will expire at room 
temperature 72 hours after preparation and should be stored in a refrigerator (2 to 8ºC) 
until used. 
 
If the IV infusion is interrupted for any reason, the time of infusion stop will be recorded, 
along with the reason. The IV infusion will be restarted as soon as possible, and the 
restart time recorded. The planned cycle days of treatment administration will not be 
altered, nor will the concentration of the CX-01 solution be adjusted, to compensate for 
an interrupted CX-01 infusion. 
 
6.4.2 Investigational Product 
 
CX-01 (2-O, 3-O desulfated heparin [ODSH]) is an off-white to pinkish amorphous 
powder. CX-01 is a low anticoagulant, anti-inflammatory UFH derivative produced for 
human use compliant with current Good Manufacturing Practices (cGMP). The structural 
formula for the basic repeating unit that comprises CX-01 is provided in Figure 6—2. 
 
Figure 6—2 Structure of CX-01 
 
Further details are provided in the IB (63). 
 
6.4.2.1 
Packaging and Labeling 
 
Idarubicin and cytarabine will be obtained from commercial sources. These treatments 
will be prepared by the investigational site pharmacy using standard institutional 
procedures according to the respective package insert for each agent. 
 
Adequate supplies of the study drug, CX-01, will be provided to each investigational site. 
The study drug (CX-01) was manufactured under cGMP and will be supplied by Sponsor 
and packaged in 10 mL sterile, single -use glass vials. The 10 mL vial contains 500 mg 
total CX-01 (50 mg per mL). 
 
Each vial will be labeled in English and in accordance with United States (US) 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 39 of 89 
CONFIDENTIAL 
 
 
requirements since all investigational sites participating in the study will be in US. Label 
text will be approved according to the Sponsor’s agreed procedures. The lot numbers and 
expiration dates of the batches of CX-01 vials used in this study will be printed on the 
vial labels. 
 
For all vials, a system in accordance with cGMP will be used; ensuring each dose of 
study drug can be traced back to the respective bulk ware of the ingredients. A complete 
record of batch numbers and expiry dates of all study drug and labels will be maintained 
in the Sponsor’s study file. 
 
6.4.2.2 
Storage and Stability 
 
The study medication must be stored in a secure limited access area according to local 
regulations. CX-01 vials should be stored at room temperature, preferably between 5ºC 
and 25ºC (41 F to 77ºF). 
 
Long term stability testing for active pharmaceutical ingredient (API) and final product 
(CX-01 vials) was conducted in compliance with FDA requirements. Results from these 
stability studies indicate that CX-01 API and CX-01product are stable for at least 
48 months when stored at room temperature. The API and final product studies are being 
conducted with current production material to confirm prior results and extend the study 
period to 72 months. A stability study of CX-01 in normal saline diluted for bolus dose 
concentration and continuous infusion concentration (in polyethylene bags) has 
confirmed stability of the drug product for at least 72 hours (the maximum period tested) 
at two concentration levels and at two temperature conditions (2ºC to 8ºC and room 
temperature). This testing covers all the ranges for CX-01 concentration/dilution required 
when dosing for clinical trials. 
 
Since CX-01 vials are photo-stable, there is no need to protect from direct or indirect 
light. 
 
6.4.2.3 
Study Drug Accountability, Reconciliation, and Return 
 
Upon completion and termination of the study, all unused and/or partially used study 
drug must be returned to the Sponsor, or other authorized party if not authorized by the 
Sponsor to be destroyed at the site. 
 
All study drugs returned to the Sponsor or other authorized party must be accompanied 
by the appropriate documentation and be clearly identified. Study drug may only be 
returned after drug accountability is completed. Returned supplies should be in their 
original containers (vials that have clinical labels attached). Empty vials should not be 
returned to the Sponsor. Empty vials may not be destroyed until drug accountability is 
completed. It is the Investigator’s responsibility to arrange disposal of all empty vials 
according to institutional regulations. The return or destruction of unused study drug 
should be arranged by the site Monitor. 


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CONFIDENTIAL 
 
 
6.4.2.4 
Study Drug Handling and Disposal 
 
The Sponsor will be responsible for assuring that the quality of the study drug is adequate 
for the duration of the study. It is the responsibility of the Investigator or designee to 
ensure that the study drug is only dispensed to the patient. The study drug must be 
dispensed only from official study sites by authorized personnel according to local 
regulations. The Investigator or designee must maintain accurate records of the study 
drug receipt, dispensing information, and disposition. 
 
If study drug is to be destroyed at the site, it is the Investigator or designee’s 
responsibility to ensure that arrangements have been made for the disposal, drug 
accountability has been completed by the site Monitor, procedures for proper disposal 
have been established according to applicable regulations, guidelines and institutional 
procedures, and appropriate records of the disposal have been documented and provided 
to the Sponsor or designee. 
 
6.4.3 Method of Assigning Patients to CX-01 
 
6.4.3.1 
Patient Identification 
 
Each newly enrolled patient will be assigned a unique patient identification number using 
an Interactive Web/Voice Response System (IxRS). Patients will be randomized across 
all sites. Patients who discontinue from the study will not be replaced. 
 
6.4.4 Selection of Doses in the Study 
 
6.4.4.1 
Selection of Dose 
 
The selection of CX-01 dose for study in AML has been based upon the dual 
requirements to have sufficient drug administered to have potential activity but without 
clinically significant anticoagulation. The study dose chosen (4 mg/kg bolus followed by 
0.125 or 0.25 mg/kg/hour for 5 or 7 days) fulfills both of these criteria. In addition, all 
doses are expected to result in serum levels of CX-01 which are significantly higher than 
the IC90 identified in preclinical studies for inhibition of CXCL12-CXCR4 interaction. 
 
In a pilot study of CX-01 conducted on 12 patients with newly diagnosed AML, the 
addition of CX-01 to the traditional “7 + 3” regimen of cytarabine and idarubicin resulted 
in 11 of 12 patients achieving complete bone marrow remission after the first cycle 
(92%). It was hypothesized that the increased rate of first cycle induction of remission 
was from blockade by CX-01 of CXCL12 (SDF-1)/CXCR4-mediated homing of LSC in 
the marrow niche where they are protected from chemotherapy. The dose and regimen of 
CX-01 in that trial were well tolerated without associated serious AEs (SAEs). Mean 
levels of aPTT remained largely in the mid-30 second range. 
 
In a prior study of continually infused CX-01 in patients with metastatic pancreatic 
cancer (Study PGX-ODSH-2011-PC), CX-01 was administered as an IV bolus loading 
dose of 4 mg/kg, followed by a continuous infusion of 0.375 mg/kg/hour for 5 days. This 


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dose was well tolerated and free from major AEs. However, measurement of aPTT in 
these patients demonstrated that aPTT was increased into the 40 to 45 second range in a 
limited number of patients. This is a range that is not overtly anticoagulant, but higher 
than the therapeutic range of aPTT (31.5 to 36 seconds). 
 
Therefore, the chosen dose (4 mg/kg bolus followed by 0.125 or 0.25 mg/kg/hour) 
represents a rational balance between effective dosing and safety in seriously ill patients 
with AML. 
 
6.4.4.2 
Dose Modifications 
 
No dose modification for cytarabine or idarubicin during induction will be allowed. 
However, dose reduction of cytarabine during consolidation is permitted according to 
institutional guidelines, or if in the Investigator’s opinion the patient cannot tolerate a 
higher dose. 
 
CX-01 Dose Modifications 
 
• CX-01 will be temporarily discontinued in patients who develop aPTT above 
45 seconds during continuous infusion of CX-01 and at least 8 hours after the 
bolus dose of CX-01, until the aPTT is <35 seconds. CX-01 will then be resumed 
at a 50% dose reduction. If the aPTT rises above 45 seconds at the reduced dose, 
CX-01 will be permanently discontinued. If aPTT at the 50% reduced dose is 
<35 seconds, 4 hours or more after dose reduction, the dose can be escalated by 
25%. If the aPTT after dose escalation again rises above 45 seconds at the 
reduced dose, the CX-01 will be temporarily discontinued until the aPTT is 
<35 seconds, and then resumed at the previous 50% dose reduction. 
 
• Abnormal liver function: 
o If Grade 1 increases in AST, ALT, or bilirubin occur (e.g., increase in 
AST or ALT from ULN to 3.0 x ULN; increase in total bilirubin from 
ULN to 1.5 x ULN), the frequency of liver function testing will be 
increased, if the Investigator judges that the laboratory abnormalities are 
potentially related to study treatment. No reduction of dose is required 
 
o If Grade 2 increases in AST, ALT, or bilirubin occur (e.g., increase in 
AST or ALT to >3.0 to 5 x ULN; increase in total bilirubin from >1.5 to 
3 x ULN), the frequency of liver function testing will be increased to 
≥once a week, if the Investigator judges that the laboratory abnormalities 
are potentially related to study treatment. No reduction of dose is required 
 
o If Grade 3 increases in AST, ALT, or bilirubin occur (e.g., increase in 
AST or ALT to >5.0 to 20 x ULN; increase in total bilirubin from >3.0 to 
10 x ULN) and if the Investigator judges that the laboratory abnormalities 
are potentially related to study treatment, study drug must be stopped. 
Frequent laboratory evaluations (more than once weekly) will be 


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CONFIDENTIAL 
 
 
conducted until liver function tests return to Grade 1 or baseline value. 
Study treatment will be resumed after liver function tests return to Grade 1 
or baseline value provided administration of chemotherapy is in progress. 
If resumption of study treatment is considered for subjects who have 
experienced Grade 3 increases in AST, ALT, or bilirubin liver function 
will be monitored at least daily during CX-01 infusion 
 
o If Grade 4 increases in AST, ALT, or bilirubin occur (e.g., increase in 
AST or ALT to >20 x ULN; increase in total bilirubin to >10 x ULN) and 
if the Investigator judges that the laboratory abnormalities are potentially 
related to study treatment, the patient must discontinue study treatment 
immediately and will not be re-challenged. The patient will be followed 
until resolution of abnormal liver function tests. 
 
• Renal function: 
If the calculated creatinine clearance drops below 30 mL/min/1.73m2 prior to or 
during dosing with CX-01, the dose of CX-01 will be held until the creatinine 
clearance rises above 30 mL/min/1.73m2. 
• For any other Grade 3 or 4 toxicities that appear to be related to CX-01 during 
either the induction or consolidation cycles, CX-01 will be interrupted until the 
AE resolves to Grade 1 or less, and then resumed at 0.125 mg/kg/hour provided 
administration of chemotherapy is in progress. If CX-01 is interrupted for greater 
than 72 hours, the patient will be discontinued from treatment. If the AE recurs at 
a level of Grade 3 or higher, the CX-01 will be discontinued. 
 
This study will utilize the National Cancer Institute-Common Terminology Criteria for 
Adverse Events (NCI-CTCAE) Version 4.03 for AE and SAE reporting. A copy of the 
CTCAE Version 4.03 can be downloaded: (http://safetyprofiler 
ctep.nci.nih.gov/CTC/CTC.aspx). 
 
6.4.5 Prior and Concomitant Medications 
 
The Investigator must record the use of all concomitant medications taken during 30 days 
prior to signing informed consent and for the duration of the study until the Safety 
Follow-Up Visit, both prescribed and over-the-counter, in the source documents and 
electronic case report form (eCRF). Patients should be discouraged from starting any new 
medication, both prescribed and over-the-counter, without consulting the Investigator 
unless the new medication is required for emergency. 
 
6.4.5.1 
Permitted Concomitant Medications 
 
Refer to Section 6.4.1.1 for transfusion parameters. Treatment for disease-related 
symptoms and drug-related toxicities are expected as standard of care and should be 
recorded in the patient’s medical record and eCRF. 


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The use of myelopoietic growth factors (G-CSF and GM-CSF) is allowed, consistent 
with the Investigator’s clinical judgment and institutional guidelines. 
 
6.4.5.2 
Prohibited Concomitant Medications 
 
Patients are not permitted to take those medications specified in the exclusion criteria 
(Section 6.3.2). 
 
The following medications are prohibited: 
 
• Any anticoagulation therapy (with the exception of heparin flushes). CX-01 IV 
bolus doses may cause a slight transient increase of aPTT (to approximately 
60 seconds) for less than 1 hour, while the continuous IV infusion at the doses to 
be used in this study, based upon previous studies, will raise the aPTT to the ULN 
or to a level (approximately 35 to 45 seconds) that is not of clinical significance. 
CX-01 may, however, potentiate the anticoagulation effect of UFH, LMWH or 
anticoagulants if administered concomitantly. Therefore, concomitant 
administration of CX-01 with other anticoagulants will not be permitted in 
patients participating in this study other than as heparin flushed to maintain IV 
line patency. 
 
• Any investigational therapeutic agents. 
6.4.6 Treatment Compliance 
 
Since all treatments are administered at the clinical site by site personnel, the Investigator 
or designee must maintain accurate records of all study treatments, including dates of 
study drug receipt; quantities received and dispensed, and lot numbers. In addition, the 
study treatment must be noted in the patient’s medical records and eCRF, with the date 
and time of administration and dose of each study treatment. 
 
6.5 
Study Procedures 
 
6.5.1 Schedule of Study Procedures 
 
Table 6—1 presents induction/re-induction cycles and Table 6—2 presents’ consolidation 
cycles. 


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Table 6—1 Induction/Re-induction Cycle Schedule of Study Procedures 
 
 
Examination 
Screen 
Visit 
D 
-28 – 1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D 
8-13 
D 
14-21 
At count 
recovery 
& Weekly 
from D21 
until 
count 
recovery 
or D6015 
Early 
Term 
Visit 
Safety FU 
visit 
(30 days 
after last 
dose of 
treatment) 
Long 
Term FU 
contact 
(every 
3 months 
up to 
death, or 
EoS) 16 
Informed consent1 
X 
Demographic and 
medical history 
X 
Eligibility criteria 
X 
X 
Randomization 
X 
Idarubicin 2 
X 
X 
X 
Cytarabine3 
X 
X 
X 
X 
X 
X 
X 
CX-01 Bolus4 
X 
CX-015 continuous 
infusion 
X 
X 
X 
X 
X 
X 
X 
ECOG status 
X 
Vital signs (BP, heart 
rate, height and 
weight)6 
X 
Physical exam 
X 
12-lead ECG 
X 
X 
Echocardiography or 
MUGA scan 
X 
Hematology7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-factor Xa8,9 
X 
X 
X 
X 
X 
X 
X 
X 
X9 
X 
PT/INR, aPTT8,10 
X 
X 
X 
X 
X 
X 
X 
X 
X10 
X 
X 
X 
X 


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Clinical Study Protocol 
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Table 6—1 Induction/Re-induction Cycle Schedule of Study Procedures 
 
 
Examination 
Screen 
Visit 
D 
-28 – 1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D 
8-13 
D 
14-21 
At count 
recovery 
& Weekly 
from D21 
until 
count 
recovery 
or D6015 
Early 
Term 
Visit 
Safety FU 
visit 
(30 days 
after last 
dose of 
treatment) 
Long 
Term FU 
contact 
(every 
3 months 
up to 
death, or 
EoS) 16 
Chemistry11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK sampling12 
X 
X 
AE Assessment 
Continuously 
Previous medications 
X 
Concomitant 
medications 
continuously 
Fibrinogen, D-dimer 
X 
X 
X 
X 
Serum or urine 
pregnancy test13 
X 
X 
Bone marrow 
aspirate/ 
Biopsy14 
X14 
X14 
X14 
Relapse and survival 
data 
X 
Abbreviations: AE=adverse event, ALT=alanine aminotransferase, ANC=absolute neutrophil count, anti-Xa=anti-factor 10a, aPTT=activated partial 
thromboplastin time, AST=aspartate aminotransferase, BP=blood pressure, BUN=blood urea nitrogen, CBC=complete blood count, CX-01=2-O, 3-O desulfated 
heparin, D=day, ECG=electrocardiogram, ECOG=Eastern Cooperative Oncology Group, EoS=end of study, FU=follow-up, INR=international normalized ratio, 
IV=intravenous, LDH=lactate dehydrogenase, MUGA=multi gated acquisition, OS=overall survival, PK=pharmacokinetics, PT=prothrombin time, 
Term=termination. 
 
1. Informed consent must be obtained before any study-related procedures are conducted. 


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2. Idarubicin administered at a dose of 12 mg/m2/day by slow (10 to 30 minutes) IV injection/infusion daily on Days 1, 2, and 3. 
3. Cytarabine administered at a dose of 100 mg/m2/day as a continuous 24-hour IV infusion on Days 1-7. Patients who do not achieve leukemia-free state 
(<5% bone marrow blasts) on bone marrow aspirate performed between Days 14-21 may receive a re-induction cycle with the same regimen (“7 + 3” ± 
CX-01). If in the Investigator’s opinion, the patient is not fit to receive full re-induction cycle of “7 + 3” ± CX-01, at the Investigator’s discretion the 
patient may receive “5 + 2” ± CX-01 which is 5 days of cytarabine (Days 1-5) and 2 days of idarubicin (Days 1 and 2). 
4. CX-01 administered at a dose of 4 mg/kg as an initial bolus on Day 1 only, 30 minutes after completion of administration of the first dose of idarubicin. 
5. CX-01 administered at a dose of 0.125 or 0.25 mg/kg/hour as a continuous 24-hour IV infusion on Days 1-7. 
6. Height obtained at Screening only. Actual body weight will be measured at the beginning of each cycle to calculate treatment doses. 
7. Hematology must include the following: hemoglobin, ANC, and platelets. All other hematology assessments should be performed only if standard of care 
and/or clinically indicated. Hematology samples will be collected daily until discharge and weekly thereafter until recovery. 
8. Note: blood samples for PT/INR, aPTT and anti-Xa levels will be collected 12 hours after the bolus dose of CX-01. 
9. Anti-Xa samples will be collected only on Days 1-8. 
10. PT/aPTT will be collected daily on Days 1-8, and on Day 9, Day 11, and Day 13. 
11. Chemistry (and comprehensive metabolic panel) includes BUN, serum creatinine, total bilirubin, ALT, AST, and alkaline phosphatase. Samples will be 
collected daily until discharge. 
12. At selected sites, blood samples for steady-state PK analysis will be collected during the induction cycle from the first six randomized patients assigned 
to CX-01 on Days 3 and 5 at a single time point. 
13. For females of childbearing potential only. All female patients will have a urine pregnancy test at Screening; positive urine tests must be confirmed by a 
serum pregnancy test. 
14. Bone marrow aspirates and/or biopsies are not performed weekly. If the patient’s peripheral blood is negative for persistent AML: a bone marrow aspirate 
and/or biopsy will be performed (once) between Days 14-21 to determine the need for re-induction. Bone marrow biopsy may be necessary if sufficient 
spicules are not available on aspirate. Bone marrow aspirate at baseline and follow-up should include analysis by flow cytometry and cytogenetic analysis. 
Bone marrow (or peripheral blood if bone marrow is unavailable) should be sent to the institution’s local cytogenetic laboratory for analysis. For patients 
with documented CR, confirmatory bone marrow aspirate slides will be submitted to the Sponsor or designee. If count recovery has not occurred by Day 
42, a bone marrow aspirate/biopsy will be performed to evaluate disease status, unless presence of persistent AML in peripheral blood. 
15. Count recovery is defined as ANC of >1000/μL and a platelet count >100,000/μL. 
16. During long term follow-up, relapse and survival data will be collected every 3 months until death or until the end of study. The end of study will occur 
approximately 18 months after the last patient is randomized. 


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Table 6—2 Consolidation Cycle Schedule of Study Procedures 
 
Examination 
D 
1 
D 
2 
D 
3 
D 
4 
D 
5 
Weekly 
from D6 
until 
count 
recovery8 
Hematology1 
X 
X 
X 
X 
X 
X 
PT/INR, 
aPTT, and 
anti-Xa2 
X 
X 
X 
X 
X 
Chemistry3 
X 
X 
X 
X 
X 
X 
Vital signs 
(BP, heart 
rate, height 
and weight)4 
X 
Cytarabine5 
X 
X 
X 
CX-01 
Bolus6 
X 
CX-017 
continuous 
infusion 
X 
X 
X 
X 
X 
Concomitant 
medications 
continuously 
Adverse 
events 
continuously 
Bone 
marrow 
aspirate/ 
Biopsy 
X9 
 
Abbreviations: aPTT=activated partial thromboplastin time, anti-Xa=anti-factor 10a, BP=blood pressure; CBC=complete blood count, D=day, 
INR=international normalized ratio, PT=prothrombin time. 
1. Hematology must include the following: hemoglobin, ANC, and platelets. All other hematology assessments should be performed only if standard of 
care and/or clinically indicated. Hematology samples will be collected daily until discharge and weekly thereafter until recovery. 


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2. PT/aPTT and anti-Xa blood samples will be collected 12 hours after the bolus dose of CX-01. 
3. Chemistry (and comprehensive metabolic panel) will be collected daily until discharge. 
4. Actual body weight will be measured at the beginning of each cycle to calculate treatment doses. 
5. Cytarabine administered at a dose of 1.0 g/m2 over 3 hours, every 12 hours on Days 1, 3, and 5. 
6. CX-01 administered at a dose of 4 mg/kg as an initial bolus on Day 1, 30 minutes after completion of the first 3-hour infusion of cytarabine, followed 
immediately by a continuous CX-01 24-hour IV infusion. 
7. CX-01 administered at a dose of 0.125 or 0.25 mg/kg/hour as a continuous 24-hour IV infusion on Days 1-5 for a total of 120 hours of continuous CX-01 
infusion. 
8. Count recovery is defined as ANC of >1000/μL and a platelet count >100,000/μL. 
9. Bone marrow aspirate/biopsy is not done weekly. If the patient’s peripheral blood is negative for persistent AML and count recovery has not occurred 
by Day 42 (of Consolidation cycle), a bone marrow aspirate/biopsy will be done to evaluate disease status. 


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6.5.2 Screening Procedures 
 
Eligibility will be assessed at the Screening Visit. Informed consent will be obtained at 
the Screening Visit, prior to performing any study-related procedures. All inclusion 
criteria must be met and all exclusion criteria must be absent for the patient to qualify for 
enrollment in the study. The Screening period may last no more than 28 days before the 
patient is randomized in the study. 
 
The following will be conducted and all results will be documented during Screening: 
 
• Informed consent 
• Demographics and medical history 
• Eligibility criteria assessment according to inclusion/exclusion criteria 
• ECOG performance status 
• Vital signs (including heart rate, blood pressure [BP], height, and weight) 
• Physical exam 
• 12-lead electrocardiogram (ECG) 
• Echocardiography or MUGA scan for cardiac ejection fraction 
• Clinical laboratory assessments (serum chemistry, hematology, and coagulation 
testing). All Screening laboratory tests will be performed locally 
 
• Fibrinogen, D-dimer 
• Assessment of AEs 
• Assessment of previous and concomitant medications (including anti-cancer 
medications). All concomitant medications and medications taken within 30 days 
prior to informed consent must be documented 
 
• Urine pregnancy test will be performed for all female patients of childbearing 
potential; positive urine tests will be confirmed by a serum pregnancy test 
 
• Bone marrow aspirate/biopsy. 
6.5.3 Randomization 
 
Randomization will occur after eligibility is confirmed for consenting study participants. 
Study drug will be administered following randomization. 


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6.5.4 Treatment Procedures 
Induction/re-induction cycle 
• Administration of standard chemotherapy; idarubicin on Days 1-3 and cytarabine 
on Days 1-7 
 
• Administration of CX-01 as an initial bolus on Day 1 only 
• Administration of CX-01 as a continuous infusion on Days 1-7 
(Note: if a patient is not fit to receive the full re-induction cycle of “7 + 3” ± 
CX-01, at the Investigator’s discretion the patient may receive “5 + 2” ± CX-01 
which is 5 days of cytarabine [Days 1-5] and 2 days of idarubicin [Days 1 and 2]). 
 
• 12-lead ECG on Day 7 
• Clinical laboratory assessments 
• Assessment of AEs 
• Assessment of concomitant medications 
• PK sampling on Days 3 and 5 (performed at selected sites and collected during 
the induction cycle from the first six randomized patients assigned to CX-01). 
 
Consolidation cycle 
 
• Administration of cytarabine on Days 1, 3, and 5 
• Administration of CX-01 as an initial bolus on Day 1 
• Administration of CX-01 as a continuous infusion on Days 1-5 
• Clinical laboratory assessments 
• Assessment of AEs 
• Assessment of concomitant medications. 
6.5.5 Safety Follow-Up Visit 
 
Patients will complete a Safety Follow-Up Visit approximately 30 days after completion 
of the last induction or consolidation cycle. See Table 6—1 for clinical assessments 
performed at this visit. Longer follow-up may be required for patients who do not have an 
ANC recovery by Day 42 (that is, until the recovery or until a reason for no recovery is 
diagnosed) after the last induction or consolidation cycle. 


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6.5.6 Early Term Visit 
 
In case of early termination, the following will be conducted (see Table 6—1 for details) 
and all results will be documented: 
 
• Hematology 
• PT/INR, aPTT, and anti-factor Xa 
• Chemistry 
• AE Assessment 
• Concomitant medications 
• Fibrinogen, D dimer 
6.5.7 Long Term Follow-Up 
 
After Safety Follow-Up Visit, the relapse and survival data will be collected every 
3 months. 
 
Each subject will participate in the long term follow-up for approximately 18 months 
from the time of informed consent until death or until the end of the study (for the 
definition of end of study, see Section 6.1). 
 
Investigational sites are expected to make every effort to obtain long term follow-up data. 
This level of diligence is necessary to ascertain the patient’s health status, and thus avoid 
lost to follow-up status for efficacy assessments. Follow-up may require: 
 
• Permission for study personnel to contact an alternative person (e.g., family, 
spouse, partner, legal representative, or physician) even if only by telephone 
 
• Permission for study personnel to access and review the patient’s medical 
information from alternative resources (e.g., doctors notes, hospital records) 
 
Attempts to contact patients must be documented in the patient’s source documents and 
in the eCRF. The source documents for OS may be sent remotely to the site Clinical 
Research Associate for review and verification (ensuring patient identifiers are redacted 
except for study number and initials). 
 
6.6 
EFFICACY AND SAFETY VARIABLES 
 
6.6.1 Appropriateness of Measurements 
 
The safety and efficacy measurements used in the evaluation of the study endpoints are 
widely used and recognized as reliable, accurate, and conform to standard of care. 


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Response will be evaluated according to IWG criteria (see Appendix A), which has been 
published and validated and is appropriate for use in this study. 
 
6.6.2 Efficacy Assessments 
 
6.6.2.1 
Primary Efficacy Assessment 
 
The primary endpoint is the rate of patients in each treatment group achieving 
morphological CR based on IWG criteria during the induction and re-induction phases of 
the treatment. Morphologic CR is defined as ANC >1000/μL, platelet 
count >100,000/μL, <5% blasts in an bone marrow aspirate sample, no blasts with Auer 
rods, and no evidence of extramedullary disease (see Appendix A). 
 
6.6.2.2 
Secondary Efficacy Assessments 
 
6.6.2.2.1 
Event-Free Survival 
 
Event-free survival is measured from the date of randomization until treatment failure 
(e.g., failure to achieve composite complete morphological remission during the 
induction or re-induction phase of the study lasting up to 60 days, relapse from CR, or 
death from any cause, whichever occurs first). 
 
6.6.2.2.2 
Leukemia-Free Survival 
 
Leukemia-free survival is only assessed in patients who achieve composite CR and is 
measured from the date of randomization until disease relapse or patient death from any 
cause, whichever occurs first. 
 
6.6.2.2.3 
Overall Survival 
 
Overall survival is measured from the date of randomization until death from any cause. 
 
6.6.2.2.4 
Composite Complete Remission Rate 
 
Complete remission rate includes CR, CR without recovery of platelets (CRp) and CRi as 
defined by IWG criteria (Appendix A) during the induction and re-induction phases of 
treatment. 
 
6.6.2.2.5 
Duration of Morphologic Complete Remission 
 
Duration of morphologic complete response is measured from the achievement of CR to 
detection of relapse. 
 
6.6.2.2.6 
30-Day, 60-Day and 90-Day Mortality 
 
Thirty-day, 60-day, and 90-day mortality are the rate of death during 30 days, 60 days, 
and 90 days, respectively, from the first day of induction treatment. 


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CONFIDENTIAL 
 
 
6.6.2.2.7 
Neutrophil and Platelet Recovery 
 
Time to neutrophil recovery is measured from the date of randomization until ANC 
recovers to >1000/μL. 
 
Time to transfusion-independent platelet recovery is measured from the date of 
randomization until the first day that the platelet count recovers to >100,000/μL 
(provided it is not as a consequence of platelet transfusion and provided platelets are then 
maintained at >100,000/μL for the five subsequent days without platelet transfusion). 
 
6.6.3 Safety Assessments 
 
Key safety endpoints will be assessed by review of summaries of AEs which will include 
only treatment-emergent AEs (TEAEs), unless otherwise stated. Adverse events will be 
categorized by System Organ Class (SOC) and preferred term using the Medical 
Dictionary for Regulatory Activities (MedDRA) dictionary (version 14.1), and will be 
graded according to NCI-CTCAE version 4.03. 
 
6.6.3.1 
Adverse Events 
 
Adverse events will be monitored throughout the study. Adverse events will be collected 
from the time of informed consent and continue until 30 days after the last study 
treatment is administered. Longer follow-up and collection of AEs may be required for 
patients who do not have an ANC recovery by Day 42 (i.e., until the recovery or until a 
reason for no recovery is diagnosed) after the last induction or consolidation cycle. 
 
For the purpose of this study, the terms toxicity and AE are used interchangeably. 
 
6.6.3.2 
Definitions 
 
6.6.3.2.1 
Definition of an Adverse Event 
 
In a clinical study, an AE is any untoward medical occurrence (i.e., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom, or disease) in a 
patient or clinical investigation subject after providing written informed consent for 
participation in the study. Therefore, an AE may or may not be temporally or casually 
associated with the use of a medicinal (investigational) product. 
 
A surgical procedure that was planned prior to the start of the study by any physician 
treating the subject should not be recorded as an AE (however, the condition for which 
the surgery is required may be an AE). 
 
In the following differentiation between medical history and AEs the term “condition” 
may include abnormal symptoms, diseases, laboratory, or vital sign findings. 
 
• Conditions that started before signing of ICF and for which no symptoms or 
treatment are present until signing of ICF are recorded as medical history (e.g., 


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seasonal allergy without acute complaints) 
 
• Conditions that started before signing of ICF and for which symptoms or 
treatment are present after signing of ICF, at unchanged frequency and/or 
intensity, are recorded as medical history (e.g., allergic pollinosis) 
 
• Conditions that started or deteriorated after signing of informed consent will be 
documented as AEs. 
 
 
Abnormal laboratory and other abnormal investigational findings (i.e., physical exam) 
should not be reported as AEs unless they are associated with clinical signs and 
symptoms, lead to treatment discontinuation or are otherwise considered clinically 
relevant by the Investigator. In cases of surgical or diagnostic procedures, the 
condition/illness leading to such a procedure is considered as the AE rather than the 
procedure itself. In a case of fatality, the cause of death is considered as the AE, and the 
death is considered as its outcome. 
 
Medical conditions/diseases present before starting study drug are considered to be an AE 
only if they worsen after starting study drug and are clearly not related to cytarabine 
and/or idarubicin toxicities, or to AML that is not yet in remission. Abnormal laboratory 
values or test results constitute AEs only if they induce clinical signs and symptoms, are 
considered clinically significant, or require therapy. 
 
Information about all AEs, whether volunteered by the patient, discovered by the 
Investigator or designee questioning, or detected through physical examination, 
laboratory test or other means, will be collected and recorded, as appropriate. 
 
As far as possible, each AE should be evaluated to determine: 
 
• The severity grade based on NCI-CTCAE version 4.03 (Grade 1 to 5) 
• The relationship to the study drug(s) (see Section 6.6.3.2.6). A relationship 
between the AE and the underlying AML, the dose-intensive chemotherapy, and 
CX-01 treatment, will be assessed 
 
• The duration (start and end dates or continuing at final contact) 
• Action taken (no action taken, study drug dosage adjusted/temporarily 
interrupted, study drug permanently discontinued due to this AE, concomitant 
medication taken, non-drug therapy given, hospitalization/prolonged 
hospitalization, see Section 6.6.3.2.7) 
 
• Whether it constitutes an SAE. 
All AEs will be treated appropriately. Such treatment may include changes in study drug 


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treatment as listed in the dose modification section of the protocol (Section 6.4.4.2). 
Adverse events will be followed until resolution or stabilization of the event, completion 
of the patient’s participation, or study termination, or the Investigator or designee and 
Sponsor agree that follow-up is no longer necessary, whichever occurs first. 
 
Assessments should be made at each visit (or more frequently, if necessary) of any 
changes in severity, the relationship to the study drug, the intervention required to treat it, 
and the outcome. 
 
Common side effects known for CX-01 are provided in the IB (63). All AEs will be 
immediately recorded in the patient’s source documents. 
 
6.6.3.2.2 
Definition of an Serious Adverse Event 
 
An SAE is defined as any untoward medical occurrence that at any dose either: 
 
• Results in death 
• Is life-threatening 
• Requires patient hospitalization or prolongation of an existing hospitalization. 
Note: Hospitalization for the purpose of administration of induction or 
consolidation treatment will not be considered an AE 
 
• Results in a persistent or significant disability or incapacity (disability is defined 
as a substantial disruption of a person’s ability to conduct normal life function) 
 
• Is congenital anomaly or birth defect 
• Is another medically important serious event as judged by the Investigator. 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which 
the patient 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. 
 
Hospitalization is defined as the patient being hospitalized overnight, or the patient’s 
hospital stay being prolonged for at least an additional overnight stay. Hospitalizations 
for safety reasons, e.g., an overnight stay to avoid a repeat journey, or patients 
undergoing a preplanned hospital procedure, will not be considered an SAE. 
Hospitalizations or prolongation of hospitalization for a procedure will be noted in the 
eCRF. Hospitalization for the purpose of administration of induction or consolidation 
treatment will not be considered an AE. 
 
Important medical events that may result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 


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Examples of such medical events included allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug abuse. 
 
Instances of death or congenital abnormality, if brought to the attention of the 
Investigator at any time after cessation of the study treatment and considered by the 
Investigator to be possibly related to the study treatment, will be reported to the client. 
 
Medical and scientific judgment should be exercised in deciding whether an AE should 
be reported as an SAE in other situations, such as important medical events that may not 
be immediately life-threatening or result in death or hospitalization but may jeopardize 
the patient and may require intervention to prevent one of the other outcomes listed in the 
definition above. 
 
Any AE leading to death from any cause while a patient is receiving treatment on this 
protocol or up to 30 days after the last dose of study treatment which is felt to be related 
to the study drug must be reported as an SAE. 
 
Toxicities which fall within the SAE definitions listed above must be reported as an SAE 
regardless if they are felt to be treatment related or not, with the exception of 
hospitalization for induction, re-induction or consolidation treatment for AML. Toxicities 
unrelated to treatment that do NOT fall within the SAE definitions above, must be 
documented as AEs in the patient’s source documents and eCRF. 
 
6.6.3.2.3 
Suspected Unexpected Serious Adverse Reactions 
 
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not 
listed in the IB. Suspected adverse reactions means any AE for which there is a 
reasonable possibility that the drug caused the AE. For the purposes of Investigational 
New Drug (IND) safety reporting, ‘reasonable possibility’ means there is evidence to 
suggest a causal relationship between the drug and the AE. 
 
6.6.3.2.4 
Follow-up of Adverse Events/Serious Adverse Events 
 
Adverse events will be followed until resolution or stabilization of the event, completion 
of the patient’s participation, or study termination, or the Investigator or designee and 
Sponsor agree that follow-up is no longer necessary, whichever occurs first. 
 
Serious AEs will be followed until resolution, the condition stabilizes, or the Investigator 
or designee and Sponsor agree that follow-up is no longer necessary. 
 
All AEs will be immediately recorded in the patient’s source documents. 
 
6.6.3.2.5 
Assessment of Severity 
 
The severity grade will be based on the NCI-CTCAE version 4.03. An electronic copy of 
the CTCAE Version 4 can be downloaded from: http://safetyprofiler- 


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ctep.nci.nih.gov/CTC/CTC.aspx. 
 
6.6.3.2.6 
Causality Assessment 
 
The Investigator must assess and document causal relationship between an SAE and the 
study drug on the basis of his/her clinical judgment using the following definitions. The 
causality assessment must be made based on the available information and can be 
updated as new information becomes available. 
 
Is there a “reasonable possibility” the drug caused the AE (meaning there is evidence to 
suggest a causal relationship between the drug and the AE)? 
 
• Yes 
• No. 
Could the AE be explained by underlying disease or other drugs or chemicals? 
 
• Yes 
• No. 
6.6.3.2.7 
Action Taken Regarding the Study Drug 
 
• No action taken: no change in treatment dosage 
• Dose reduction: study drug dosage adjusted/or and reduced 
• Drug interrupted: study drug temporarily stopped 
• Drug withdrawn: study drug permanently stopped 
• Specific treatment instituted: other concomitant medication or non-drug therapy 
administered in response to an AE. 
 
6.6.3.2.8 
Adverse Event Outcome 
 
• Recovered/resolved: the patient fully recovered from the AE with no residual 
effect observed 
 
• Recovered/resolved with sequelae: the residual effects (e.g., symptoms or 
pathology) of the AE are still present and observable 
 
• Not recovered/not resolved: the AE itself is still present and observable 
• Fatal: the patient dies as a result of the AE 


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• Unknown: outcome of the AE is unknown. 
6.6.3.3 
Pregnancy 
 
Although not considered an AE, it is the responsibility of the Investigator or their 
designee to report any pregnancy in a patient or the patient’s sexual partner that occurs 
during the study. All patients who become pregnant must immediately discontinue the 
study drug and be withdrawn from the study. The patient will be followed to 
completion/termination of the pregnancy. This information is important for both drug 
safety and public health concerns. If a patient is found to be pregnant after the study 
treatment was administered, the Investigator should report this to the CRO and Sponsor 
immediately and document using the Pregnancy Form. 
 
The Investigator must make every effort to follow the patient until completion of 
pregnancy. If the outcome of pregnancy meets the criteria for classification of an SAE, 
the Investigator must follow the procedures for reporting SAEs outlined in Section 6.6.4. 
 
6.6.3.4 
12-lead Electrocardiogram 
 
A standard resting 12-lead ECG will be performed at Screening and at the end of 
induction (Day 7). Additional 12-lead ECGs may be obtained at the Investigator’s 
discretion or if clinically indicated. 
 
6.6.3.5 
Left Ventricular Ejection Fraction 
 
An echocardiography or MUGA scan will be performed during Screening to determine 
the patient’s cardiac ejection fraction for eligibility in the study. 
 
6.6.3.6 
Laboratory Assessments 
 
The time points at which these samples will be collected are shown in the Schedule of 
Study Procedures (Table 6—1) and (Table 6—2). Assessments will be performed and 
evaluated locally. 
 
The following clinical laboratory assessments will be performed: 
 
• Hematology panel: hemoglobin , ANC, and platelet 
• Chemistry (comprehensive metabolic panel): ALT, AST, total bilirubin, 
alkaline phosphatase , BUN, and serum creatinine 
 
• Coagulation panel: anti-factor Xa, PT, aPTT, INR. 
Any clinically significant abnormal laboratory value should be immediately re-checked 
whenever possible, for confirmation before making any decision for the concerned 
patient. It should be documented as an AE/SAE per protocol requirement. 


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A urine pregnancy test will be conducted at Screening for all females of childbearing 
potential to confirm absence of pregnancy. Positive urine test results must be confirmed 
by serum pregnancy test. Results will be analyzed locally. Pregnancy tests may be 
performed at other visits at the discretion of the Investigator. 
 
 
6.6.3.6.1 
Bone Marrow Aspirate/Biopsy 
 
To evaluate disease status, a bone marrow aspirate and biopsy if needed will be done 
within 28 days before starting therapy. Bone marrow aspirate and biopsy will also be 
performed between Days 14-21 to determine the need for re-induction chemotherapy (see 
Section 6.4.1). Subsequent bone marrow examinations are specified in Section 6.5.1. 
Bone marrow aspirate at baseline and follow-up should include analysis by flow 
cytometry and cytogenetic analysis. Bone marrow (or peripheral blood if bone marrow is 
unavailable) should be sent to the institution’s local cytogenetic laboratory for analysis. 
 
For patients with documented CR, confirmatory bone marrow aspirate slides will be 
submitted to the Sponsor or designee. 
 
6.6.3.7 
Vital Signs and ECOG Performance Status 
 
Measurement of vital signs will include an assessment of heart rate, BP, height, and 
weight. Height will be measured once during Screening. Weight will be measured at the 
beginning of each cycle to calculate treatment doses. Vital signs may be repeated for 
clinically significant abnormal findings at the discretion of the Investigator. 
 
Eastern Cooperative Oncology Group performance status will be collected at Screening 
Visit only (see Appendix B). 
 
6.6.3.8 
Physical Examination 
 
All abnormal findings on physical exam will be documented in the source documentation 
and eCRF. New or worsened abnormalities should be recorded as AEs, if applicable. 
 
6.6.4 Reporting Serious Adverse Events 
 
All SAEs will be collected from the time of informed consent until 30 days after the last 
study treatment and regardless of study drug relationship, must be reported by facsimile 
to the CRO within 24 hours of knowledge of the event. The facsimile report should 
include all available information requested on the SAE form (refer to Key Study 
Personnel page for fax number to report SAEs).The SAE form will collect data 
surrounding the event, e.g., the nature of the symptom(s), time of onset in relation to 
initiation of therapy, duration, intensity, and whether or not therapy was interrupted or 
discontinued. The Investigator’s assessment of the probable cause of the event will also 
be included. In addition, relevant medical history, concomitant medications, laboratory 
and diagnostic reports, and procedures, as well as all pertinent medical information 


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related to the event, will also be collected. 
 
The CRO will forward SAE queries directly to the site requesting incomplete or missing 
information. It is the Investigator’s responsibility to be diligent in providing this 
information back to the CRO as soon as it is available. Initial reports of SAEs should not 
be left on telephone voicemails. Always fax SAE reports and follow-up with a telephone 
call if needed. 
 
All sites will follow their institutional requirements for submission of SAEs to their IRB. 
 
6.6.4.1 
Expected Adverse Events 
 
Myelosuppression and its associated complications due to underlying leukemia and/or 
intensive anti-leukemia therapy are expected events during therapy for AML. 
 
Hospitalization or prolongation of hospitalization for the treatment of the following 
events that are known to be associated with myelosuppression from leukemia and/or 
intensive leukemia therapy, are also considered to be expected. These events still need to 
be recorded as AEs on the eCRF: 
 
• Fatigue, weakness and/or shortness of breath associated with anemia 
• Febrile neutropenia 
• Bleeding due to thrombocytopenia e.g., epistaxis, gastrointestinal bleeding 
• Bacteremia, sepsis, or other infections 
• Neutropenic colitis. 
Death due to progression of AML and/or its associated complications are expected in the 
patient population and are listed in Appendix E. Deaths should be reported with 
Investigator’s assessment of causality. 
 
Appendix E also contains a list of known/expected AEs for cytarabine and idarubicin. 
The IB contains expected events known for CX-01 (63). 
 
6.6.4.2 
Investigator’s Notification of the Sponsor 
 
All Investigators will be thoroughly instructed and trained on all relevant aspects of the 
Investigator’s reporting obligations for SAEs. This information, including all relevant 
contact details, is summarized in the Investigator site file. This information will be 
updated as needed. Serious AEs occurring during the study must immediately (within 
24 hours of Investigator’s awareness) be reported per Section 6.6.4 to the recipient 
detailed in the manual. 
 
Serious AEs occurring after the protocol-defined observation period will be processed by 


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the Sponsor according to all applicable regulations. 
 
6.6.4.3 
Notification to the Independent Review Board 
 
Notification to the IRB about all relevant events (e.g., SAEs, SUSARs) will be performed 
by the Sponsor or Sponsor’s designee and/or by the Investigator according to all 
applicable rules/regulations. 
 
6.6.4.4 
Notification to the Authorities 
 
The processing and reporting of all relevant events (e.g., SAEs, SUSARs) to the 
authorities will be done by the Sponsor or Sponsor’s designee and/or by the Investigator 
according to all applicable rules/regulations. 
 
6.6.4.5 
Sponsor’s Notification to the Investigational Site 
 
The Sponsor or designee will inform all investigational sites about reported relevant 
events (e.g., SUSARs) according to all applicable regulations. The Sponsor or Sponsor’s 
designee will send SUSARs to a site once the site initiation visit has occurred and will 
stop sending SUSARs to a site once the last subject End of Treatment Visit for that site 
(30 days after last dose) occurs. 
 
6.6.5 Data and Safety Monitoring Committee 
 
A DSMC will serve as a monitoring advisory group for the study. The primary role for 
the DSMC will be to examine the safety and efficacy throughout the duration of the 
study. 
 
The DSMC will be created to further protect the rights, safety, and well-being of patients 
who will be participating in the study by monitoring their progress and their results. The 
DSMC comprises qualified scientists, who are not Investigators in the study and not 
otherwise directly associated with the Sponsor. The DSMC will be described in detail in 
the DSMC Charter. 
 
The DSMC will monitor data during the study. All activities of the DSMC will be 
documented. This documentation will contain data summaries and analyses provided to the 
committee as well as minutes of any ad-hoc meetings, as necessary. 
 
6.6.6 Pharmacokinetics 
 
Steady-state PK samples will be collected at selected sites only. Pharmacokinetic samples 
will be collected during the induction cycle on Days 3 and 5. 
 
The first 6 patients assigned to a CX-01 dose level (low; 0.125 mg/kg/hour, intermediate; 
0.25 mg/kg/hour, and high doses; 0.325 mg/kg/hour) will have PK’s drawn (consistent 
with the original protocol which included 4 dose groups). 


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The same 6 patients that participate in Day 3 PK sampling will have one additional blood 
sample drawn on Day 5 of treatment. The PK samples may be drawn before the CX-01 
infusion is stopped to change the CX-01 bag and tubing. All PK blood samples must be 
drawn from the opposite arm to the CX-01 IV infusion. 
 
The site will document actual dates and times of sample collection in the source 
documents and eCRF. Any reason for missed or lost samples should be recorded. 
 
Pharmacokinetic blood samples will be processed and may be batch shipped for analysis 
to a bioanalytical laboratory. Full details of sample handling and shipment can be found 
in the Study Operations Manual (also refer to Appendix F for details). 
 
6.7 
Data Quality Assurance 
The Sponsor or Sponsor’s designee performs quality control and assurance checks on all 
clinical studies that it conducts. Before enrolling any patients in this study, the Sponsor or 
Sponsor’s designee and the Investigator will review the protocol, the IB, the eCRFs and 
instructions for their completion, the procedure for obtaining informed consent, and the 
procedure for reporting AEs and SAEs. The Sponsor’s designee will monitor the conduct 
of the study at the site and will verify eCRFs against source documents. Additionally, the 
Sponsor’s designee will use automated validation programs to help identify missing data, 
selected protocol deviations, out-of-range data, and other data inconsistencies. Requests 
for data clarification or correction will be electronically provided to the Investigator for 
resolution. 
 
In accordance with ICH GCP and the Sponsor’s audit plans, this study may be selected 
for audit by representatives from the Sponsor or Sponsor’s designee. Inspection of site 
facilities (e.g., pharmacy drug storage areas, laboratories, etc.) and review of study- 
related records will occur to evaluate the study conduct and compliance with the protocol, 
ICH GCP, and applicable regulatory requirements. 
 
6.8 
Statistical Methods 
 
6.8.1 Determination of Sample Size 
 
A total of 25 evaluable patients per arm will provide 71.8% power for each test 
comparing a dose with control via a Fisher's exact test at 1-sided alpha = 0.15 to detect a 
difference between a control proportion 0.55 and an experimental dose proportion 0.80; 
these tests will be conducted in a fixed sequence: higher dose versus control first and 
lower dose versus control second, with the second test considered exploratory (failed) if 
the first test fails. 
 
6.8.2 Patient Populations Analyzed 
 
The analysis sets that will be used for statistical analyses are as follows: 


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Intent-To-Treat (ITT): All randomized patients. Patients will be analyzed according to the 
treatment to which they are randomized. The ITT Population will be the primary analysis 
set for the efficacy variables. 
 
Per Protocol (PP): Supporting analyses will be conducted on the PP Population, 
comprising all patients randomized and treated without major protocol violations during 
the trial. This population will be documented before final database lock. 
 
Safety: All patients who received at least one dose of study treatment. Patients will be 
included in the analyses according to the treatment they received. The Safety Population 
will be used in the analyses of all safety endpoints. 
 
6.8.3 General Considerations 
 
The following is an overview of the statistical analysis methods to be used in this study. 
Details on the statistical analyses will be given in the Statistical Analysis Plan (SAP). 
Patients will be randomized to one of the following treatment groups in a 1:1:1 ratio: 
 
• Group 1: Idarubicin + Cytarabine, OR 
• Group 2: Idarubicin + Cytarabine plus lower dose CX-01 (0.125 mg/kg/hour), 
OR 
 
• Group 3: Idarubicin + Cytarabine plus higher dose CX-01 (0.25 mg/kg/hour) 
Unless stated otherwise, descriptive summary statistics will include frequency counts and 
percentages for categorical variables and number of observations, mean, standard 
deviation (SD), median, minimum and maximum and the 1st and 3rd quartiles for 
continuous variables. 
 
The final analysis will be done when the last patient completes the study treatment, all 
assessments for disease response, and a Safety Follow-Up Visit approximately 30 days 
after termination of study treatment. All patients will be followed for OS for at least 
18 months. Statistical analysis will be performed using SAS; the version used will be 
specified in the SAP. 
 
6.8.4 Demographics and Other Baseline Characteristics 
 
6.8.4.1 
Patient Disposition 
 
The number and percentage of patients screened, randomized, and treated will be 
presented by treatment group. The reasons for patients discontinued from the treatment 
will be summarized by study stage and treatment group. In addition, the number of 
patients screened and included in each analyses population will be displayed by center. 


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6.8.4.2 
Patient and Disease Characteristics 
 
Descriptive summaries of demographics and baseline characteristics will be presented by 
treatment group and overall for the Safety, ITT, and PP Populations. Comparability of the 
treatment groups with respect to demographic and baseline characteristics will be 
assessed using the descriptive summaries. 
 
The following demographic data will be summarized: 
 
• Age at Screening (years) 
• Race and ethnicity 
• Height (cm) 
• Weight (kg) at baseline. 
The following baseline characteristics will be summarized: 
 
• Stage of AML at diagnosis 
• Time since diagnosis 
• Baseline blasts in bone marrow (%) 
• Baseline peripheral blasts 
• ECOG performance status 
• Baseline LDH 
6.8.5 Medical and Surgical History 
 
Medical and surgical history includes relevant history other than AML. This information 
will be coded using the version of MedDRA currently in effect at the time of database 
lock. 
 
6.8.6 Concomitant Therapy 
 
All non-study medications taken during the study will be coded using the World Health 
Organization Drug Dictionary (WHO-DD) and the Anatomical Therapeutic Chemical 
classification system. Coding will include the drug class and generic drug name. Non- 
study medications taken during the study will be categorized as prior medications, 
concomitant medications, and post treatment medications. Prior medications will be 
defined as non-study medication with a stop date prior to the first dose of study treatment. 
 
Post treatment anti-AML therapies will be coded and summarized. 


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6.8.7 Extent of Study Drug Exposure and Compliance 
 
Extent of study drug exposure will be summarized for the entire study treatment period 
and by cycle. Exposure variables will include duration of study treatment, number of 
dose reductions, number of treatment delays, number of treatment cycles, and dose 
intensity relative to dose levels specified in the protocol. 
 
6.8.8 Efficacy Analysis 
 
6.8.8.1 
Primary Efficacy Outcome Measure 
 
The primary efficacy analysis will be performed on the ITT Population as defined in 
Section 6.8.2. Fisher exact test will be used to compare the proportion of CRs between 
each dose and control. 
 
6.8.8.2 
Secondary Efficacy Outcome Measures 
 
The primary analysis will be repeated using the PP Population as a supportive analysis. 
Complete response rates and confidence intervals will also be reported for key subgroups 
(e.g., randomization strata). Analyses of EFS, LFS, time to neutrophil and platelet 
recovery, and OS will be descriptive. Kaplan-Meier (KM) estimates will be used to 
estimate the survival distribution for each arm and KM plots will be produced to 
accompany these analyses. Confidence Intervals will be reported for medians and KM 
estimates. Duration of response will be analyzed using a similar approach; the analysis 
will account for the competing risk of death and the survival distributions will be 
estimated as cumulative incidence functions. 
 
Mortality rate at Day 30, Day 60, and Day 90 will be reported using descriptive statistics 
in a manner similar to the reporting of the morphologic CR rate. The time to neutrophil 
and platelet recoveries will be reported using the following descriptive statistics: N, 
mean, SD, median, minimum, maximum, and the 1st and 3rd quartiles. 
6.8.9 Subgroup Analysis 
 
Subgroup analyses will be defined in the SAP. All results from these analyses are deemed 
to be exploratory. Exploratory analysis will be descriptive. 
 
6.8.10 Safety Analysis 
 
Safety analysis will be descriptive based on the Safety Population and will involve 
examination of descriptive statistics and individual patient listings for effects of study 
treatment on clinical safety and tolerability. The safety assessment period is from the first 
dose of study treatment until 30 days following the last dose of study treatment. 
 
6.8.10.1 
Adverse Events 
 
All AEs will be categorized by SOC and Preferred Term using the MedDRA dictionary 


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and graded according to NCI-CTCAE v4.03. Treatment-emergent AE summaries will 
include NCI-CTCAE Grade 3 or higher AEs, and AEs resulting in discontinuation of 
study treatment, AEs resulting in death, deaths during the treatment period within 30 days 
of the last study treatment, deaths reported beyond 30 days that are considered study 
drug-related, and the incidence of laboratory values with NCI-CTCAE Grades 3 or 4. 
Particular attention will be upon coagulation parameters and bleeding-related events. 
 
6.8.10.2 
Clinical Laboratory Assessments 
 
Clinical laboratory assessment will be summarized using frequency tables, shift tables, 
and descriptive statistics. Frequency tables and shift tables will be presented by 
NCI-CTCAE grade. Laboratory variables with no NCI-CTCAE group will be presented 
in shift tables with respect to normal range. All laboratory variables will be presented in 
tables of descriptive statistics (mean, SD, etc.) and in graphs. 
 
6.8.10.3 
Vital Signs and ECOG Performance Status 
 
Vital signs variables and ECOG performance status will be summarized using descriptive 
statistics. 
 
6.8.10.4 
Electrocardiogram 
 
Electrocardiogram will be summarized using descriptive statistics. 
 
6.8.11 Pharmacokinetic Analysis 
 
The PK parameters will be summarized by descriptive statistics. A list of PK parameters 
and definitions will be specified in the SAP. 
 
7. 
RISKS AND BENEFITS 
 
The potential risks associated with participation in this study are minimal based on 
available safety data. Such risks are limited to unforeseen adverse interactions between 
idarubicin + cytarabine and CX-01. Heparins, as a class are associated with abnormal 
LFTs, which are generally reversible and of little clinical importance. 
 
Study participants may benefit from participating in the trial if, by mobilizing AML stem 
cells from the protective environment of the bone marrow or through other mechanisms, 
the addition of CX-01 at either of two dose levels results in an enhanced cytotoxic effect 
of idarubicin + cytarabine, although such benefit is not guaranteed. 
 
For further details concerning warnings, precautions, and contradictions, refer to the 
appropriate section of the IB (63). 


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8. 
INVESTIGATORS REGULATORY OBLIGATIONS 
 
8.1 
Pre-study Documentation 
The Investigator must provide the Sponsor or designee with the following documents 
BEFORE consenting any patients: 
 
1. 
All applicable regulatory forms 
 
2. 
Current signed and dated curricula vitae for the Investigator, sub-Investigators, 
and all key personnel listed on the clinical study information form 
 
3. 
Copy of the IRB approval letter for the protocol and informed consent 
 
4. 
Copy of the IRB-approved ICF to be used 
 
5. 
When applicable, a list of the IRB members and their qualifications, and a 
description of the committee’s working procedure 
 
6. 
Copy of the protocol signature page signed by the Investigator 
 
7. 
Fully executed clinical study agreement (CSA) 
 
8. 
Completed FDA Form 1572. 
 
8.2 
Electronic Data Capture 
 
The CRO will supply the investigational site with access to a web based EDC computer 
system. Edit checks and data logic checks are at the point of entry and are validated 
according to company standard operating procedures. All data entered into the system are 
transferred to a secure database maintained by the CRO. 
 
Access to the EDC system at the site, for vendors, at the Sponsor, and at the CRO is 
password protected. Study access is granted to site personnel only after they have been 
trained in the use of the EDC system by web based training at the investigational site. 
 
The EDC system contains a system generated audit trail that captures any changes made 
to a data field, including who made the change, and the date and time it was made. This 
information is available at the Investigator’s site, at the CRO, and at the Sponsor. 
 
Data entries made in the EDC screens should be completed within 5 days of the patient’s 
study visit and must be supported by source documents maintained for all patients 
enrolled in the study. 
 
The data collection tool for this study will be the validated electronic system. Patient data 
necessary for analysis and reporting will entered and transmitted via the electronic 
system. Clinical data management will be performed in accordance with applicable 


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standards and data cleaning procedures. For data coding (e.g., AEs, medication), 
internationally recognized and accepted dictionaries will be used. 
 
At the conclusion of the study all data will be delivered to the Sponsor. 
 
8.3 
Adverse Event Reporting 
 
The Investigator agrees to report all AEs to the Sponsor as described in Section 6.6.3.1. 
Furthermore, the Investigator is responsible for ensuring that any sub-Investigator 
promptly brings AEs to the attention of the Investigator. If applicable, the Investigator is 
also responsible for informing the site’s IRB of all SAEs (per IRB requirements). 
 
8.4 
Review of Source Records 
 
The Investigator agrees that the Study Monitor (and other qualified personnel as 
appropriate) will be allowed to conduct site visits to the investigational facilities for the 
purpose of reviewing source records pertinent to the study. The Investigator will make 
the study files available during monitoring visits. These files will also be available for 
inspection by representatives of the Sponsor, competent authorities and/or the IRB. 
Patients will not be identified by name on any of the study documents utilized by the 
Sponsor for their analysis, and confidentiality of information in medical records will be 
preserved. Every effort will be made to maintain the confidentiality of the patient unless 
disclosure is required by regulations. 
 
8.5 
Monitoring of the Study 
 
The Study Monitor will be responsible for monitoring this clinical trial. The Study 
Monitor will monitor the study conduct, proper eCRF completion, source documentation 
completion and retention, and accurate study drug accountability. The Study Monitor will 
visit the study site at suitable intervals and be in frequent contact through verbal and 
written communication with the site. It is essential that the Study Monitor have access to 
all documents (related to the study and the individual participants) at any time these are 
requested. In turn, the Study Monitor will adhere to all requirements for patient 
confidentiality as outlined in the ICF. The Investigator and Investigator’s staff will be 
expected to cooperate with the Study Monitor, to be available during a portion of the 
monitoring visits to answer questions, and to provide any missing information. 
 
8.6 
Protocol Amendments 
 
Any substantial amendments in the research protocol during the period, for which the 
IRB approval had already been given, will not be initiated without submission of an 
amendment for IRB review and approval. 
 
These requirements for approval will in no way prevent any immediate action from being 
taken by the Investigator in the interest of preserving the safety of all patients included in 
the trial. 


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8.7 
Protocol Deviations 
 
A protocol deviation is any departure from the defined procedures and treatment plans as 
outlined in the protocol version submitted and previously approved by the IRB. Protocol 
deviations have the potential to place participants at risk and can also undermine the 
scientific integrity of the study thus jeopardizing the justification for the research. 
Protocol deviations are unplanned and unintentional events. 
 
Investigational sites will report protocol deviations to their IRB per institutional reporting 
requirements. 
 
8.8 
Change in Investigator 
 
If any Investigator retires, relocates, or otherwise withdraws from conducting the study, 
the responsibility for maintaining records may be transferred to the Sponsor or designee, 
IRB, or another Investigator. The Sponsor or designee must be notified of and agree to 
the change. Regulatory agencies will be notified with the appropriate documentation. 
 
8.9 
Criteria for Termination of the Study or Study Center/Site 
 
8.9.1 Early Termination of the Study 
 
If the Sponsor or its designee, the Investigator or regulatory agency discovers any 
condition arising during the study that indicate that the study or the study site should be 
terminated, this action may be taken after appropriate consultation between the Sponsor 
or its designee and the Investigator. The Sponsor or its designee has the right to terminate 
the participation of either an individual site or the study at any time, for any reason which 
may include the following: 
 
• The incidence and severity of AEs in this or other studies indicates a potential 
health hazard to patients. 
 
• Patient enrollment is unsatisfactory. 
• Data recording is inaccurate or incomplete. 
• Investigator(s) do(es) not adhere to the protocol or applicable regulatory 
guidelines in conducting this study. 
 
• Submission of knowingly false information from the study site to the Sponsor or 
its designee or regulatory authorities. 
 
In the event that the study is terminated early, the Sponsor or its designee will provide 
specific guidance to investigational sites regarding the end of study procedures. 


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8.10 
Clinical Study Report 
 
A clinical study report (CSR) will be prepared following the completion of the study. 
 
8.11 
Confidentiality 
All unpublished information that the Sponsor gives to the Investigator shall be kept 
confidential and shall not be published or disclosed to a third party without the prior 
written consent of the Sponsor. 
 
When the Sponsor generates reports for presentations to regulatory agencies, one or more 
of the Investigators who has/have contributed significantly to the study may be asked to 
endorse the final report. 
 
The Investigator shall not make a patent application based on the results of this study and 
shall not assist any third party in making such an application without the written 
authorization of the Sponsor unless otherwise specified in the CSA. 
 
8.12 
Records Retention 
 
Essential documents must be retained for longer than 5 years after completion of the 
study, 2 years after the final marketing authorization in an ICH region or until at least 
2 years have elapsed since the discontinuation of clinical development of the study drug. 
If it becomes necessary for the Sponsor or the Competent Authority to review any 
documentation relating to the study, the Investigator must permit access to such records. 
 
Study files may be discarded upon written notification by the Sponsor. To avoid error, the 
Investigator must contact the Sponsor before destroying any records or reports pertaining 
to the study, to ensure that retention is no longer required. Other source documents, such 
as patient’s medical records, must be retained for the maximum period of time permitted 
by the hospital or institution and until such time when the Investigator is informed by the 
Sponsor that there is no further need to do so. 
 
In addition, in accordance with the Investigator agreement, the Sponsor should be 
contacted if the site’s Principal Investigator plans to leave the investigational site so that 
appropriate arrangements can be made. 


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10. 
APPENDICES 
 
APPENDIX A – Acute Myeloid Leukemia Response Criteria 
 
The IWG consensus criteria for treatment response in AML will be used to evaluate 
response to treatment. 
 
Definitions of Remission 
 
Morphologic complete remission (CR): ANC >1000/μL, platelet count >100,000/μL, 
<5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. 
 
Morphologic CR with incomplete blood count recovery (CRi): CRi, which is CR 
without recovery of neutrophils and/or platelets (ANC may be <1000 μL and/or platelet 
count <100,000/μL). 
 
Partial remission (PR): ANC >1000/μL, platelet count >100,000/μL and at least a 50% 
decrease in the percentage of marrow aspirate blasts to 5 to 25%, or marrow blasts <5% 
with persistent Auer rods. 
 
Progressive Disease 
 
Progressive disease (PD) is defined as any one of the following: 
 
• More than 50% increase in bone marrow blast % from best assessment (with a 
minimum threshold of 20% blasts in the marrow). 
 
• >50% increase in circulating malignant blasts (with absolute blasts >1000/μL). 
• Development of biopsy-proven extramedullary leukemia (if the patient has 
extramedullary disease at baseline then PD will be defined by blood and marrow 
criteria or if new sites of extramedullary disease appear). 
 
In patients who present with initial marrow blast percentage sufficiently high to preclude 
the ability to base disease progression on a >50% increase in marrow blast percentage; 
disease progression should be based on peripheral blood criteria or development of 
extramedullary leukemia. 
 
Stable Disease 
 
Patients who fail to achieve CR, CRi or PR and who do not have criteria for PD will be 
defined as having stable disease. If the patient dies prior to response assessment at the 
end of Cycle 1, then they will be classified as “Indeterminate”. 
 
Relapse from CR or CRi 


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Page 77 of 89 
CONFIDENTIAL 
 
 
Reappearance of leukemia blasts in the peripheral blood; or >5% blasts in the bone 
marrow not attributable to another cause (e.g., recovery of normal cells following 
chemotherapy-induced aphasia); or appearance or reappearance of extramedullary disease 
and the bone marrow blast percentage is >5% but < or equal to 20%, than a repeat bone 
marrow performed at least 7 days after the first marrow examination and documenting 
bone marrow blast percentage is >5% is necessary to establish relapse. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 78 of 89 
CONFIDENTIAL 
 
 
APPENDIX B – ECOG Performance Score 
 
Grade 
Description 
0 
Fully active, able to carry on all predisease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. 
Up and about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
5 
Dead 
Source: As published in Am. J. Clin. Oncol. (CCT) 1982; 5:649-655. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 79 of 89 
CONFIDENTIAL 
 
 
APPENDIX C – Estimated Creatinine Clearance – Cockcroft Gault Formula 
 
(As published in Nephron 1976; 16:31-41) 
 
Clcr = (140 – age) x BM x GF 
 
Scr x 72 
 
 
BM = body mass (kg) 
 
GF = gender correction factor (0.85 in females; 1.00 in males) 
Scr = serum creatinine (mg/dL) 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 80 of 89 
CONFIDENTIAL 
 
 
APPENDIX D – Child-Turcotte-Pugh Classification of Severity of Cirrhosis 
 
Parameter 
Points Assigned 
1 
2 
3 
Ascites 
Absent 
Slight 
Moderate 
Bilirubin 
<2 g/dL 
(<34.2 
micromol/liter) 
2 to 3 mg/dL 
(34.2 to 51.3 
micromol/liter) 
>3 mg/dL 
(>51.3 micromol/liter) 
Albumin 
>3.5 g/dL 
(35 g/liter) 
2.8 to 3.5 g/dL 
(28 to 35 g/liter) 
<2.8 g/dL 
(<28 g/liter) 
Prothrombin time 
Seconds over 
control 
<4 
4 to 6 
>6 
INR 
<1.7 
1.7 to 2.3 
>2.3 
Encephalopathy 
None 
Grade 1 to 2 
Grade 3 to 4 
Source: website: www.uptodate.com, accessed 12 March 2015. 
Modified Child-Turcotte-Pugh classification of the severity of liver disease according to the degree of ascites, 
the serum concentrations of bilirubin and albumin, the prothrombin time, and the degree of encephalopathy. 
A total Child-Turcotte-Pugh score of 5 to 6 is considered class A (well-compensated disease); 7 to 9 is class 
B (significant functional compromise); and 10 to 15 is class C (decompensated disease). These classes 
correlate with one- and two-year patient survival: class A: 100 and 85%; class B: 80 and 60%, and class C: 
45 and 35%. 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 81 of 89 
CONFIDENTIAL 
 
 
APPENDIX E – Expected Adverse Events for Cytarabine and/or Idarubicin 
 
For this protocol only, certain AEs/Toxicity Grades are exceptions to the Expedited 
Reporting Guidelines because the AEs are considered as “Expected” with the 
administration of cytarabine and idarubicin. The following AEs must be reported 
through the routine AE or SAE reporting mechanism, as appropriate: 
 
CTCAE 
Category 
Adverse Event 
Grade 
Chemotherapy 
Attribution 
Blood & 
Lymphatic 
Bone marrow 
suppression/failure 
1-4 
 cytarabine 
 idarubicin 
Neutropenia 
Febrile neutropenia 
1-4 
3-4 
 cytarabine 
 idarubicin 
Thrombocytopenia 
1-4 
 cytarabine 
 idarubicin 
Pancytopenia 
1-4 
 cytarabine 
 idarubicin 
Reticulocyte count, decreased 
1-4 
 cytarabine 
 idarubicin 
Hemorrhage/bleeding 
(secondary to 
thrombocytopenia) 
1-4 
 cytarabine 
 idarubicin 
Anemia 
Anemia (megaloblastic) 
1-4 
1-2 
 cytarabine 
 idarubicin 
General 
Disorders 
Fatigue 
1-3 
 cytarabine 
 idarubicin 
Fever 
1-4 
 cytarabine 
 idarubicin 
Chills 
1-3 
 cytarabine 
 idarubicin 
Injection site reaction/cellulitis, 
pain, stinging or burning 
sensation, inflammation 
1-4 
 cytarabine 
 idarubicin 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 82 of 89 
CONFIDENTIAL 
 
 
 
CTCAE 
Category 
Adverse Event 
Grade 
Chemotherapy 
Attribution 
Tissue necrosis (if 
extravasation) 
3-4 
 cytarabine 
 idarubicin 
Infections 
1-4 
 cytarabine 
 idarubicin 
Edema/swelling 
1-3 
 cytarabine 
 idarubicin 
Respiratory, 
Thoracic and 
Mediastinal 
Disorders 
Pulmonary toxicity 
1-4 
 cytarabine 
 idarubicin 
Dyspnea 
1-4 
 cytarabine 
 idarubicin 
Adult respiratory distress 
syndrome (ARDS) 
3-4 
 cytarabine 
 idarubicin 
Pulmonary edema 
1-4 
 cytarabine 
 idarubicin 
Oropharyngeal pain 
1-4 
 cytarabine 
 idarubicin 
Pulmonary allergy 
1-4 
 idarubicin 
Interstitial pneumonitis 
2-4 
 cytarabine 
 idarubicin 
Gastrointestinal 
Disorders 
Diarrhea 
1-4 
 cytarabine 
 idarubicin 
Bowel necrosis 
3-4 
 cytarabine 
Necrotizing colitis 
3-4 
 cytarabine 
Abdominal or stomach 
pain/tenderness/cramping 
1-3 
 cytarabine 
 idarubicin 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 83 of 89 
CONFIDENTIAL 
 
 
 
CTCAE 
Category 
Adverse Event 
Grade 
Chemotherapy 
Attribution 
(peritonitis) 
Typhlitis (neutropenic 
enterocolitis) 
3-4 
 cytarabine 
 idarubicin 
Pneumatosis intestinalis 
1-4 
 cytarabine 
Nausea 
1-3 
 cytarabine 
 idarubicin 
Vomiting 
1-4 
 cytarabine 
 idarubicin 
Ulceration/Inflammation: 
Oral ulcer/stomatitis/mouth, 
throat 
Esophageal ulcer/esophagitis 
Anal ulcer/inflammation 
Other GI ulceration 
1-4 
 cytarabine 
 idarubicin 
Pancreatitis 
1-4 
 cytarabine 
 idarubicin 
Hyperuricemia 
1-4 
 cytarabine 
 idarubicin 
Mucositis 
1-4 
 cytarabine 
 idarubicin 
Vascular 
Hypotension 
1-2 
 cytarabine 
 idarubicin 
Eye Disorders 
Corneal toxicity (ocular pain, 
tearing, foreign-body 
sensation, photophobia, blurred 
vision) 
2-4 
 cytarabine 
 idarubicin 
Hemorrhagic conjunctivitis 
1-4 
 cytarabine 
 idarubicin 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 84 of 89 
CONFIDENTIAL 
 
 
 
CTCAE 
Category 
Adverse Event 
Grade 
Chemotherapy 
Attribution 
Hepatobiliary 
Hepatic failure 
3-4 
 cytarabine 
Hepatic function, abnormal 
3-4 
 cytarabine 
 idarubicin 
Liver abscess/ injury 
3-4 
 cytarabine 
Jaundice (hyperbilirubinemia) 
3-4 
 cytarabine 
 idarubicin 
Aplasia 
1-4 
 idarubicin 
Cardiovascular 
Cardiomyopathy 
1-4 
 cytarabine 
 idarubicin 
Cardiomegaly 
1-4 
 cytarabine 
 idarubicin 
Congestive heart failure (CHF) 
 idarubicin 
Left ventricular ejection 
fraction (LVEF), decreased 
2-4 
Use 
%drop 
from 
baseline 
 idarubicin 
Arrhythmias (atrial 
fibrillation/others) 
1-4 
 idarubicin 
Abnormal ECG 
1-4 
 cytarabine 
 idarubicin 
Cardiac arrest 
4 
 cytarabine 
 idarubicin 
Chest pain 
1-3 
 cytarabine 
 idarubicin 
Myocardial infarction 
2-4 
 cytarabine 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 85 of 89 
CONFIDENTIAL 
 
 
 
CTCAE 
Category 
Adverse Event 
Grade 
Chemotherapy 
Attribution 
 idarubicin 
Infections and 
Infestations 
Infection (secondary to 
neutropenia/granulocytopenia) 
2-4 
 cytarabine 
 idarubicin 
Sepsis 
4 
 cytarabine 
 idarubicin 
Pneumonia 
2-4 
 cytarabine 
 idarubicin 
Immune System 
Disorders 
Anaphylaxis/Allergic edema 
1-4 
 cytarabine 
 idarubicin 
Metabolism 
Anorexia (decreased appetite) 
2-4 
 cytarabine 
 idarubicin 
Investigations/ 
Laboratory 
Abnormalities 
ALT 
1-4 
 cytarabine 
 idarubicin 
AST 
1-4 
 cytarabine 
 idarubicin 
Alkaline Phosphatase 
1-4 
 cytarabine 
 idarubicin 
GGT 
1-4 
 cytarabine 
 idarubicin 
Bilirubin, increased 
1-4 
 cytarabine 
 idarubicin 
Creatinine, increased 
2-4 
 idarubicin 
Uric acid, increased 
1-4 
 cytarabine 
 idarubicin 
Proteinuria 
1-3 
 cytarabine 
 idarubicin 
Electrolyte abnormalities 
1-4 
 cytarabine 
 idarubicin 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 86 of 89 
CONFIDENTIAL 
 
 
 
CTCAE 
Category 
Adverse Event 
Grade 
Chemotherapy 
Attribution 
Platelet count, decreased 
1-4 
 cytarabine 
 idarubicin 
WBC, decreased 
1-4 
 cytarabine 
 idarubicin 
Musculoskeletal, 
Connective 
Tissue and Bone 
Disorders 
Myalgias & Arthralgias 
(muscle pain/joint pain) 
1-3 
 cytarabine 
 idarubicin 
Cytarabine Syndrome: 
Fever, myalgia, bone pain, 
chest pain, rash, conjuncitvities 
and malaise 6-12 hours 
following drug administration. 
1-3 
 cytarabine 
Nervous System 
Disorders a 
Paresthesia 
1-3 
 cytarabine 
 idarubicin 
Sensory peripheral neuropathy 
and/or motor peripheral 
neuropathy 
1-4 
 cytarabine 
 idarubicin 
Neuralgia/neuritis 
1-3 
 cytarabine 
 idarubicin 
Dizziness 
1-3 
 cytarabine 
 idarubicin 
Depressed Level of 
Consciousness (Mental Status 
Changes) 
 idarubicin 
Seizures 
1-4 
 cytarabine 
 idarubicin 
Headache 
1-3 
 cytarabine 
 idarubicin 
Syncope/fainting 
3 
 cytarabine 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 87 of 89 
CONFIDENTIAL 
 
 
 
CTCAE 
Category 
Adverse Event 
Grade 
Chemotherapy 
Attribution 
 idarubicin 
Cerebellar and cerebral 
dysfunction, including the 
following AE/SAEs: 
• 
Personality changes 
• 
Somnolence 
• 
Convulsion 
• 
Coma 
• 
Stroke-like episodes 
1-4 
 cytarabine 
 idarubicin 
Renal & 
Urinary 
Acute kidney injury 
1-4 
 cytarabine 
Renal impairment, disorder 
1-4 
 cytarabine 
 idarubicin 
Urinary retention 
1-4 
 cytarabine 
 idarubicin 
Hemolytic uremic syndrome 
1 or 3 
 cytarabine 
 idarubicin 
Hyperuricemia 
1,3-4 
 cytarabine 
 idarubicin 
Skin 
Alopecia 
1-2 
 cytarabine 
 idarubicin 
Rash 
1-3 
 cytarabine 
 idarubicin 
Hand-foot syndrome/Palmar 
plantar erythrodysaesthesia 
(PPE) (redness, swelling, pain 
on palms of hands/soles of feet 
1-3 
 cytarabine 
 idarubicin 
Ulceration, skin 
1-4 
 cytarabine 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 88 of 89 
CONFIDENTIAL 
 
 
 
CTCAE 
Category 
Adverse Event 
Grade 
Chemotherapy 
Attribution 
Desquamation, peeling, scaly, 
exfoliation of skin 
1-4 
 cytarabine 
Urticaria/Hives, skin 
1-3 
 cytarabine 
 idarubicin 
Pruritis, skin 
1-3 
 cytarabine 
Freckling, skin 
1-3 
 cytarabine 
Reproductive 
and Fertility 
Teratogenicity, Embryotoxicity 
4 
 cytarabine 
 idarubicin 
Sperm abnormalities 
4 
 cytarabine 
Congenital 
Distal limb defects (upper and 
lower extremities) 
Ear deformities 
4 
 cytarabine 
 idarubicin 


Cantex Pharmaceuticals, Inc. 
CX-01 
Clinical Study Protocol 
Protocol No.: 
CNTX-CX-01-2015-AML-1 
Protocol Version 3.0 
Incorporating Amendment 2 
JAN 13, 2017 
Page 89 of 89 
CONFIDENTIAL 
 
 
APPENDIX F – Blood Sample Handling 
 
Blood sample collection procedure, and sample process, storage and shipment 
 
• The study site will be provided with 4.5 mL tubes with 3.2% trisodium citrate 
• Draw and fill the 4.5 mL tube containing 3.2% trisodium citrate (completely fill 
with blood to minimize citrate dilution) 
 
• Within 30 minutes of collection, centrifuge tube for 15 minutes at 3000 g at 16°C/ 
60.8ºF. Blood samples must be kept on ice until they are centrifuged (a delay 
in centrifuging and separating plasma should not exceed one hour because 
the platelet factor leaches out of platelets and binds CX-01 resulting in 
erroneous CX-01 values) 
 
• Using a plastic pipette, transfer 2 mL of plasma from the tube into two provided 
cryogenic vials; 1 mL in each tube. Each of the two 1 mL-cryogenic vials must be 
labeled: 
 
"CX-01 concentration" and will also include: The sample #, patient's 
randomization/Study ID #, Initials, Study site #, Protocol # (CNTX-CX- 
01-2015-AML-2) and collection date/time. 
 
• Labeled 1 mL/cryogenic tubes must be stored immediately in a -60°C to 80°C 
freezer 
 
Once the full set of blood samples from a patient is complete, all the resulting vials must 
be shipped under cryogenic conditions (dry ice) to the bioanalytical laboratory (see Study 
Operations Manual for name of lab and notification number). 
 
Please call the bioanalytical laboratory to notify them prior to shipments. Please ship 
specimens via FedEx only on Monday, Tuesday or Wednesday to prevent thawing and 
sample loss. 

SAP_001.pdf: 
Statistical Analysis Plan 
 
Protocol Title: A Randomized, Phase II Study of CX-01 Combined With Standard Induction 
Therapy for Newly Diagnosed Acute Myeloid Leukemia 
 
Protocol Number: CNTX-CX-01-2015-AML-1 (NCT02873338) 
 
Date: 20 March 2018 
  
 


COVA- 


 
 
Cantex Pharmaceuticals, Inc. 
 
Protocol No.: CNTX-CX-01-2015-AML-l 
A Randomized, Phase II Study of CX-01 Combined With Standard Induction Therapy for Newly 
Diagnosed Acute Mycloid Leukemia 
 
Covance Study ID: 000000146201 
STATISTICAL ANALYSIS PLAN 
Version:  Final 
Date of Issue: 20 March 2018 
 
 
 
Cantcx Pharmaceuticals, Inc. 
Cantex Pharmaceuticals, Inc. 
1792 Bell Tower Lane 
Weston, Florida 33326 
Author: Steve Su 
 
Covance Clinical Development Services 
Covance Inc. 
210 Carnegie Center 
Princeton, New Jersey 08540-6233 
USA 
Suite 3.02, Level 3 
Building  A, 97  Waterloo Road 
Macquarie Corporate Centre 
Macquarie Park 
New South Wales 2113, Australia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVANCE INC. CONl''/DENTIAL  
Page I  of 34 
ST-AD-008 version 03 


Statistical  Analysis l'hm 
Version: Final  
-,- 
  
l)ate,of Issue: 20_Mars]d018_    
Caniex Pharmaceuticals, Inc, Protocol No, CNTX-CX-01 2015 AML J Covance Study ID: 000000146201 
 
 
 
APPROVALS 
The undersigned agree that all required reviews of this document are complete, and approve 
this Statistical Analysis Plan as finaL Programming oftbe tables, figures imd listings based 
upon the specifications within this document can proceed. 
Covance Approval: 
,--<_·'_c, /  /·:'· 
//'<. _•', 
/ /·,// [.,./ / i 
i 
/ ( • 
 ---+'   -·-;,,, {"   I         l..t.· 
i +"'--i--'--"l,,"',""'------------ 
Signarnre / 
 
 _Toyoko Oguri. Senior Manager,/ Biostatistics and Statistical Programming 
Printed Name/Title 
 
 
 
  
 ,.J) ··· /!1tv ··  ;Jv /{     
Daw 
 
 Suzanne Balandis, PharmD / Vice President, Clinical Operations 
 
Printed NmneiTitle 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVANCE INC. CONFIDENT/AL 
Page 2 of 34 
STwAD 008 version fl2 


Statistical  Analysis Plan 
Version: Final 
Date of  Issue: 20 March 2018 
 
 
Cantcx  Pharmaceuticals. Inc.  Protocol  No. CNTX-CX-0 I  2015 AML  I     Covance Study  ID: 00000014620 I 
 
 
REVIEWERS 
The following reviews of the SAP were conducted: 
 
Name and Title 
Role 
Version Last 
Reviewed 
Company/ 
Ore:anization 
 Richard McNally 
Peer Review Statistician 
Draft 01 
Covance 
 Rachana Agarwal 
Lead Programmer 
Draft 01 
Covance 
 Toyoko Oguri 
Senior Manager 
(Statistics) 
Draft 04 
Covance 
 Virginia Rhodes 
Senior Medical Director 
Draft 02 
Covance 
 Stephen Marcus. 
M.D./Chief Executive 
Officer 
Project Physician 
Draft 02 
Cantex 
 
VERSION HISTORY 
 
Version Number 
-···~.. -,.. 
Version Date 
Summary and rational of chane:c(s) 
···-···~""'' 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVANCE INC. CONFIDEN71AL 
Page  3 of34 
ST-i\D-008 version 02 


Statistical  Analysis Plan 
Version: Final 
Date of lssne: 20 March 2018 
Cantex  Pharmaceuticals. Inc.  Protocol  No. CNTX-CX-01  2015  AMI.  I    Covance Study  ID: 000000146201 
 
 
TABLE OF CONTENTS 
APPROVALS ................................................................................................................... 2 
REVIEWERS ................................................................................................................... 3 
VERSION HISTORY ...................................................................................................... 3 
GLOSSARY OF ABBREVIATIONS ............................................................................. 6 
STATISTICAL  ANALYSIS PLAN AMENDMENT 1 ................................................. 7 
I 
SOURCE DOCUMENTS ................................................................................................. 8 
2 PROTOCOL DETAILS ............................................................................................. 8 
2.1 Study Objcctives ................................................................................................ 8 
2.2 
Primary Objectives ............................................................................................ 8 
2.3 Secondary Ob.iectives ............................................................................................. 8 
2.4 
Exploratory Objectives ...................................................................................... 9 
2.5 Overall Study Design ......................................................................................... 9 
2.6 Sample Size and Power .................................................................................... 12 
3 EFFICACY  AND SAFETY VARIABLES ................................................................... 12 
3.1 
Primary Efficacy Endpoint(s) .......................................................................... 12 
3.2 
Secondary Efficacy Endpoints ......................................................................... 13 
3.3 
Safety Endpoints ............................................................................................... 14 
4 PHARMACOKINETIC/PHARMACODYNAMIC VARIABLES ......................... 14 
5 ANALYSIS POPULATIONS........................................................................................ 14 
6 DATA HANDLING.................................................................................................. 15 
6.1 
Time points and Visit Windows ....................................................................... 15 
6.2 
Handling of Dropouts or  Missing Data (where applicable) ............................ 15 
7 STATISTICALMl THODS ................................................................................ 16 
7.1 
General Principles ............................................................................................ 16 
7.2 Subject Disposition and Data Sets Analyzed ................................................... 17 
7.3 
Protocol Deviations .......................................................................................... 17 
7.4 
Demographics  and Other Baseline Characteristics ......................................... 18 
7.4.1 
Medical History.............................................................................................. 18 
7.4.2 
Prior, Post treatment (anti AML) and Concomitant Medications .................. 19 
7.5 
Measurements of Treatment Exposure and Study Drug Usage Rate ............... 19 
7.6 
Efficacy .................................................................................................................. 22 
7.6.1 
Primary Efficacy Analysis ........................................................................ 22 
COVANCE INC. CONFIDENTIAL 
Page  4 of34 
ST-J\D-008  version 02 


Statistical  Analysis Plan 
Version: Final 
Date of Issue: 20 March 2018 
Cantex  Pharmaceuticals, Inc.  Protocol  No.  CNTX-CX-01  2015  AML  I     Covance Study  ID: 000000146201 
 
 
7.6.2 Secondary Enicacy Analysis ..................................................................... 22 
7.6.3 Sensitivity Analysis ................................................................................... 23 
7.6.4 Subgroup Analysis ..................................................................................... 23 
7.6.5 
Exploratory Analysis ..................................................................................... 23 
7.7 Safety ..................................................................................................................... 23 
7.7.1 Adverse Events .......................................................................................... 23 
7.7.2 Laboratory Evalualions .............................................................................. 25 
7.7.3 Vital Signs and ECOG performance status ............................................... 25 
7.7.4 Electrocardiograms .................................................................................... 25 
7.8 
Interim Analysis ................................................................................................... 26 
8 
CHANGES  FROM  PLANNED  ANALYSES IN PROTOCOL .................................. 26 
9 DATA ISSUES .............................................................................................................. 26 
IO REl<ERENCES .................................................................................................................. 26 
11  APPENDICES..................................................................................................................... 28 
APPENDIX I - SCHEDULE OF EVENTS ....................................................................... 28 
APPENDIX II - TABLE, FIGURE AND LISTING SHELLS ....................................... 34 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVANCE INC. CONFfl)ENT!AL 
Page 5 of 34 
ST-/\D-008 VCl'sion 02 


Statistical  Analysis Plan 
Version: Final 
Date of  Issue: 20  March 2018 
Cantex  Pharmaceuticals, Inc.  Protocol  No. CNTX-CX-0 I  2015 AML  I    Covance Study  ID: 00000014620 I 
 
 
GLOSSARY OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
ALT 
AML 
ANC 
AST 
ATC 
AUC 
BP 
BUN 
CBC 
Cl 
CR 
CRi 
CRp 
DSMC 
ECG 
ECOG 
EFS 
FU 
INR 
ITT 
IWG 
KM 
LDH 
LFS 
MUGA 
 
NCI-CTCAE 
NSW 
OS 
PK 
pp 
PT 
SAE 
SAP 
SD 
soc 
TBD 
TEAE 
USA 
Adverse Event 
Alanine Aminotransferase 
Acute Myeloid Leukemia 
Absolute Neutrophil Count 
Asparlale Aminotransferase 
Anatomical Therapeutic Chemical 
Area Under Curve 
Blood Pressure 
Blood  Urea Nitrogen 
Complete Blood Count 
Confidence Interval 
Complete Remission 
Complete Remission without recovery of neulrophils and/or platelets 
Complete Remission without recovery of platelets 
Data Safety Monitoring Commillee 
Electrocardiogram 
Eastern Cooperative Oncology Group 
Event-Free Survival 
Follow-Up 
International Normalized Ratio 
Intent-To-Treat 
International Working Group 
Kaplan-Meier 
Lactate Dehydrogenase 
Leukemia-Free Stale/Survival 
Multi Gated Acquisition 
National Cancer Institute-Common Terminology Criteria For Adverse 
Events 
New South Wales 
Overall Survival 
Phannacokinetic 
Per Protocol 
Prolhrornbin Time 
Serious Adverse Event 
Statistical Analysis Plan 
Standard Deviation 
System Organ Class 
To Be Determined 
Treatment Emergent Adverse Event 
United States Of America 
 
CO/>ANCE INC. CONFIDENTIAL 
Page  6 of34 
ST-i\D-008  version 02 


Statistical  Analysis Plan 
Version: Final 
Date of Issue: 20 March  2018 
Cantex  Pharmaceuticals. Inc.  Protocol  No. CNTX-CX-0 I  2015  AML  I     Covance Study  ID: 00000014620 I 
 
 
STATISTICAL ANALYSIS PLAN AMENDMENT I 
Nol applicable 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVANCE INC CONFIDENTIAL 
Page  7 of 34 
ST-t\D-008  version 02 


Statistical  Analysis Plan 
Version: Final 
Date of  Issue: 20  March 2018 
Cantex  Pharmaceuticals,  Inc.  Protocol  No. CNTX-CX-01  2015  AML  I     Covance Study  ID: 000000146201 
 
 
l 
SOURCE DOCUMENTS 
The Statistical Analysis Plan (SAP) was wriUen based on the following documentation: 
 
Document 
Date 
Version 
Protocol 
04 February 2016 
1.0 
Protocol Amendment 1 
16 September 2016 2.0 
Protocol Amendment 2 
13 January 2017 
3.0 
eCRF 
25 July 2016 
1.0 
eCRF Amendment 
16 August 2017 
1.0.4 
 
2 
PROTOCOL DETAILS 
2.1 Study Objectives 
 
This randomized, phase II study  ofCX-01  is designed  to assess  the effect of adding CX-01 
at one of the two different dose levels to standard induction and consolidation therapy for 
newly diagnosed patients with AML. 
 
2.2 
Primary Objectives 
 
The primary objectives are: 
 
• 
To assess whether 2-0, 3-0 desulfatcd heparin (CX-0 I), administered at any or all 
studied dose levels in conjunction with standard induction  therapy  for AML 
increases the morphologic complete remission (CR) rate based on International 
Working Group (IWG) criteria. 
 
• 
To assess the safety and tolerability of CX-01, administered  at  two  studied  dose 
levels in conjunction with standard induction therapy for AML. 
 
2.3 
Secondary Objectives 
 
The secondary efficacy objectives are: 
 
To assess whether CX-01, administered at any or all studied dose levels in conjunction with 
standard induction and consolidation therapy fr)r AML improves: 
 
• 
Event-free survival (EFS) 
 
• 
Leukemia-free survival (LFS) 
 
• 
Overall survival (OS) 
 
 
 
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• 
Co111positc CR rate: incidence of CR+ CRi+CRp 
 
• 
Duration of morphologic CR 
 
• 
30-day mortality  (in the induction  cycle) 
 
• 
60-day  mortality  (in the induction cycle) 
 
• 
90-day  mortality  (in the induction cycle) 
 
• 
Days until neutropbil recovery to? 1,000/ µL 
 
• 
Days until platelet recovery to? I 00,()00/ µL 
 
2.4 
Exploratory Objectives 
 
The following items are not specified in the protocol but arc still of clinical importance and 
will be analyzed: 
 
• 
Duration of composite CR (if present) 
 
• 
Days until neutrophil  recovery  to ?  500/ µL 
 
• 
Days until  platelet  recovery  to?   20,000/ tL 
 
 
2.5 
Overall Study Design 
 
This is an exploratory phase II, open-label, rando111ized, 111ulticcntcr, parallel group trial to 
dctcr111inc whether there is evidence that the addition of either or both different dose levels of 
CX-01 to standard induction therapy (idarubicin + cytarabine) and consolidation therapy has an 
additive therapeutic effect in newly diagnosed AML patients when co111parcd  to patients 
receiving standard induction che111otherapy alone. 
 
To be eligible to participate in the study, patients 111ust meet the following criteria: 
 
I. 
Newly diagnosed, de novo or secondary, previously untreated AML 
2. 
Age 60 or above 
3. 
Eastern Cooperative Oncology Group (ECOG) performance status of Oto 2 
4. 
Cardiac ejection fraction 45% (asdetermined by echocardiography or multi gated 
acquisition scan) 
5. 
Adequate hepatic and renal function determined by the following laboratory values: 
• 
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 x upper limit 
of normal (ULN) 
 
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Cantcx   Pharmaceuticals,  Inc.  Protocol   No.  CNTX-CX-01   2015  AML   I      Covance  Study  ID: 000000146201 
 
 
• 
Bilirubin <2.5 x ULN 
• 
Calculated crcatininc clearance by Cockcrofl Gault forrnula >30 rnL/rnin. 
6. 
Able to provide informed consent and have signed an approved consent forrn that 
conforms to federal and institutional guidelines. 
 
Patients who meet any of the following criteria will not be eligible to participate in the study: 
 
I. 
Patients with acute promyclocytic lcukernia based  on the presence oft(15; I 7)(q22;q 12) 
as determined by karyotyping, fluorescence in situ hybridization or polymerase chain 
reaction 
2. 
Prior chemotherapy for AML (including invcstigational therapy); prior hydroxyurca to 
control white blood cell count and a single intrathecal administration of cytarabinc for 
CNS prophylaxis is allowed 
3. 
Prior intensive chemotherapy or stem cell transplantation for treatment of 
myelodysplastic syndrome (prior treatment with hyporncthylating agents and 
lenalidomidc arc allowed) 
4. 
Presence of central nervous systcrn leukcrnia 
5. 
Presence of significant active infection that is not controlled in the opinion of the 
Investigator 
6. 
Presence of significant active bleeding 
7. 
History of severe congestive heart failure or other cardiac disease that contraindicates the 
use of anthracyclines, including idarubicin 
8. 
Pre-existing liver disease (such as CHILD-Pugh Class B or C liver disease) 
9. 
Renal insufliciency which rnight adversely affect schedule and dose of therapy with 
cytarabine as well as rnanagcment of tumor lysis syndrome 
I 0. 
History of drug addiction within the last 6 months 
I I. 
Known history of positive Hepatitis 13 surface antigens 
12. 
Known history of positive test for Human lmrnunodeficicncy Virus antibodies 
13. 
Psychiatric or neurologic conditions that could compromise patient safety or compliance, 
or interfere with the ability to give proper informed consent 
14. 
History of other active malignant disease within the past 3 years, other than cured basal 
cell carcinoma of the skin, cured in situ carcinoma of the cervix, or localized prostate 
cancer that has received definitive therapy. Such prostate cancer patients who are 
receiving hormonal therapy are eligible 
15. 
Patients receiving any form of anticoagulant therapy (heparin flushes for IV catheter 
permitted) 
16. 
Presence of a known bleeding disorder or coagulation abnorrnality (including but not 
limited to a PTT >40 seconds) or any condition that requires maintenance of platelet 
counts at 50,000/"tL or higher 
17. 
Pregnant or breast feeding patients 
18. 
Patients of childbearing potential not using adequate contraception. 
 
Approximately 75 patients will be randomized in a I: I: I ratio to one of the following study 
treatment groups: 
 
 
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Cantex Pharmaceuticals, Inc. Protocol No. CNTX-CX-0 I 2015 AML I Covance Study ID: 00000014620 I 
 
 
• Group I: ldarubicin + Cytarabine, OR 
• Group 2: ldarubicin + Cylarabine plus lower dose CX-01 (0.125 mg/kg/hour), OR 
• Group 3: ldarubicin + Cytarabine plus higher dose CX-0 I (0.25 mg/kg/hour) 
 
Eligible patients who meet the inclusion criteria and do not meet any of the exclusion criteria 
and have provided informed consent will be enrolled in the study. Each patient will participate 
in the study for approximately 18 months from the time of informed consent through final 
study contact, or until they withdraw from the study or the study is terminated by the Sponsor. 
 
Overall survival data will be collected every 3 months until death or until the end of study by 
the investigational sites. The end of study will occur approximately 18 months afler the last 
patient is randomized. Overall survival data will be collected every 3 months until death or 
until the end of study  by  the investigational sites. The end of study will  occur 
approximately 18 months afler the last patient is randomized. 
 
A Data and Safety Monitoring Commiltec (DSMC) will meet periodically to review the 
safety of the study (see Section 6.6.5 of protocol). Details describing the DSMC process 
and procedures will be outlined in a separate DSMC Charter. 
 
Adverse events (AEs) will be collcctcd from time of informed consent and continue until 
30 days after the last study treatment is administered. Longer follow-up and collection of 
AEs may be required for patients that do not have an absolute neutrophil count (ANC) 
recovery within 42 days (i.e., until the recovery or the reason for no recovery is diagnosed) 
after the last induction or consolidation cycle. 
 
A flow diagram of the study design is shown in Figure 2---1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Date of Issue: 20 March 2018 
Cantex   Pharmaceuticals,  Inc.  Protocol  No.  CNTX-CX-0  I   2015  AML   I      Covance  Study  ID:  00000014620 I 
 
 
Figure 2---1 Study Design 
Abbreviations: AML=acute mycloid leukemia 
Note: It is expected that approximately 90 patients will be screened to identify 75 patients for 
randomization. 
 
2.6 Sample Size and Power 
 
A total of25 evaluable patients per arm will provide 71.8% power fi:ir each test comparing a dose with 
control via a Fisher's exact test at I-sided alpha 
00 0.15 to detect a difference between a control proportion 
0.55 and an experimental dose proportion 0.80; these tests will be conducted in a fixed sequence: higher 
dose versus control first and lower dose versus control second, with the second test considered 
exploratory (failed) if the first test fails. 
 
3 
EFFICACY AND SAFETY VARIABLES 
3.1 Primary Efficacy Endpoint(s) 
 
The primary endpoint is the rate of patients in each treatment group achieving morphological CR based on 
IWG criteria during the induction and re-induction phases or the treatment. Morphologic CR is defined as 
ANC >1000/;tL, platelet count>100,000/µL, <5% blasts in an bone marrow aspirate sample, no blasts 
with Auer rods, and no evidence of extramedullary disease (sec Appendix A of protocol). Note that a 
patient is only considered to have achieved morphologic CR if this is documented on or after 21 days 
from date of randomization and not superseded by a subsequent data entry within 42 days of 
randomization that indicates treatment failure or progressive disease or persistent disease as indicated by 
>5% blasts in a bone marrow aspirate sample. 
 
 
 
 
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Cantex  Pharmaceuticals,  Inc. Protocol  No. CNTX-CX-01  2015  AML  I     Covance Study  ID: 000000146201 
 
 
3.2 Secondary Efficacy Endpoints 
 
• 
Event Free Survival (EFS) 
o  Event-free survival (from date of randomization) is measured from the date of 
randomization until treatment failure (e.g., failure to achieve composite complete 
morphological remission during the induction or re-induction phase of the study lasting up 
to 60 days, relapse from CR, or death from any cause, whichever occurs first). 
 
 
• 
Leukemia-Free State (LFS) 
o  Leukemia-free survival is only assessed in patients who achieve composite CR and is 
measured from the date ofleukemia-free state until disease relapse or patient death from 
any cause, whichever occurs first. 
 
• 
Overall Survival (OS) 
o Overall survival is measured from the date of randomization until death from any cause. 
 
• 
Composite Complete Remissions (CR) rate 
o 
 Complete remission rate includes CR, (on or after 21 days from date of randomization) 
and CRi and CRp (either need to be on or after 21 days from date of randomization) as 
defined by IWG criteria (Appendix A in the protocol) during the induction and re- 
induction phases of treatment. If a patient achieves a composite CR, but followed by PD 
or treatment failure from day 21 to 42, then the patient did not achieve a composite CR 
and should be considered a treatment failure. 
 
• 
Duration of morphologic CR 
o  Duration of morphologic complete response is measured from the achievement of CR to 
detection of relapse. A relapse is defined as progressive disease or death from clinical 
disease progression 
 
• 
Duration of composite CR (if available) 
o Duration of composite complete response is measured from the date of achievement of 
composite CR to detection of relapse. A relapse is defined as either progressive disease or 
death from clinical disease progression. 
 
• 
30-day, 60-day and 90-day mortality 
o Thirty-day, 60-day, and 90-day mortality are the rate of death during 30 days, 60 days, and 
90 days, respectively, from the first day of induction treatment. 
 
 
• 
Neutrophil and Platelet Recovery 
o Time to neutrophil recovery (from date of randomization) is measured from the date of 
randomization until ANC recovers to> 500 and>1000/µL respectively. 
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Cantex  Pharmaceuticals, Inc.  Protocol  No. CNTX-CX-01  2015 i\ML  I     Covance Study  ID:  000000146201 
 
 
 
o  Time to transfusion-independent platelet recovery (from date of randomization) is 
measured from the date of randomization until the first day that the platelet count recovers 
to> 20,000 and>100,000/ tL respectively (provided it is not as a consequence of platelet 
transfi.1sion and provided platelets are then maintained at> 20,000 and >100,000/µL 
respectively for the five subsequent clays without platelet transfusion). 
3.3 
Safety Endpoints 
Key safety endpoints will be assessed by review of summaries of A Es which will include only treatment- 
emergent AEs (TEAEs), unless otherwise stated. Adverse events will be categorized  by  System  Organ 
Class (SOC) and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) 
dictionary (version 14.1), and will be graded according to NCI-CTCAE version 4.03. 
 
4 
PHARMACOKINETIC/PHARMACODYNAMIC VARIABLES 
Details to be provided by Biocascade in a separate PK SAP. 
 
5 
ANALYSIS POPULATIONS 
The analysis sets that will be used for statistical analyses are as follows: 
 
Intent-To-Treat (ITT): This includes all randomized patients. Patients will be analyzed according to the 
treatment to which they are randomized. The ITT Population will be the primary analysis set for the 
efficacy variables. 
 
modified-Intent-To-Treat (m!TT): This includes all randomized patients who received at least one dosage 
of study drug. Patients will be analyzed according to the treatment to which they are randomized. 
 
Per Protocol (PP): Supporting analyses will be conducted on the PP Population, comprising all patients 
randomized and treated without major protocol deviations during the trial. This population will he 
documented before final database lock. PP Population will be analyzed according  to the  treatment  lo 
which they received. 
 
 
The following are considered protocol deviations for the purpose of identifying the per protocol set: 
 
1. Patients who were subsequently found to be not complying with the inclusion and exclusion 
criteria 
2. Patients who are not compliant with study restrictions (eg. use of prohibited medication (generic 
drug name) or prohibited treatment therapy) 
3. Patients who continued in study but should have been withdrawn according to withdrawal criteria 
4. Patients who are not compliant with study drug treatment dose modification or stoppage rules 
(either temporary or permanent). 
5. Patients who took incorrect study drug (CX-01 or other) dose, frequency, timing or method of 
drug delivery (e.g. subject overdosed with study drug, incomplete study drug administered). 
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6. Patients who took different study drug than the study drug to which they were randomized. 
7. Patients who do not have post baseline data anywhere in the system. 
 
!terns I to 5 are routinely monitored in the study as part of the study monitoring plan. 
 
Safety: All patients who received at least one dose of study treatment. Patients will be included in the 
analyses according to the treatment they received. The Safety Population will be used  in the  analyses of 
all safety endpoints. 
 
 
6 
DATA HANDLING 
6.1 Time points and Visit Windows 
 
Day I is defined as the day of randomization visit. Relative days after Day I are calculated as (assessment 
date···· Day I  date)+  I.   Relative days prior to Day I  arc calculated  as (assessment date 
Day I date). 
The day prior to Day I is Day -1. 
All data will be analyzed using nominal study visits as defined in the Study Schedule and eCRF. No visit 
windows will he applied for summary and analysis. 
In determining the baseline, if assessment on date of randomization is unavailable, then the last scheduled 
or unscheduled assessment before first study drug/randomization will be used instead. 
6.2 Handling of Dropouts or Missing Data (where applicable) 
 
For ITT analysis,  patients with partial or missing data  to determine morphologic complete  remission  on  
the eCRF form will be considered as not having met the criteria morphologic complete remission. For PP 
analysis and elsewhere, only the complete cases will be analyzed and no missing value imputation will be 
carried out. 
 
Incomplete AE-rclatcd dates will be handled as follows: 
• In cases where: 
o the onset date is completely missing or 
o the onset is in the same year (only the onset year is available) as the start of study treatment 
or 
o the onset is in the same month and year (only the day is missing) as the start  of study 
treatment or 
o either the onset day or month is missing but the year is  not  before start of study treatment 
then the onset date will be replaced by the minimum of start of study treatment and AE resolution date. 
• In all other cases the missing onset day or onset month will be replaced by first day or January. 
 
 
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• Incomplete stopping dates will be replaced by the last day of the month (if the day is missing only), 
unless this will result in a date after the date of death. If the imputed date will exceed the date of death, 
the date of death will be used as the stopping date. No imputation is needed if the event is ongoing. 
• In all other cases the incomplete stopping date will not be imputed. 
 
To impute missing day of follow-up dates (such as safety long term follow up) or Disease History, the 
missing day will be taken as the 15th of the month, as long as month and year is available. In all other 
cases missing or incomplete dates will not be imputed. 
 
In patient listings, the documented  date from  cCRF will  be  reported  (e.g.  .May2016  in  case where the  
day is missing, but month and year are available). 
 
7 
STATISTICAL METHODS 
7.1 General Principles 
 
All data processing, summarization and analyses will be performed using the Hosted SAS Environment 
Version 9.3 (or later) of the SAS'° statistical software package. 
Unless specified otherwise, data will be displayed using the following treatment group labels, in the order 
presented: 
 
• 
Control, 
 
o those who are on Idarubicin + Cytarabine therapy only 
 
• 
Low CX-01, 
 
o those who are on ldarubicin + Cytarabine + plus lower dose CX-01 
 
• 
High CX-01, 
 
o those who are on Idarubicin + Cytarabine + plus higher dose CX-01 
 
• 
Overall 
 
All data collected will be presented in listings by treatment group, site, subject and visit (where 
applicable), unless otherwise specified. 
Data will be presented in snmmary tables by treatment group, and visit (where applicable). The category 
"Missing" will be presented if the number missing is greater than zero for at least one treatment group. 
Descriptive summary statistics for continuous variables will include the number of subjects (N), mean, 
standard deviation (SD), median and range. 
 
 
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Cantex  Pharmaceuticals,  Inc.  Protocol  No. CNTX-CX-01  2015  AML  I     Covance Study  ID: 000000146201 
 
 
Descriptive summary statistics for categorical variables (such as gender, race) will include frequency 
counts and percentages [n (%)]. Unless stated otherwise in the table shells, the denominator for 
percentage calculations for a particular variable will be the number of subjects with non-missing data. 
Dates will be displayed as DDMMMYYYY. 
All significance tests will be two-sided and use a 5% significance level except for primary outcome, 
which is tested at I -sided at 15% level of significance. 
 
7.2 Subject Disposition and Data Sets Analyzed 
Subject disposition will be listed and summarized by treatment group and overall and  will  include  the 
number and percentage of subjects: 
• 
screened; 
• 
randomized; 
• 
randomized and not treated; 
• 
treated; 
• 
available at each study visit (treatment period, 30 day safety follow-up, long term follow-up at every 3 
months until approximately 18 months or deaths of all patients, whichever is earlier); 
• 
included in each study population (ITT, PP, Safety). 
In addition, the number and percentage of subjects who complete the study and who discontinued early, 
including a breakdown of the primary reasons as reported in the eCRF for early  termination,  will  be 
presented for all analysis populations (ITT, PP, Safety).  Additional  summaries  frir  safety  follow  up 
(reasons for not completing safety follow up) and long term  follow  up (status  of  long  term  follow  up, 
cause of death recorded at long term  follow  up) will  be  provided  for each treatment  arm for the ]TT, PP  
and safety population. 
A summary of patient enrollment by site will also be provided by treatment group and overall for the ITT 
population. 
A summary of the reasons for screen failure as well as the number of subjects screened but not 
randomized will be produced. No other informati,ln for screen failures will be presented. 
 
7.3 Protocol Deviations 
 
All protocol deviations will be listed and summarized by treatment group for the ITT population. 
All important protocol deviations leading to exclusion from the  PP  population  (see  Section  5)  will  be 
listed and summarized by treatment group for the ITT population. 
 
 
 
 
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Cantex  Pharmaceuticals, Inc.  Protocol  No. CNTX-CX-01  2015  J\ML  I     Covance  Study  ID: 000000146201 
 
 
7.4 
Demographics and Other Baseline Characteristics 
 
Demographic and baseline characteristics will be listed  and  summarized  by  treatment  group and  overall 
for all analysis populations (ITT, PP, Safety). Standard descriptive statistics will be presented for the 
continuous variables of: 
• 
Age at screening (years) [calculated as (informed consent date - date of birth)/365.25 and 
reported as whole years; 
• 
weight (kg); 
• 
height (cm); 
• 
BMI 
• 
Time since diagnosis 
• 
Baseline blasts in bone marrow(%) 
• 
Baseline LDH 
The total counts and percentages of' subjects will be presented for the categorical variables of: 
• 
age group (years) (grouped as <70 and 2: 70); 
• 
sex; 
• 
race; 
• 
ethnicity; 
• 
AML type (de novo or secondary); 
• 
Baseline peripheral blasts (Yes/No) 
• 
ECOG performance status 
• 
Time since diagnosis(<= 30 days,> 30 days) 
 
 
No formal tests of statistical significance will be performed on the demographic and baseline data. 
Other baseline measurements, such as bone marrow aspirate/biopsy, pregnancy test result, lab parameters, 
vital signs, ECG and ECOG, will be summarized by treatment group with the post-baseline measurements. 
7.4.1 
Medical History 
Medical history will be coded using the latest available Medical Dictionary for Regulatory Activities 
(MedDRA). All medical history will be listed, and the number  and  percentage  of  subjects  with  any 
medical history will be summarized for some analysis populations (ITT, Safety) by system  organ  class  
(SOC) and preferred term (PT) for each treatment group and overall. 
 
 
 
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7.4.2 
Prior, Post treatment (anti AML) and Concomitant Medications 
Medications received prior to or concomitantly with treatment will be coded using  the  WHO  Drug 
Dictionary [March 2016 132 version] Anatomical Therapeutic Chemical (ATC) Classification codes. 
Prior, post treatment medications and concomitant medications are defined as follows: 
• 
Concomitant medications are those with a start date on or after the first dose date of study 
treatment,, or those with a start date before the first dose date of study treatment and a stop date on 
or after the first dose date of study treatment. 
• 
Prior medications will be defined  as non-study  medication  with  a  stop date prior to the first  dose  of 
study treatment. 
• 
Post treatment medications are those with start date after the last dose of study drug. 
Concomitant medications will be further divided according to whether they were started before (both prior 
and concomitant) or after (concomitant-only) the first dose of treatment. 
If a medication cannot be classified as "prior" or "concomitant" after applying imputation rules for 
missing/incomplete dates, it will be classified as concomitant. 
Prior anti-AML treatment medications and concomitant medications will be listed  and  summarized 
separately for ITT analysis population. Post treatment medications will be listed only. 
The number and percentage of subjects using each medication will be displayed together with the number 
and percentage of subjects using al least one medication within each therapeutic class (ATC-Level 2), 
chemical subgroup (ATC-Level 4), and generic term. 
 
 
7.5 Measurements of Treatment Exposure and Study Drug Usage Rate 
 
Extent of study treatment exposure will be summarized for the entire study treatment period and by cycle. 
Exposure variables will include duration of study treatment, number of dose reductions, number of 
treatment delays (interruptions), number of treatment cycles, and dose intensity relative lo dose levels 
specified in the protocol. 
 
 
There are three types of treatment cycles: induction cycle, re-induction and consolidation cycles. For each 
cycle, the exposure for each drug (Jdarubicin, Cytarabine, CX-01) is taken as the sum of duration of drugs 
for drug taken within that cycle. For drugs that started and ended on the same day, it will be regarded as I 
day, for drugs that started and ended on difforenl days, the duration will be calculated as date of last dose 
minus date of first dose + 1 day for the period which the drug was administered. Proportion of patients 
who are exposed to the full expected duration for each component of the study drug will be presented for 
each cycle. 
 
 
The study drug usage rate calculation for the induction cycle is as follows, where the expected number of 
days is the number of days the patients were expected to take the drug, up lo the point of study 
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discontinuation. If a patient was scheduled to lake 7 days of drug but only took the drug for 5 days 
because of early withdrawal, then the expected number of days would be 5. 
 
The calculation of BSA will be based on the  best  possible  results for study  drug  usage (closest  to 100% 
and below) from Mostellar, Dubois and Gehm, formulae as outlined below. 
 
DuBois[ I] 
BSA ( 111 ) = 0.007184 x Height(cm) 0 725 x Weight(kg) 04 25 
 
 
Gehan/2]: 
BSA (1112) =, 0.0235 x lle ight(cm) 04 2246 x Weight(kg) 0 514 56 
 
Mostellar/3]: 
BSA 
2 
(111 ) = ([Heigh!(cm) x Wcight(kg) ]/ 3600)0 5 
 
 
Group I: ldarubicin + Cytarabine 
 
Idarubicin: 
 Actual total dosage per 1112/( 12 mg/1112 x expected number of days) [Maximum expected number of 
days=3] 
Cytarabine: 
 Actual total dosage per 1112/( I 00 mg/1112 x expected number of days) [Maximum expected number of 
days=7] 
 
Group 2: ldarubicin + Cytarabinc + plus lower dose CX-01 
 
Initial CX-01 4 mg/kg, (0 or 100%) 
CX-0 I: 
 Actual total dosage per kg/(3 mg/kg/dayx expected number of days) [Maximum expected number of 
days=7] 
ldarnbicin: 
 Actual total dosage per 1112/( 12 mg/1112 x expected number of days) [Maximum expected number of days,-
3] 
Cytarabine: 
 Actual total dosage per 1112/( I 00 mg/1112 x expected number of days) [Maximum expected number of 
days=7] 
 
Group 3: ldarubicin + Cytarabinc + pins higher dose CX-01 
 
Initial CX-01 4 mg/kg, (0 or 100%) 
CXOl: 
 Actual total dosage per kg/(6 mg/kg/dayx expected number of days) [Maximum expected number of 
days=7] 
 
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·-· 
- . 
·-- 
Canlcx Pharmaceuticals, Inc, Protocol No, CNTX-,(:X-01 2015 /\ML I Covance Study ID: 000000146201 
 
 
Idarubicin: 
 Actual total dosage per 1112/( 12 mg/1112 x expected number of days) [Maximum expected number of 
days=3] 
Cytarabinc: 
 Actual total dosage per 1112/(100 mg/1112 x expected number of days) [Maximum expected number of 
days=7] 
 
The study drug usage rate calculation for the re-induction cycle under 5+2 regimen is as follows: 
 
Group 1: ldarubicin + Cytarabinc 
 
Idarubicin: 
 Actual total dosage per 1112/ (12 mg/1112 x expected number of days) [Maximum expected number of 
days 0 0 2] 
Cytarabine: 
 i\ctual total dosage per 1112/ ( I 00 mg/1112 x expected number of days) [Maximum expected number of 
days=5] 
 
Group 2: ldarubicin + Cytarabinc + plus lower dose CX-01 
 
Initial CX-01 4 mg/kg, (0 or 100%) 
CXO 1: 
Actual total dosage per kg/(3 mg/kg/day x expected number of days) [Maximum expected 
number of days=S] 
Jdarubicin: 
Actual  total  dosage per 1112/ (12 mg/1112 x expected number of days) [Maximum expected 
number of days=2] 
Cytarabine: Actual total dosage per 1112/ (100 mg/m2  x  expected  number  of  days)  [Maximum  expected 
number of days=5] 
 
Group 3: Idarubicin + Cytarabinc + plus higher dose CX-01 
 
Initial CX-01 4 mg/kg, (0 or 100%) 
CXOJ: 
Actual total dosage per kg/ (6 mg/kg/dayx expected number of days) [Maximum expected 
number of days=5] 
ldarubicin: 
Actual total dosage per 11121 (12 mg/1112 x expected number of days) [Maximum expected 
number of days=2] 
Cytarabine: Actual total dosage per 1112/ (100 mg/m2 x  expected  number  of  days)  [Maximum  expected 
number of days=5] 
 
The study drug usage rate calculation for the consolidation cycle is as follows: 
 
 
 
 
 
 
 
COVANCE INC. CONFIDENIJAL 
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ST AD-008 version 02 


2
Statistical  Analysis Plan 
Version: Final 
Date of  Issue: 20 March 2018 
 
Cantcx  Pharmaceuticals, Inc.  Protocol  No. CNTX-CX-01  2015  AML  I     Covance Study  ID: 000000146201 
 
 
Group 1: Cytarabinc 
 
Cytarabine: Actual total dosage per m2/ (2 g/ m2x expected number of days) [Maximum expected 
number of days=3] 
Group 2: Cytarabine + plus lower dose CX-01 
 
Initial CX-01 4 mg/kg, (0 or 100%) 
CXOJ: 
Actual total dosage per kg/(3 mg/kgx expected number of days) [Maximum expected 
number of days=5] 
Cytarabine: Actual total dosage per 1112/(2 g/ rn2x expected  number  of  days)  [Maximum  expected  
number of days=3] 
 
Group 3: Cytarabinc + plus higher dose CX-01 
 
Initial CX-01 4 mg/kg, (0 or 100%) 
 
CXOI: 
Actual total dosage per kg/(6  mg/kgx  expected  number  of  days)  [Maximum  expected 
number of days-,5] 
Cytarabine: Actual total dosage per 
of days=3] 
111 /(2 g/ nix expected number of days) [Maximum expected number 
 
7.6 
Efficacy 
7.6.1 
Primary Efficacy Analysis 
Fisher exact test will be used to compare the proportion of CRs between each dose and control for the ITT 
population using one sided test at 15% level of significance along with a 70% CI. These tests will be 
conducted in a fixed sequence: higher dose versus control first and lower dose versus control second, with 
the second test considered exploratory (failed) if the first test fails. 
 
7.6.2 
Secondary Efficacy Analysis 
 
The primary efficacy analysis will be repeated using the PP Population as a supportive analysis along 
with CRi and composite CR for ITT and PP. Complete response rates and composite complete response 
rates and confidence intervals will also be reported for key subgroups (De-novo vs secondary AML at 
diagnosis, Age< 70 vs Age 2 70, ECOG performance status:::: 1 vs ECOG performance status =2). The 
following secondary analyses will be performed on the ITT population. Analyses of EFS, LFS, time to 
neutrophil and platelet recovery, and OS will be descriptive. Kaplan-Meier (KM) estimates will be used to 
estimate the survival distribution for each arm and KM plots will be produced to accompany these 
analyses. 95% Confidence Intervals will be reported for medians and KM estimates. Duration of response 
will be analyzed using a similar approach; the survival distributions will be estimated as cumulative 
incidence functions. 
COVANCE INC. CONFIDEN71Al 
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Statistical  Analysis Plan 
Version: Final 
Date of Issue: 20 March 2018 
 
Cantcx  Pharmaceuticals, Inc. Protocol  No. CNTX-CX-0 I  20 I 5 AML  I     Covance Study  ID: 00000014620 I 
 
 
 
M01iality rate at Day 30, Day 60, and Day 90 will  be reported  using descriptive statistics in a manner 
similar lo the reporting of the morphologic CR rate. The time to neutrophil and platelet recoveries will be 
reported using the following descriptive statistics: N, mean, SD, median, minimum, maximum, and the 1st  
and 3rd quartiles. 
 
7.6.3 
Sensitivity Analysis 
None. 
7.6.4 
Subgroup Analysis 
Descriptive statistics for the primary efficacy variable (CR) and composite CR and 95% confidence 
intervals will be provided of the following subgroups for ITT population provided there is suflicient 
number of patients in total within the subgroup across the treatment arms: 
 
• 
Age groups (<70 and 2: 70) 
• 
AML at diagnosis (de novo, secondary) 
• 
ECOG performance status (:S 1 Vs ECOG=2) 
 
 
7.6.5 
Exploratory Analysis 
 
Additional efficacy analyses will be performed as exploratory analysis for the following variables, 
summarized by treatment groups and analyzed in the same way as secondary analyses above. 
 
 
• 
Duration of composite CR (if present) 
 
• 
Days until neutrophil recovery to 2: 500/ LL (from date of randomization and from date of first 
study drug) 
 
• 
Days until platelet recovery to 2: 20,000/ LL (from date of randomization and from date of first 
study drug) 
7.7 
Safety 
7.7.1 
Adverse Events 
All adverse events (AEs) recorded on the eCRF will he coded using the MedDRA dictionary [Version 
14. l] and classified as either pre-treatment AEs or treatment - emergent AEs (TEA Es) as follows: 
• 
Pre-treatment AEs arc events that staii prior to the date of first dose of study treatment. 
• 
Treatment-emergent AEs (TEAEs) arc events with start date and time on or after the date and 
time of first dose of study treatment (and up to 30 days after date of last dose of treatment) with 
 
COVANCE INC. CONFIDENT/AI. 
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s·r-AJ)-008  version 02 


Statistical  Analysis Plan 
Version: Final 
Date of Issue: 20 March 2018 
 
Cantex  Pharmaceuticals, Inc. Protocol  No. CNTX-CX-0 I  2015 AML   I     Covance Study ID: 00000014620 I 
 
 
start dale prior to the dale of first dose of study treatment whose severity worsens on or after the 
dale and time of first dose of study treatment. 
Assessment of AE severity will be based on the National Cancer Institute-Common Terminology Criteria 
for Adverse Events (NCI-CTCAE, version 4.0.3). 
All AF data will be listed by treatment group including Pre-treatment AEs and TEAEs. The number and 
percentage of subjects reporting each treatment AE and TEAEs will be  summarized  for  each  treatment 
group and overall, by System Organ Class (SOC)  (sorted  alphabetically) and  Preferred  Term  (PT) (sorted 
by descending overall total) for Safety populations. 
In addition, corresponding listings of serious AEs (SAEs), AEs leading to discontinuation of treatment, 
AEs causing interruptions from study treatment, AEs causing dose reduction from study treatment and 
study treatment-related AEs causing dose reductions are provided. 
An overview table will summarize the number and percentage of subjects with at least one of the 
following AEs/TEAEs, where subjects with more than one AEs/TEAE in a particular category are 
counted only once in that category: 
• 
any AE; 
• 
any TEAEs; 
• 
treatment-related TEAE; 
• 
any AE by maximum NCl-CTCAE grade;treatment-related TEAE by maximum NCJ-CTCAE 
grade; 
• 
AE leading to treatment interruption; 
• 
treatment- emergent AEs leading lo treatment interruption; 
• 
AF leading to treatment reduction; 
• 
treatment- emergent AEs leading to treatment reduction; 
• 
AE leading lo treatment discontinuation; treatment-emergent AEs leading to discontinuation 
from the study; 
• 
SAE; 
• 
treatment-emergent SAE; 
• 
SAE leading to death; 
• 
treatment-emergent SAE leading to death; 
• 
SAE leading to treatment discontinuation; 
The number and percentage of subjects reporting each TEAE will be summarized by System Organ Class 
(SOC) and Preferred Term (PT) for the Safety population. Tables will be sorted alphabetically by SOC. 
!'Ts will be sorted by descending overall total; if  the  number  and  percentage  are the  same  for  different 
PTs, the PTs will be listed in alphabetical order (within the SOC). The following summaries  will  be 
produced: 
 
COVANCE INC. CONFIDENTIAL 
Page 24 of 34 
ST-AD-008 version 02 


Statistical  Analysis Plan 
Version: Final 
Date of  Issue: 20 March 2018 
 
Cantcx   Pharmaceuticals,  Inc.   Protocol   No.  CNTX-CX-01   2015  AML   I      Covance  Study  ID: 000000146201 
 
 
• 
TEAEs by SOC and PT; 
• 
TEAEs by PT;NCI-CTCAE Grade 3 or higher TEAEs by SOC and PT; 
• 
NCI-CTCAE Grade 2 or lower TEAEs by SOC and PT; 
• 
TEAEs related to treatment, by SOC and PT; 
• 
TEAEs by maximum NCl-CTCAE grade, by SOC and PT; 
• 
Treatment--related TEAEs by maximum NCI-CTCAE grade, by SOC and PT; 
• 
TEAEs causing discontinuation from treatment, by CTCAE and worst CTCAE grade; 
• 
TEAEs related lo treatment causing discontinuation from treatment, by CTCAE and worst CTCAE 
grade; 
• 
Serious TEAEs, by SOC and PT; 
• 
NCI-CTCAE Grade 3 or higher Serious TEAEs, by SOC and PT; 
• 
NCI-CTCAE Grade 2 or lower Serious TEAEs, by SOC and PT; 
• 
Serious TEAEs related lo treatment by CTCAE and worst CTCAE grade; 
• 
TEAEs leading to death, by SOC and PT 
In the above summaries, subjects with more than one AE/TEAE within a particular SOC are counted only 
once for that SOC. Similarly, subjects with more than one AE/TEAE within a particular PT are counted 
only once for that PT. For summary by maximum severity, subjects with multiple AE/TEAEs within a 
particular SOC or PT will be counted under the category of their most severe AE/TEAE within that SOC 
and PT. 
 
7.7.2 
Laboratory Evaluations 
Clinical laboratory assessments will be summarized using frequency tables, shift tables, and descriptive 
statistics. Frequency tables and shill tables will be presented by NCI-CTCAE grade. Laboratory variables 
with no NCI-CTCAE group will be presented in shift tables with respect to normal range. All laboratory 
variables will be presented in tables of descriptive statistics (mean, SD, etc.) and graphs will be presented 
for PT/INR, aPTT, anti-factor Xa, fibrinogen, D-dimcr, and platelet count. 
 
7.7.3 
Vital Signs and ECOG performance status 
Vital signs variables and ECOG performance status will be summarized using descriptive statistics at 
screening visit and start of consolidation cycle (vital signs only). 
7.7.4 
Electrocardiograms 
Counts and proportion  of patients with  clinically  significant  abnormal  results at screening and  Day 7 will 
be reported. 
 
 
 
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s·r /\1) 008 version 02 


Statistical  Analysis Plan 
Version: Final 
Date of  Issue: 20  March 2018 
 
Cantcx  Pharmaceuticals, Inc. Protocol  No. CNTX-CX-0 I  20 I 5 AML  I    Covance Study  ID: 000000 I 4620 I 
 
 
7.8 Interim Analysis 
A Data Safety Monitoring Committee (DSMC) will be instituted for this study according to a separate 
DSMC Charter in order to ensure ongoing safety of study subjects. 
 
No other interim analysis is planned. 
 
8 
CHANGES FROM PLANNED ANALYSES IN PROTOCOL 
 
A new analysis population m!TT is added as per client request aner the first DSMB meeting. 
 
For primary objective, the time component required (on or after 21 days from date of randomization) for 
the recognition of morphologic CR is added in the definition. 
 
For secondary objective, the time component required (on or after 21 days from date of randomization) 
for the recognition of CRi and CRp is added in the definition. 
 
For secondary and exploratory objectives, the following variables are additional to the protocol: 
 
• 
Duration of composite CR, with the definition of composite CR being clarified as CR or CRi or 
CRp. 
• 
Days until neutrophil  recovery  to 2: 500/ ,tL 
• 
Days until platelet  recovery  to 2: 20,000/ ,tL 
 
For Leukemia-Free State (LFS), the definition is now changed to from date ofleukemia free state, 
because the protocol definition from date of randomization is not correct. 
 
Repeat ofCRi and composite CR in the same fashion as primary efficacy analysis and addition of 
composite CR for subgroup analysis. 
 
Compliance is termed as study drug usage rate in the SAP. 
Competing risk of death analyses will not be performed. 
Post treatment medications will only be listed and not summarized as per client request. 
 
9 
DATA ISSUES 
Not applicable. 
 
10 REFERENCES 
 
[I] DuBois D, DuBois DF. A formula to estimate the approximate surface area if height and weight be 
known. Arch Int Med 1916;17:863-71. 
 
COVANCE INC. CONFWENT/AL 
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ST-/\D-008 version 02 


Statistical  Analysis Plan 
Version: Final 
Date of  Issue:  20 March 2018 
 
Cantex  Pharmaceuticals, Inc. Protocol  No. CNTX-CX-0 I  20 I 5   AML  I    Covance Study ID: 000000 I 4620 I 
 
 
12] Gchan EA, George SL. Estimation of human body surface area from height and weight. Cancer 
Chemothcr Rep l 970;54:225-35. 
 
[3] Mosteller RD. Simplified calculation of body-surface area. N Engl .I Med 1987;3 l 7: I 098. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVANCE INC. CONFIDENT/ii/. 
Page 27 of 34 
ST /\D-008 version 02 


 
Version: Final 
Statistical Analysis Plan 
 
Date 9_f lssue: 20 March 201Jl 
Cantex  Phannaceuticals, Inc, Protocol  No, CNTX-CX-0 I  20 J 5 AML J 
Covance Study ID: 000000 J 4620 J 
 
11 APPENDICES 
 
Appendix I- Schedule of Events 
Table 11-1 Induction/Re-induction Cycle Schedule of Study Procedures 
 
 
Examination 
Scree 
n  
Visit 
D 
-28- 
1 
DI 
D2 D3 D4 
DS 
D6 
D7 
D 
8-13 
D 
14-21 
At count 
recovery 
&   
Weekly 
from 
D21 
until 
count 
recovery 
Early 
Term Visit 
Safety FU visit 
(30 days after 
last dose of 
treatment) 
Long 
Term 
FU 
contact 
(every 
3 month 
sup to 
death, or 
EoS) 16 
or D6015 
Informed consent1 
X 
Demographic and 
medical history 
X 
Eligibility criteria 
X 
X 
Randomization 
X 
Idarubicin 2 
X 
X 
X 
Cytarabine3 
X 
X 
X 
X 
X 
X 
X 
CX-01 Bolus4 
X 
CX-015 
continuous 
infusion 
X 
X 
X 
X 
X 
X 
X 
ECOG status 
X 
Vital signs (BP, 
X 
 
COVANCE INC. CONFIDENTIAL 
Page 28 of 34 
ST-AD 00S version 02 


 
Version: Final 
Statistical Analysis Plan 
 
Date of Issue: 2J)_March 201_!l 
Cantex Pharmaceuticals, Inc. Protocol No. CNTX-CX-01 2015 AML I 
Covance Study ID: 00000014620 I 
 
Table 11 1 Induction/Re-induction Cycle Schedule of Study Procedures 
 
 
Examination 
Scree 
n  
Visit 
D 
-28- 
1 
DI 
D2
D3
D4 
D5
D6
D7 
D 
8-13
D 
14-21 
At count 
recovery 
&   
Weekly 
from 
D21 
until 
count 
recovery 
or D6015 
Early 
Term Visit 
Safety FU visit 
(30 days after 
last dose of 
treatment) 
Long 
Term 
FU 
contact 
(every 
3 month 
sup to 
death, or 
EoS) 16 
heart rate, height 
and weight)6 
Physical exam 
X 
12-lead ECG 
X 
X 
Echocardiography 
orMUGAscan 
X 
Hematology7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-factor Xa, 8 9 
X 
X 
X 
X 
X 
X 
X 
X 
x9 
X 
PT/INR, aPTT8 10 
X 
X 
X 
X 
X 
X 
X 
X 
xio 
X 
X 
X 
X 
Chemistry 11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK sampling12 
X 
X 
AE Assessment 
Continuously 
  
, '  
Previous 
medications 
X 
! 
I 
I 
i 
I 
i 
I 
I 
! 
i i 
i 
I 
! I 
I 
! 
I 
Concomitant 
medications 
continuously 
, ' 
COVANCE INC. CONFIDENTIAL 
Page 29 of34 
ST-AD-008 version 02 


 
Version: Final 
Statistical Analysis Plan 
 
Date of 1$!Qe: 20 Marrl!_ 2018 
Cantex Pharmaceuticals. Inc. Protocol No. CNTX-CX-0!  20!5 AML I 
Covance Study ID: 000000146201 
 
Table 11-1 Induction/Re-induction Cycle Schedule of Study Procedures 
 
 
Examination 
Scree 
n  
Visit 
D 
-28- 
1 
DI 
D2 D3 D4 D5 D6 
D7 
D 
8-13 
D 
14-21 
At count 
recovery 
&   
Weekly 
from 
D21 
until 
count 
recovecy· 
or D6015 
Early 
Term Visit 
Safety FU visit 
(30 days after 
last dose of 
treatment) 
Long 
Term 
FU 
contact 
(every 
3 month 
sup to 
death,or 
EoS) 16 
Fibrinogen, 
D-dimer 
X 
X 
X 
X 
Serum or urine 
pregnancy test13 
X 
X 
Bone marrow 
aspirate/ 
Biopsy14 
x14 
xi4 
x14 
Relapse and 
survival data 
X 
 
Abbreviations: AE=adverse event, ALT=alanine aminotransferase, ANC=absolute neutrophil count, anti-Xa=anti-factor !0a, 
aPTT=activated partial thromboplastin time, AST=aspartate aminotransferase, BP=blood pressure, BUN=blood urea nitrogen, 
CBC=complete blood count_ CX-01=2-O, 3-0 desulfated heparin, D=day, ECG=electrocardiogram, ECOG=Eastern Cooperative 
Oncology Group. EoS=end of study, FU=follow-up, INR=international normalized ratio, IV=intravenous, LDH=lactate dehydrogenase, 
MUGA=multi gated acquisition. OS=overall survival, PK=pharmacokinetics, PT=prothrombin time, Term=termination. 
 
l. 
Informed consent must be obtained before any study-related procedures are conducted. 
 
COVANCE INC CONFIDENTIAL 
Page  30 of34 
ST-AD-008 version 02 


 
Version: Final 
Statistical Analysis Plan 
 
Date Qflssue: 2JLMarch 201 
Cantex Pharmaceuticals, Inc. Protocol No. CNTX-CX-0 I 2015 AML I 
Covance Study ID: 00000014620 I 
 
2. 
Idarubicin administered at a dose of 12 mg/m2/day by slow (10 to 30 minutes) lV injection/infusion daily on Days 1, 2, and 3. 
3. 
Cytarabine administered at a dose of 100 mg/m2/day as a continuous 24-hour IV infusion on Days 1-7. Patients who do not 
achieve leukemia-free state (<5% bone marrow blasts) on bone marrow aspirate performed between Days 14-21 may receive a re- 
induction cycle with the same regimen ("7 + 3" ± CX-01). Ifin the Investigator's opinion, the patient is not fit to receive full re- 
induction cycle of"7 + 3" ± CX-01, at the Investigator's discretion the patient may receive "5 + 2" ± CX-01 which is 5 days of 
cy1arabine (Days 1-5) and 2 days of idarubicin (Days 1 and 2). 
4. 
CX-01 administered at a dose of 4 mg/kg as an initial bolus on Day l only, 30 minutes after completion of administration of the 
first dose of idarubicin. 
5. 
CX-01 administered at a dose of 0.125 or 0.25 mg/kg/hour as a continuous 24-hour IV infusion on Days 1-7. 
6. 
Height obtained at Screening only. Actual body weight will be measured at the beginning of each cycle to calculate treatment 
doses. 
7. 
Hematology must include the following: hemoglobin, ANC, and platelets. All other hematology assessments should be performed 
only if standard of care and/or clinically indicated. Hematology samples will be collected daily until discharge and weekly 
thereafter until recovery. 
8. 
Note: blood samples for PT/INR, aPTT and anti-Xa levels will be collected 12 hours after the bolus dose ofCX-01. 
9. Anti-Xa samples ,vill be collected only on Days 1-8. 
Io. PT/aPTT will be collected daily on Days 1-8, and on Day 9, Day 1 L and Day 13. 
11. Chemistry (and comprehensive metabolic panel) includes BUN, serum creatinine, total bilirubin, ALT, AST, and alkaline 
phosphatase. Samples will be collected daily until discharge. 
12. At selected sites, blood samples for steady-state PK analysis will be collected during the induction cycle from the first six 
randomized patients assigned to CX-01 on Days 3 and 5 at a single time point. 
13. For females of childbearing potential only. All female patients will have a urine pregnancy test at Screening; positive urine tests 
must be confirmed by a serum pregnancy test. 
14. Bone marrow aspirates and/or biopsies are not performed weekly. If the patient's peripheral blood is negative for persistent AML: 
a bone marrow aspirate and/or biopsy will be performed (once) between Days 14-21 to determine the need for re-induction. Bone 
marrow biopsy may be necessary if sufficient spicules are not available on aspirate. Bone marrow aspirate at baseline and follow- 
up should include analysis by flow cy1ometry and cytogenetic analysis. Bone marrow (or peripheral blood if bone marrow is 
unavailable) should be sent to the institution's local cy1ogenetic laboratory for analysis. For patients with documented CR, 
confirmatory bone marrow aspirate slides will be submitted to the Sponsor or designee. If count recovery has not occurred by Day 
42, a bone marrow aspirate/biopsy will be performed to evaluate disease status, unless presence of persistent AML in peripheral 
blood. 
COVANCE INC. CONFIDENTIAL 
Page  31 of34 
ST-AD-008  version 02 


 
Version: Final 
Statistical Analysis Plan 
 
DaJeof Issue: 21:l_iVlarch 201_1! 
Cantex Pharmaceuticals, Inc. Protocol No. CNTX-CX-01 2015 AML 1 
Covance Study JD: 000000146201 
 
15. Count recovery is defined as ANC of> 1000/µL and a platelet count>100,000/µL. 
16. During long term follovi-up, relapse and survival data will be collected every 3 months until death or until the end of study. The 
end of study will occur approximately 18 months after the last patient is randomized. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVANCE INC. CONFIDENTIAL 
Page 32 of 34 
ST-AD-008 version 02 


Statistical Analysis Plan 
...:Y..::ec:_rs::..:i_:::m:::i:c.:Fci-'_:,n:::al:  
Datc of Issue: 20 March 2018 
Cantcx Pharmaceuticals, Inc. Protocol No. CNTX-CX-0 I 2015 AML I 
Covance Study ID: 00000014620 I 
 
 
 
Table 11-2 Consolidation Cycle Schedule of S'  tud-y Procedure.s 
 
 
 
- 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: aPTr-"activated partial thromboplastin time, anti-Xa=anti-factor IOa, BP00     blood pressure; 
CBC=complcte blood count, D=day, INR=international normalized ratio, PT=prothrombin time. 
1. Hematology must include the following: hemoglobin, ANC, and platelets. All other hematology 
assessments should be performed only if standard of care and/or clinically indicated. Hematology 
samples will be collected daily until discharge and weekly thereafter until recovery. 
2. PT/aPTT and anti-Xa blood samples will be collected 12 hours alter the bolus dose of CX-01. 
3. Chemistry (and comprehensive metabolic panel) will be collected daily until discharge. 
4. Actual body weight will be measured at the beginning of each cycle to calculate treatment doses. 
5. Cytarabine administered at a dose of 1.0 g/m2 over 3 hours, every 12 hours on Days 1, 3, and 5. 
6. CX-01 administered at a dose of 4 mg/kg as an initial bolus on Day 1, 30 minutes after completion 
of the first 3-hour infusion of cytarabinc, followed immediately by a continuous CX-01 24-hour 
IV infusion. 
7. CX-01 administered at a dose of 0.125 or 0.25 mg/kg/hour as a continuous 24-hour IV infusion on 
Days 1-5 for a total of 120 hours of continuous CX-01 infusion. 
8. Count recovery is defined as ANC of> 1000/µL and a platelet count>100,000/ tL. 
9. Bone marrow aspirate/biopsy is not done weekly. If the patient's peripheral blood is negative for 
persistent AML and count recovery has not occurred by Day 42 (of Consolidation cycle), a bone 
marrow aspirate/biopsy will be done to evaluate disease status. 
 
 
COVANCE INC. CONFIDEN71AL 
Page 33  of 34 
ST-AD-008 version 02 
Examination 
I) 
1 
I) 
2 
I) 
3 
I) 
4 
I) 
5 
Weekly 
from D6 
until 
count 
recover 
y8 
Hematology 1 
X 
X X
X X 
X 
PT/lNR, aPTT, and anti-X a2 
X 
X X
X X 
Chemistry3 
X 
X X
X X 
X 
Vital signs (BP, heart rate, height and weight)4 
X 
Cytarabine 5 
X 
X
X 
c·X-01 Bolus 6 
X 
CX-01 7 continuous infusion 
X 
X X
X X 
Concomitant medications 
continuously . 
, 
Adverse events 
  
continuously 
 
Bone marrow aspirate/ 
Biopsy 
x9 


Statistical  Analysis Plan 
Version: Final 
Date of Issue: 20 March 2018 
 
Cantcx Pharmaceuticals, Inc. Protocol No. CNTX-CX-01 2015 AML I 
Covance Study ID: 00000014620 I 
 
 
Appendix 11 - Table, Figure and Listing Shells 
 
The tabk, figure and listing shells and correspondingTable of Contents.are available as a separate file. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVANCE INC. CONFIDENTIAL 
Page 34 of 34 
ST-/\D-008 version 02 


 
 
 
TABLES, FIGURES, AND LISTINGS SHELLS 
 
 
A Randomized, Phase II Study of CX-01 Combined With Standard Induction 
Therapy for Newly Diagnosed Acute Myeloid Leukemia 
 
 
TFL Status:  Final 
TFL Date:  20 I 8-03-08T07:32:05 
Study Drug: CX-0 I 
Sponsor Reference: 
Covance Study  No: 00000014620 I 


Statistical Analysis flJan 
CNTX-CX-01-2015-AML- I 
Final 
 
 
 
 
l. 
INTRODUCTION 
The table, figure, and listing (TFL) shells presented in this document arc mock-ups 
and may be subject to minor format modifications once the actual data are used. 
The data represented in this document arc used for example purposes only and do 
not reflect the actual study data captured. The overall contents in any individual 
TFL shell will not change, although additional tables may be added if necessary, 
thus changing the table number scheme. Significant changes will be approved by 
the responsible Covance Clinical Pharmacology project team member and 
communicated lo the Sponsor. 
 
 
1.1 
General Programming Specifications 
 
All TFLs will follow the following rules: 
 
Papersizc will be A4, with the following margins in Inches: 
 
Landscap 
top 
1.5 
!en 
bottom 
1.73  right 
 
Portrait 
 
Top 
1.5 
!ell 
1.5 
Bottom 
1.5   right   1.23 
 
 
Every TFL will have a footnote containing program  location,  name, run date and 
run time (optional), listing source, the name of the last person  who  ran  the 
program, and the status of the output: Dry  run -  Draft-- Final  Draft- Final  (others 
as needed) 
 
Dates will be presented in the format yyyy-mm-dd 
The presentation order of the statistics will be: 
Mean, SD, median, minimum, maximum, N. The abbreviations Med, Min, Max 
may be used, if necessary. 
Rules for significant digits in safoty data tables arc as follows: if the raw value has  
x decimal places, then the mean and the median will have x decimal places, the 
standard deviation will have x+I decimal places. 
 
N will be presented as whole numbers. 
 
 
1.2 
Derived Parameters 
 
 
 
 
 
 
Document Version: 2018-03-08'1'07:32:05 
Page 2 of 105 


Statistical J\na!ysis Plan 
CNTX-CX-01-2015-i\ML-I 
Final 
 
 
 
 
Individual derived parameters (e.g. pharmacokinetic parameters) and appropriate 
summary statistics will be reported to three significant figures. 
 
1.3 
Tables Summarizing Categorical Data 
 
Tables that summarize categorical data will be created per these specifications: 
I. If the number of events is zero, data will be presented as "0". 
2. If the categories ofa parameter are ordered, all categories between the 
maximum possible category and the minimum category will be included, 
even iftF0 for a given category. 
3. If the categories arc not ordered, only those categories for which there is at 
least one subject represented will be included. 
4. A "missing" category will be included for any parameter for which 
information is missing. This will ensure that the population size totals are 
consistent across different parameters. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Page 3 of 105 


Statistical Analysis Plan 
CNTX-CX-01-2015-AML-1 
 
Final 
 
 
 
 
 
2. 
TJ:.BLE Cf CC?<)'?SN'IS 
 
 
 
Tabk: 14.1.2.l 
Table 14. l.2.2 
Table 14. l.2.3 
Table 14.1.2.4 
Table 14.1.2.5 
Table 14.1.2.6 
Table 14.1.2.7 
Table 14.l 2.8 
Table 14 1.2.9 
Table 14.1.2.10 
Table 14.1.2.11 
Table 14.1.2.12 
Table 14.1.6 
Table 14. l.7 
Table 14.l.8 
Table 14. t .9 
Table !4.! 10 
Table !4.1 11 
Table !4.1 12 
Table 14.! 13 
Table 14.1.14 
Table 14.1 15 
Table 14.1 16 
Table 14.l  17 
Table  14.1 18 
Table 14.1.19 
Table 14.1.20 
Table 14.1.21 
Table 14.1.22 
Table 14.1.23 
Table 14.1.24 
Table 14.1.25 
Section 14 Tables 
Overall Preface Tables. Figures and Listings 
Summary of Study Completion and Withdrawal 
Summary of Withdrawal ITT Population 
Summary of\Vithdra\\·ai PP  Population 
Summary ofV,/ithdrawai Safety Population 
Summary of Screen Failures Enrolled Population 
Stimmary of Subject Disposition - Safety Follow-up ITT Population 
Summary of Subject Disposition - Safety Follow-up PP Population 
Summary of Subject Disposition - Safety Follow-up Safety Population 
Summary of Subject Disposition - Long Term Follow-up· Month X ITT Population 
Summary of Subject Disposition - Long Term FoliO\\·-up Month X PP Population 
Summary of Subject Disposition - Long Term Follow-up· Month X Safety Population 
Summary of Protocol DeYiations [TT Population 
Summary ofDc:nography ITT Populat10n .............. 
Summary of Demography PP Populat10n 
Summary of Demography Safety Population 
Summary of Medical History ITT Population 
Summary of Medical 1-listory Safety Population 
Summary of Prior Medications-A ML ITT Population 
Summary of Concomitant ?vledications-AML ITT Population 
Summary of Prior Medications-non AML !TT Population 
Summary of Concomitant \.1edications-non AML lTT Population 
Summary of Study Drug bage Rate Induction Cycle lTT Population 
Summary of Stud - Dmg Usage Rate Induction Cycle MITT Population 
Summary of Study Drug Usage Rate Re-induction {7+3) Cycle Safety Population 
Summary of Study Drug Usage Rate Re-induction (5+2) Cycle ITT Population 
Summary of Study Drug Usage Rate Consolidation Cycle l Cycle !TT Population 
Summary of Study Drug Usage Rate Consolidation Cycle 2 Cycle ITT Population 
Summary of Study Drug l:sage Rate Induction Cycle PP Population 
Summary of Study Drug Usage Rate Re-induction (7+3) Cycle PP Population 
Summary of Study Drug Usage Rate Re~induction (5+2) Cycle PP Population 
Summary of Study Drug Usage Rate Consolidation Cycle l Cycle PP Population 
Summary of Study Drug Usage Rate Consolidation Cycle 1 Cycle PP Population 
 
 
10 
Ii 
IC 
"
12 
13 
14 
 
 
 
 
 
 
 
 
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Page 4 of 105 


Statistical Analysis Pian 
CNTX-CX-01-2015-AML-1 
Final 
 
 
 
 
Table 14.l.26 
Table 14.!.27 
Table 14.1.28 
Table 14.1.29 
Table 14.1.30 
Table 14.1.31 
Figure 14.2.l 
Figure 14.2.2 
Figure 14.2.3 
Figure 14.2.4 
Figure 14.2.5 
Figure 14.2.6 
Figure 14.2.7 
Figure 14.2.8 
Figure  14.2 9 
Figure 14.2 JO 
Figure 14.2.11 
Figure 14.2.12 
Figure 14.2.13 
Figure !4.2.14 
Table 14.2.1 
Table 14.2.2 
Table 14.2.3 
Table 14.2.4 
Table 14 2.5 
Table 14.2.6 
Table 14.2.7 
Tabie 14.2.8 
Table 14.2.9 
Table 14.2.10 
Table 142.11 
Table 14.2.12 
Table 1--1-2.13 
Table 14.2.14 
Table 14.2.15 
Table 14.2.16 
Table 14.2.17 
Tab!c 14.2.18 
Table 14.2.19 
 
Summary of Study Drug Usage Rate Induction Cyc!e Safety Population 
Summary of Study Drug Usage Rate Re-induction (7+3) Cycle Safety Population ................... 
Summary of Study Drug Usage Rate Re-induction (5+2) Cycle Safety Population. 
Summary of Study Drug Usage Rate Consolidation Cycle I Cycle Safety Population ................ 
Summary of Study Drug Usage Rate Consolidation Cycle 2 Cycle Safety Population 
Summary of Treatment E:-.:posure by Cycle Safety Population 
Overall Sun·iYal plot lTT Population 
O\erail Su01\al  plot \llrf Population 
..................... 
f 
O\crall Sur\ 1\al  plot PP Populatmn 
{i 
(  [F  plot for e\enl tree sutvl\al (from date of random1?..at1on)  lIISpf:'!flation 
C!F plot for event free surviYal (from date ofrandomization)\[[T Population 
CIF plot for leukemia free sun·iya] ITT Population 
CIF plot for leukemia free survival MlTT Populauon 
CIF plot for neutrophil (>500) reco\·ef)' (from date ofrnndomizationi ITT Popu!ation 
CIF plot for platelet (>20000) recovery (from date of randomization) ITT Population 
CIF plot for neunophil (> l 000) recovery (from date of randomization) ITT Population 
CJF plot for platelet(>100000) recovery (from dai,:;. of randomization) ITT Population 
CIF plot for relapse (morphologic CR) ITT Population 
CIF plot for relapse (composite CR) ITT Population 
CIF plot for relap:>e (composite CR) MITT Popular ion 
Primary Outcome-CR ITT Population 
Primary Outcome-CR M!TT Population ................. 
Primary Outcome-CR PP Population 
Secondary Outcome-CRi [TT Population 
Secondar:' Outcome-CRi MJTT Population 
Secondary Outcome-CRi PP Population 
Secondary Outcome-Composite CR ITT Population 
Secondary Outcome-Composite CR MJTT Population 
Secondary Outcome-Composite CR PP Population 
Mortality Day-30 iTT Population 
Mortality Day-60 ITT Population 
Mortality Day-90 !TT Population 
l\fortality Day-30 MITT Population 
!\fortality Day-60 MITT Population 
\fortality Da;,'-90 t\ffIT Population 
l\fortality Da:,·-30 PP Population 
Mor-..ality Day-60 PP Population 
Mortality Day-90 PP Population 
Summary of Overall Survival ITT Population 
 
30 
31 
31 
 
 
 
'E,) i/i,!t; 
 
 
 
 
 
 
 
 
Document Version: 20 i 8-03-08T07:32:05 
Page 5 of 105 
TT' 


Statistical Analysis Plan 
CNTX-CX-0i-2015-AML-l 
Final 
 
 
 
 
Table i4.2.20 
Table 14.2.21 
Table 14.2.22 
Table 14.2.23 
Table 14.2.24 
Table 14.2.25 
Table  14.2 26 
Table i4 2.27 
Table 14.2.28 
Table 14.2.29 
Table 14.2.30 
Table l-U.3l 
Table t-+.2.32 
Table 14.2.33 
Table 14.2.34 
Table 14.2.35 
Table 14.2.36 
Table 14.2.37 
Table 14.2.38 
Table 14 2.39 
Table 14.2.40 
Table 14.2.41 
Table 14.2.42 
Table 14.2.43 
Table 14.2.44 
Table 14.3.1.l 
Table 14.3.1.2 
Table 14.3. l.3 
Table 14.3.1...i 
Table 14.3. l .5 
Table 14.3.J.6 
Table 14.3.l.7 
Table !4.3.l.8 
Table 14.3.1.9 
Table !4.3.l.J0 
Table 14.3.1.11 
Table !4.3.l i2 
Table 14.3.1.13 
Table 14.3.l.!4 
 
Summary ofO\·eral! Survival MITT Population 
Summary of Overall Survival PP Population 
Summary ofOYerall Survival KM Estimate !TT Population 
Summary of Overall Survival KM Estimate MITT Population 
Summary ofO'"erall Sun:i\·al KM Estimate PP Population 
Time to EYent Free Survival - Days ITT Population 
Time to faent Free Survival - Days IVHTT Population 
Time to Leukemia Free Survival  -  Days {from  randomization) ITT  Population 
fime to Leukemia Free Survival - Days (from randomization) MITT Population 
Time to "Keutrophil Recovery (>500) ~ Days (from randomization) lTT Porulation 
Time to platelet Recovery· (>20000) - Days (from randomization) !TT Population 
Time to Neutrophil ReCO\"ery (> 1000) - Days (from randomization) lTT Population 
Time to plateiet Reco\·ery (>100000) - Days (from randomiz.ation) ITT Population 
Time to reiapse (duration of morphologic CR)- Days ITT Population 
Time to relapse {duration of composite CR) -  Days  fTT Population 
Time to E\·enl Free Survival - Days (from randomization) PP Population 
Time to Leukemia Free Sun:ival - Days PP Population 
Time to ;--.;eutrophii Recovery (>500)- Days (from randomization) PP Population 
Time to platelet R,,covery (>20000)- Days (from randomization) PP Population. 
Time to Neutrophil Recovery(>!000) - Days (from randomization) PP Population 
Time to platelet Recovery(> 100000) - Days (from randomization) PP Population 
Time to rdapse (duration of morphologic CR)- Days PP Population 
Time to relapse (duration of composite CR) - Days PP Population 
Subgroup Analysis-CR ITT Population . 
Subgroup Analysis-Composite CR ITT Population 
O\·erall Summary of Adverse Events Safety Population 
Summary of Treatment related Adverse faent ([darubicin) Safety Population 
Summary of Treatment related Adverse Event (Cytarabine) Safety Population 
Summary of Treatment related Adverse Event (CX01) Safety Population 
Summary of Adverse Event due to underlying disease or other drugs or chemicals Safety Population 
Overall Counts of Adverse Events Safety Population . 
Summary ofTEAEs by MedDRA System Organ Class and Preferred Tenn Safety Population 
Summary ofTEAEs by Preferred Tern, Safety Population. 
Summary ofNCl-CTCAE Grade 3 or higher TEAEs by MedDRA System Organ Class and Preferred Term Safety Population 
Summary ofNCJ-CTCAE Grade 2 or lower TEAEs by MedDR.i\ System Organ Class and Preferred Tenn Safety Population ................... 
Summary of Treatment-Related TEA Es by !'>,1edDRA System Organ Class and Preferred Tenn Safety Population 
Summary ofTEAEs by Relationship to Study Treatment by MedDRA System Grgan Class and Preferred Tenn Safety Population 
Summary ofTEAEs by Maximum NCI-CTCAE Severity. System Organ Class and Preferred Tenn Safety Population 
Summary of Treatment-Related TEAEs by Maximum NCl-CTCAE Severity, System Organ Class and Preferred Term Safety Popuiation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
46 
.46 
46 
46 
 
 
 
 
 
 
 
 
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Page 6 of 105 


Statistical Analysis Plan 
CNTX-CX-01-2015-AML-l 
Final 
 
 
 
 
Tabie 14.3.l 15 
Table  14.3  i !6 
Table  14.3 1  l 7 
Table 14.3. i.18 
Tabie 14.3.1  19 
Tab!e 14.3.1.20 
Table !4.3.l.21 
Table 14.3.2.1 
Table 14.3.2.2.1 
Table 14.3.2.2.2 
Table 14.3.2.2.3 
Tabk 14.3 2.2.4 
Table  14.3 2.2.5 
Table 14.3.2.2.6 
Table 14.3.2.2 7 
Table 14.3.2.2.8 
Table 14.3.2.2.9 
Table 14.3.2.2.l0 
Table 14.3.2.2.ll 
Table 14.3.2.2.12 
Table 14.3.2.2.13 
Table l4.3.2.2.!4 
Table 14.3.2.2.!5 
Table 14 3.2.2.16 
Figure 14 3.2.2.17 
Figure 14 3.2.2.18 
Figure 14.3.2.2.19 
Figure 14.3.2.2.20 
Figure 14.3.2.2.21 
Figure 14.3.2.2.22 
Table !4.3.3.1 
Table 14.3.3.2 
Listing 16.2.1 
Listing 16.2.2 
Listing 16.2.3 
Listing 16.2.4 
Listing 16.2.5 
Listing 16.2.6 
Listing 16.2.7 
 
Summary ofTEAEs Causing Discontinuation from Study Treatment by CTCAE and worst CTCAE grade Safety Population 
Summary ofTreatment-Related TEAEs Causing Discontinuation from Study Treatment by CTCAE and worst CTCi\E grade Safoly Population 
Summary ofTESAEs/Serious TEAEs by MedDRA System Organ Class and Pret"erred Term Safety Population 
Summar:• ofNCI-CTCAE Grade 3 or higher TESAEs/Serious TEAEs by MedDRA System Organ Class and Preferred Tenn Safety Population 
Summar;,- ot'NCI-CTCAE Grade 2 or lower TESAEs/Serious TEAEs by MedDRA System Organ Class and Preferred Tenn Safety Population 
Summary ol"Treatment-Related TESAE/Serious TE/I.Es by CTCAE and worst CTCAE grade Safety Population 
Summary ofTEAEs Leading to Death by MedDRA System Organ Class and Preferred Term Safet) Population 
Death Listing Safety Population 
Summar;,- of Laboratory Test Results and Change from Baseline by Visit-Bone MaITO\\- Safety Population 
Summary of Laboratory Test Results and Change from Baseline by Visit-Hematology \\·ith CBC Safety Population . 
Summary of Laboratory Test Results and Change from Baseline by Visit-Coagulation Safety Population 
Summary of Laboratory Test Results and Change from Baseline by Visit-Serum Chemistry Safety Popuiation 
Shifl: Tabie of Laboratory Test Results (counts) by NCJ_Cf'CAE grade· Hematology \\"ith CBC Safety Population 
Shirl Table of Laboratory Test Results (counts) by NCl_CTCAE grade: Coagulation Safety Population 
Shitl Table of Laboratory Test Results (counts) by NCJ_CTCAE grade: Scrum Chemistry Safety Population 
Shift Tab!e of Laboratory Test Results ( 'G) by NC!_CTCAE grade: Hematology with CBC Safr:t:s Population 
Shift Tabie of Laboratory Test Results(%) by NCJ_CTCAE grade: Coagulation Safety Population 
Shill Tabie of Laboratory Test Results('%) by NCI_CTCAE grade: Semm Chemistry Sater:- Population 
Shift Tabk: of Laboratory Results (coums) Hematology with CBC:Hemoglobin Safety Population . 
Shift Tabk or Laboratory Results (counts). Coagulation:Anti-Factor Xa Safety Population 
Shitl Tab!e of Laboratory  Results (counts):  Serum Chemistry:Albumin Safety Population 
Shiti. Tabk of Laboratory Results(%) Hematology \\"ith CBC:Hemoglobin Safety Population 
Shift Tabk of Laboratory Results(%) Coagulation:Anti-Factor Xa Safety Population 
Shift Table of Laboratory Results(%) Serum Chemistry:Albumin Safety Popu!ation 
PT/fNR over time Safety Population 
:\PTT m·er time Safety Population 
:\nli-factor Xa over time Safety Population 
fibrinogen O\·er time Safety Population 
D-dirner over time Safety Population 
Platdcl count over time Safety Population 
Summary of ECOG Status at Screening and Vital Signs at Screening and Start of Consolidation Cyc!e Safet) Population 
Shift of ECG Results Safety Population 
Subjects Screened 
Subject Disposition 
Suliiect Treatment Aliocation 
Protocol Deviations 
Inclusion Criteria 
Exclusion Criteria 
Study Population 
 
 
 
 
 
 
 
 
 
 
 
. 68 
68 
69 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
82 
83 
 
 
 
 
 
 
 
 
Document Version: 20 l 8-03-08T07:32:05 
Page 7 of I 05 


Statistical Analysis Plan 
CNTX-CX-01-2015-AML-1 
Final 
 
 
 
 
Listing  l 6.2.8 
Listing 16.2.9 
Listing 16.2.10 
Demographics and Baseline Characteristics 
Medical History 
Prior ;,viedication 
Listing l 6.2.1 l 
Listing 16.2.12 
Listing 16.2.13 
Listing 162.14 
Post kdication 
Study Drug Usage and Exposure 
Efficacy pan 1 
Listing 16.2. l 5 
Listing 16.2.!6 
Efficacy part 2 
Adverse E\"ents Safety Population 
Listing 16.2. l 7 
Listing 16.2.18 
Listing 16.2.19 
Listing 16.2.20 
Listing 16.2.21 
Listing 16.2.22 
Listing 16.2.23 
Listing 16.2.24 
Listing 16.1.25 
Listing 16.2.26 
Adn:rs<: E\"ents Causing Discontinuation from Study Treatment Safety Population 
Ad\'crse E\"ents Causing Interruption from Study Treatment Safety Population 
,\dvcrse E\·ents Causing Dose Reduction from Study Treatment Safety Population 
Treatm.:nt-Related Adwrse Events Causing Dose Reduction from Study Treatment Safety Population 
Serious Adverse hents Safety Population 
Laboratory Findings - Bone I'v1arro\\· Safety Population 
Laborator:,· Findings - Hematolog;, \\·ith CBC Safety Populatior. 
l,aboratory Findings - Coagulation Safety Population 
Laboratory findings - Serum Chemistry Part  l  Safety Population 
!.aboratory Findings - Scrum Chemistry Pa.rt 2 Safi':ty Population 
101 
Listing i 6.2.27 
PK listing Safety Population ............... 
102 
Listing 16.2.28 
Vital Signs Safety Population 
103 
Listing 16 2.29 
ECG Results Safety Population 
104 
Listing i 6 2 30 
Physical Examination Results Sater;, Population 
105 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Document Version: 20 i 8-03-08T07:32:05 
Page 8 of 105 


 
 
 
 
 
 
 
 
3. 
SECTION 14 TABLES 


 
 
 
 
 
 
 
 
Overall Preface 
Tables, Figures 2nd istings 
 
@ 
Patient :Sxcludeci from Safety ?o;:;:..:.12::ion 
s 
Patier.t  -
t.XC.'!_UC.E..0.   fro2,   Ir;c:er,::-to-  rea t   Populatio:1   (ITT) 
& 
Patient E:zcluded fro:n Per-Protoc:o.:.. Populatio,c 
 
{?.) 
Repeat: Visit 
 
{W) 
Patient ,:,Ji thdre,-; 
 
; :, 
Patient c1isra:1dornized 
 
c'i. . 
lot     Applicable 
 
NC 
Not      Calculated 
 
ND 
Net Do:-1.e 
 
NK 
Not K:r:own 
 
?<IR 
Not Recorde::i 
 
 
?rograE Nazne: 
Listing Source: 
Date Ge'1.e.::ateci.: 
Page x c,f 


 
 
 
 
 
 
 
?aDle  :;..4. 
Su,c;:;:ary   of    S::udy   Co:;r:pletie>r-,  and Withdra·dal 
 
Cont::-ol 
-o·•· rv-o, 
:-!igh CX-01 
Total 
 
Patients Screened 
xx;,: 
Patie,. s Rando::nized [a] 
XXX 
XXX 
XXX 
>:z:-: 
xx.x% 
?.andom zeC ar,d not tr,::oated 
[bj 
zxx 
xx.z%' 
:,;:--:x 
;-.:x. :,;:-'i., 
XXX 
>.A. >,l, 
; xx 
xz.:--9- 
Rar:do'"- zed ar:d -::.reateci lb} 
xxz 
xz. 
::-:zx 
X}:. Xi·, 
XXX 
xx.x'ic.) 
XXX 
x :.z::, 
ITT ?op'..<lat en [b 
XXX 
xx.x>,; 
XXX 
xx.x%:: 
:.;xx 
xx.x%) 
XXX 
xx. 
?er ?rotoco ?opulation. [bj 
x;-:x 
xx.x% 
XXX 
x:-: 
;-:xx 
xx, 
XXX 
xz.;-:i;) 
Safety Pcµu atio,, [b] 
XXX 
xx.x°:'' 
xzx 
xx.x ,• 
XXX 
xx.x0) 
xzx 
xx.x%) 
Completed  St:c,.d 
'.b] 
:G{X 
xx.:,J, 
;,;xx 
xx.x 
XX}: 
;,:x.xco) 
·,:xx 
xx.xS;\ 
Entered XXX Cy le Jl .c'is!..t [bJ 
XXX 
xx.x'i 
XXX 
xx.; 
xxx 
( xx.x%) 
XXX 
XX.X '' 
repeat :':or a::. visi::s fro2 Dl 
XXX 
xx.x':1 
xx;.-· 
:< 
:u:x 
i xx.xS) 
xxx 
( xx.x%) 
Primary ?eason fer Ea:-ly Disconti::.uation 
[c] 
Reasor. 
x:c-.: 
xx.x':c' 
XXX 
zx.xrs 
x:o: 
xx.x'o 
xx;,; 
xx. x'o) 
Reason 2 
:o:x 
xx.x 
zx:,; 
xx. 
XXX 
xx.x'i,; 
XXX 
xx. x'2) 
Reaso:i. 3 
xxz 
xx.x 
XXX 
xx.x%) 
XXX 
xx.;,:S 
xxx 
( xx.x%) 
etc 
XXX 
:,;:x.x 
x;.-;x 
:-:x.z'" · 
XXX 
xx.x% 
:-:xx 
xx.z'2) 
 
[a: The den0:r,ir,ator for percentage ca cu ation s !:lase::i er, r1:J.."1lber of patien".:.s sc::::eened. 
[b} The der:orr:.inc.tor f-'.}r percentage ca cu a::ion s based er:. n;_i,_-::ber of pat:ier:t:s ra::-::ciomized ir: each grcc:p. 
[c] The denominate::- for percentage ca cu a-:::ion s based c,, the nu."1\De:::: of pa-:::::.e,;ts ;...,ho did r.ot comp.Lete t:"::e study for each gro-c1p. 
P.t:09't6:minit1g·:Notes: 
'Obtain··reasons £,or :early· di'SC_onti nua:ti()n from. CRF. 
Progrc.m Ne.me: 
D2.te Ge::.e:::.-2te1: 
Listing Source: 
Page z 0£ y 


 
 
 
 
 
 
 
Table   2.'<c. .2.2   
Surnxo.ary of Wi tC'.dra·,.•al 
ITT ?opc1lation 
Co:n-::rol 
Low CX-Jl 
Eigr. cx-o::. 
 
Overal.:. 
 
 
 
Primary Reason fo.:c Ea.:c::.y Discoc:tinuatio" 
[aJ 
'.N 
XXX) 
C 
(N  ""   xxx) 
n (%; 
't = :,::xx} 
XXX) 
n ( ;) 
Reasor; 
Reason  2 
?-.easor:  3 
x;,:x 
XXX 
zxx 
x;.:, 
xx. x%'• 
xx.  x'1'', 
x:-:z 
XXX 
XXX 
X);. Z 
xx. 
xz.x 
xzx 
xxz 
XXX 
xx. x;,, 
xx. 
;,:z .. ,. 
XXX 
XXX 
xx;.: 
xx.x 
xx.x 
xx.x 
etc 
:-:xx 
x. x-"'- 
xzz 
xx.:-:"' 
XXX 
xx. 
:,:xx 
xx.x% 
 
 
[aJ 
::i.e   denominator   for    percer:tage   ca.'...culatic:-.  is    based   on  :nu.:sb,2r   of     patie:-.::s i:n the 
vr:,;;n1.'.a-::io:-, set ·,rithin each group. 
Pi:o'g_i- ing:·Notes: 
_Obtain·.reason·s foi -.earl:,/ _discontinua_tiO:ri· fi-o:m CRF. 
Program Name: 
Listing SoJrce: 
?,epeat for the fol-2.owir,g displa :s: 
Date  Generated: 
Page x of y 
Table :':.4. l. 2. 3 Su.Tu"tlary of Wi thdra·,.-a::. PP Population 
.;dd: 
Footnote:   la; 
"e denominator for :=,ercer,tage calculc.-:::io:-i is based on ;,;;.sber of patierats 
 
Delete: 
 
 
t:'le ?? ?opulation set , ithin each groc:p. 
Footnote: La; The denomir.ator for per:::e::tage calculation is based on n:...:...'Tber of patie,;ts · ::: ,e :::-: Population se::: 1,,,ithi::1 each group. 
 
Table 14. l. 2. 4  SUJ.-:-.mary  of \•Ii thdra'.12.l  Safet'::/  Population 
Add: 
Footnote: [aJ The deno;r,inator for percen.-;:age calculatioD is based or. nu.--r.ber of pa.tier.ts .:.:-, :::;-::e Safety Populatior:: set ,...,·it:J.ir. each grou?, 
 
Delete: 
Footnote: [aJ The denominator for percentage calcu::.ati.on is based on nu.'T<Der cf pac::ier,ts in ::he 
 
 
Population se:: within each gro;ip. 


 
 
 
 
 
 
 
Table 14.1.2.5 
S·u..,--r:TI',ary   o::  Screen Fai2-11::::es 
:='.n,olled  Population 
 
rota.!.- 
 
Patients  Sc:reened 
xx;-; 
 
?atier,ts Rancio:2.:i.2ed [a] 
 
Patients Screened bu;:: not Randccnized [a; 
 
XXX 
 
xx:-: 
 
xz . :,0:0 ) 
 
xx.z½ 
Screen 
a :.:re :reasor. 
Sc.::::een a :1re reason 
Screen a  ;;.re  reason 
etc 
LbJ 
, ; 
LOJ 
xzx 
xx;-:: 
xx;-: 
Y:•:.z'i:) 
z:,:.x', 
:,:,:. xS,, 
 
 
 
No   e:    If    a    pc.   ient  has rrrc.ltiple   sc.::::een   ::  ilu::::e    easor,s,    t'.ne   patient   is   cou:--,ced   under   each   screer:  faiL:re   reascr:. 
la The deno;n nator for perce:1tage calcv. a;::2.or-: s baseci or, nurrcbe!."" of patie:its enrolled. 
[b Theder,om nator for percentage calc'..t at.ion s Daseci on the number of patients who got screened bL<:: r.ot rar,cio:.r.iz.eC. 
?rogram c'lame: 
Listing Source: 
Date Gene::::ated: 
age 
of 


 
 
 
 
 
 
 
Tc.ble   ,::.  .c.2.6 
:::;urr,rrtary  of    Subject  Disposition.  -  Safe":y  ?ollow-up 
:::,:-  Popula"'.:ion 
 
Dispositicr:: 
:or;.trol 
(lS co x;,::,:) 
 
Low CZ-Ol 
( J  = z:-:z\ 
( i hx 
Gl 
 
Q;rerall 
(N xxx) 
r, 
(O;) 
n (%) 
 
 
 
Safety .:cllc;-.,-,..1p 
Dici not ccrt,plete 
0 rimc.r y ?.eason 
perf,-:,r:;rced 
safe 
fcllo -,-up 
[aJ 
XXX 
XXX 
xx.x'o) 
X '..X''.') 
XXX 
XXX 
xx.x;/ 
;-:x.x" i 
;-: 
XXX 
:-:X.X'c 
x:-:.x<:c·, 
XXX 
xzx 
xx.x i ·, 
xx.x%'. 
Rease:,. 
x;.:x ( ::o:.x't) 
XXX 
;-::-:.·,•'i•' 
XXX 
xx.x':i 
XXX 
zx.x%) 
Reason 
XXX 
xx. x'Sl 
XXX 
XXX 
( X•:.;-:½' 
x::--:x 
xx.xf,) 
?.eascn. 
x:·c-: 
xz. 
x:o: 
XXX 
;-:x.x'.;·, 
xx;,: 
xx.z%) 
XXX 
xx. z%) 
x;,:x 
xzx 
x:-:.x 
XXX 
xx.z%) 
Other 
:-:xx 
ZZ.X'O 
XXX 
xz. xr-,·; 
XXX 
xx.::--; 
XXX 
xx.x':,,' 
Ongoing ;-:i th 
safety follow-up 
x:o: 
x•:.xG) 
: xx 
zz. 
XXX 
:-:x.x 
XXX 
xx.x%) 
 
The deno.r,i;:atol:'  for   perce::-ltages  ::.s  the    nwcher  cf   patien.ts .::.r: the 
IT';:' Pcp,.:laticr, for each Trec.t:ser:t group. 
For  [aJ,  U·.e   Cenominator  for  percentage  calcc.:lation  is  based  0:1  the     r-,u..,--;.ber   of     patients ·,,ho   Cici   not    complete  safety  follc·,.; '--'P  for 
each group. 
Prcgra C1a,ne: 
L st--i--,g SO"'""C""" 
Repeat fer the fcllow:cng dis:::,lays: 
:}ate  Gene::::ateci: 
Page x of 
TabJ.e 10..:.2. 7 Sllic.:7:lary of S\;bject Disposition - Sa'.:ec:y Follow-up ?P  ?c:;:;c1latio:1 
Add: 
Fooc::-iote: The deno:mi:1ator fer perce:1tages is the Cl..hc'..ber cf patier,ts i:1 ::he PP Populat::.on for eac:'. TreatE,ent group. 
Delete: 
?ootnote:   ?he  der:omi:cator   .:or  percen:::ages   is   t'."'.e   n.uillber   of   patier-.ts in  ::he 
Pop'..:la::ior: for each Treat:;rrent grou.p. 
 
Table 
l . .e:.8 Su.rr.ncary of Sc.:bject Jis;,ositio;-i - Sa::"ety Follo,,'-up Safety Population 
.Sdd: 
Foo::rwte: '?he deno:;r;i:iator ::er percem:.ai;es is the m.;_,_;1ber of patier,ts ,.., the Safec:y ?cp;..;2.ation for each Treatr:",ent gro,.:p. 
Delete: 
::'00-::10-ce: ':'he denomiriatcr for perce:-ic:ages is the r:urnber of patients " c::he :TT Pop1.,;.2.ation for eech Treat:nent i;roup. 


For 
1 
 
 
 
 
 
 
 
:'able 14.l.2.9 
S T01a:ry of Subject Dispositior:: - Long  Te:cr:1 FolJ..o •:-·crp:  !':onth X 
--""'7   Pop--1latior, 
Ji s::--o"' "'"°'<'"' 
::c:,t:rol 
:.o'-'.' CX-0.l 
= XXX) 
(N = XZ:i(i 
,, !% ) 
 
High c:.,:-c::. 
(K = XXX) 
n 
 
o·,,rerall 
('.') 
xxx} 
 
 
 
Patients with long te:rrr, fol::.ow-t.:p La) 
::,ong ter:n follow-up stac.t.:s '.DJ 
xzx 
xx.xS) 
XXX 
xz.x%) 
:-:;-:x '. 
xxz 
.--.- .)-:':' 
Death 
X ::< 
:-:x.xS) 
x;-:;-;: 
xx.x 
xxz 
_;.:;-;_;.:;) 
XXX 
zx.x'i 
Ali·,se 
xx.x%) 
xx;-: 
xx.x 
x:-.;:x 
.:-:x.x\' 
:o:x 
xz.x';;c 
Recu:::-rer::ce 
:-::-;:;,: 
x:-::.x":) 
;.c-.;:x 
x; .x 
XXX 
Y.X.Z-, 
XXX 
xx. x'::' 
;--:;-:y 
zx.x'c) 
XXX 
x:,:. x%) 
XXX 
xx.z -) 
XXX 
X:O<. X',; 
For ;:atients ;,;ho died_. p:::-irr,ary ca.use of 
dea-.::h [c] 
Res.so:: 
XXX 
xx.x 
x;-.;:x 
xz.x 
xxz 
:,:x.z'C 
xxz 
x;,-:. zs 
Reason 2 
XT" 
x;-:. :(%) 
xx:,: 
xx.zC 
XXX 
xx.;-;SC 
z;-:x 
;,-;x. :;o) 
:,:zx 
xx.x%) 
XXX 
xx.x% 
XXX 
x:,· .Z''., 
XXX 
xx.x•t' 
 
 
Foe'.'   a 
the 
de;:,.o:m nator o::: pe:::-centages is t:'.e ,, "".'<Der cf patie::1.ts in the ITT Populatior. for ea..ch Treat:r,er,t group. 
E'er     b 
".:he   denom   nator      or   percentage   c2lculatior,   is   :Jased   on   r;,.;.rr.ber   of     people   wi::h   recorded   long   term   fol  lo·..-   up 
status. 
E"er 
c 
::he deno:m nator or percentage calcu:ation is based on the rn.uc.ber of patients ,·:10 died. 
;c. o,...,..;.,n N:,-z.,::: 
::,ist::.r.g Source: 
Repeat for the follow.ng disc:a,s: 
D".,..""" s'°''"'e at"""'" 
Page z of 
Table "L l.2.10 
Add: 
Su.mrr.ary o::  Subject Disposi_tio'1 - "-'0:1.g  "Ier:rr: Follow-up: l:ionth X  ?P Populatio;; 
r - """'' 
Delete: 
the denorr.inac:or fo:::- percer.tages is the :.c:.cc.ber cf patients in the ?P Population for each TreatG.ent group. 
:'or  [a],  the cieT10:minac:o:::-   fo:r  percentages  is   the  ,, "7.ber   cf    patier,ts •  '"l the 
Populatior. for eac:1 Treatment grc;.:p. 


 
 
 
 
 
 
Table 14.. 2. 
F-.dd: 
 
ScL--:-:mary of Subject Disposition - Lo;-:; Term Follow-up: Moc:th x Safety Populac:ion 
For   [aJ,  the  derwc:-,inator  for   percer:.tages   is   the  :1;-1,_--:-ber   o-:     patier,ts .:..r,  the 
Safety ?cpulation for each Treatmer,t g::::-o'..:.p. 
Delete: 
For [a), t:t:e denomina.tor for percentc:ges is t:1.e nurrber o:'. pat2-e:1ts in the .ITT ?opulat:i.or, for each ':'reat:ne::t g::::-oup. 


 
 
 
 
 
 
 
Table l4.l.2.l2 
Swill--rsary of Protocol De-v-.:.ations 
ITT Populatior, 
?rotocol Deviatio:c 
:ontrol 
(N = XXX) 
n (%) 
 
Low CX-01 
(N = XXX} 
n (%) 
 
High CX-01 
{N = xxx) 
n {%} 
 
Overall 
(N  = xxx) 
n  (%) 
 
 
 
At Least l Major !?:rct :col Dev.:.at.:.0:1 
xxx ( xx.x:;) 
XXX 
xx.:-:%\ 
xx.z%'. 
;:xx 
x%) 
1-:ajor ?r.-otocol De,,iat.-_0:1 l 
XXX 
xx.x%) 
XXX 
x: .:-:t l 
;{;,;:{ 
zx.x% 
xzz 
_,,,;;:. i.·o ': 
etc 
 
 
 
 
 
?rosr-am Name: 
Listing Sou:rce: 
Date Ge:1erate-'.:i: 
Page x of 


 
 
 
 
 
 
 
Table 14.:.6 
Su.i"-<-r.ary   of    Demograph:.,· 
,,,...,.  ?opu.lati.on 
 
 
 
Age Categories 
 
 
 
ea.rs n (%) 
 
:or,trol 
(N = xxx) 
 
Lo;-: CX-01 
= xxx.: 
!'. ( % ) 
 
Eigh CX-01 
{N = ZXX) 
n 
 
07erc.ll 
 
N 
:-:xz 
XXX 
XXX 
X>-:X 
<Category 
e.g. < 70> 
·-::-:;-: 
:,;x. 
xxz 
XX.X'O 
XXX 
xx.x 
xx:•· 
xx.x 
<Cc.tegory 2, e.g. :C: 7C> 
XXX 
xx. 
;,:xx 
xx.xi} 
·-:;-:x 
xx.x 
:-:x 
·,:x.x 
etc.. 
:o::--: 
xz.zf,'• 
XXX 
x%) 
zxz 
xx. 
zx.x 
";ge ;yea.rs) 
n 
>-:xx 
xzx 
x;-;:x 
XXX 
w.ec.n :_s.6. 
xx.x 
xx. xz' 
zx.x 
xx. xx) 
.xx 
xx.xx) 
:n:.;,;x ( :--:x 
medi.C<c: 
;c-;:.x 
xx.:-: 
zx.z 
; :;,:. xz 
rEin 
xx.x 
:--:x. X 
.x 
z 
:cc.:-: 
:--:x 
xx. 
:-sx.x 
X}:.;-;:x 
Ger,der n 
t; 
:o:zx 
XXX 
;-:Z)'. 
x:,,-- 
112le 
:-:xx 
X. X'5 
;-:xx 
xx.x½) 
XXX 
x: . x ) 
;-:;-:x 
zx. zf,) 
Ferne.le 
x:-:x 
xx.:,: 
;,:xx 
x x . x 0o\ 
xzx 
xx.x'i:) 
XXX 
;,:x. ·Sc' 
 
:.:rote: De::,o::n.inators for percentages are based or, t:'le m:u--:-J.:;er of pat.::_ents ;,·ith r,on-ITcissing dac:a in ec.cr. ?reatme;o,t g::m.ip £or t:'.e relevant -,,a:::iable. 
[a] Age is ca:culated as calendar years £:.::om. birth to ir:!forrr-_ed consent 
 
Program :-lame: 
Listing Source: 
 
Date Ge::1erate8.: 
?age x o;'. 


 
 
 
 
 
 
'l'a:Cle 14.1.6 
S1J_._TfJ,ar:; :J,._ u,:;?, g,._o.1:-':,y 
IT? Populat:.on 
 
:ontrol 
(N = xxx) 
 
Lo>·i CX-Gl 
(N = XXX) 
High cx-n:: 
:::: = :o:x) 
 
Q,;erc.::..l 
()i 
XXXi 
BMI (kg/m:) 
n 
meac \S .d. ·, 
,.,,,,,d 2" 
 
rr,ax 
Race Categories 
:1 i ") 
 
 
 
 
 
 
 
 
 
:.:xx 
n 
 
 
 
 
 
 
 
XXX 
'- 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxz 
'I"·'c· / 
 
 
 
 
 
 
 
 
;.;,o: 
 
 
ec:c.. 
<Cac:eg-ory    ,    e.g. Asias> 
<Categcry  2,  e.g. Slack> 
XXX 
;c-;x 
;c-.:x 
xx.x% 
xx.x% 
xx.x':: 
:o:x 
;-:xx 
XXX 
xx.:- 
xx.x\'· 
:.:x.x'o 
>:xx 
:•:x>: 
XXX 
xx.x ) 
xx.z l 
X1/.X%) 
:-:xx 
XXX 
:o:x 
xx.x 
xx.x 
xx.x 
Ethnicity r, 
 
 
 
Ar L n 
 
 
zx.:,:%) 
xx.z%) 
xx.:-:%) 
 
<de no·v·o>  
i<XX 
xx.x%) 
XXX 
xx.z>·' 
x:-:z 
;-:x. x½) 
;,:::,::z 
xx.x%) 
<secor.dary> 
:-;xx 
xx. 
x:o: 
xx.zS·' 
x:n: 
xx.x%:- 
XXX 
xx x%) 
 
I cte:   Denc:ninators   fo::::  percentages   are  Cased   on  the   nUJ-:-ibeY   of     patie:--.ts   idtl1  nor.-rr,issir.g  data   ir:   eacr.  T::::eatment   gro-u.p   fc::::   the     ::::e  l  e  0: a"   t    va::::iable. 
a: Age is ca.':.c.:lated as calendar ;_:ears frow. birth to .:nformed cor:sen-r 
 
Program Name: 
Listing SouYce: 
 
Date Generat.eci: 
Page z of 
XXX 
:·:xx 
xx:;: 
::--:xx 
x;.:.:.: 
xx.xx) 
xx.x 
xx. ;.:.x) 
X{. XX 
xx.xx: 
xx.xx ( xx.xx) 
xx.x 
xx. 
xx. 
.?::< .zx 
xx.x 
xx.x 
xx.z 
xx.xx 
xx.x 
xx. 
xx.x 
zx.x;-: 
N 
<:,Jot 2ispc.:::ic or L2tino> 
xzx 
:.:xz 
XX.X'S 
x:-cx 
XXX 
XXX 
xx.;,:%/ 
x:-:x 
:c,.:-c1•, 
;,::-o: 
:c-:z 
<Eispa ic or Latino> 
XXX 
xx.x%'. 
XXX 
xx.;.:'; 
;.;;-;:,: 
xx.x':;) 
:-.:xz: 
etc .. 
;,:xx 
xx %:< 
XXX 
xx 
xx:,: 
xx. z2,', 
XXX 
(%) 
·o,x 
xxz 
xxz 


t;
:<
" 
" 
,, 
"
aj
r: 1:: 
'"
"
m ·o 
j.J
 
 
 
 
 
 
 
 
 
, 
>, 
0 
-1 
-, 
0 
 
 
 
X 
X 
 
 
,--I X -· 
,--1 X 
1\1 :-: ' 
H 
qJ II 1: 
:o-: 
 
 
 
.-. 
C) 
:
>,.;
; :X,:; :,s,;: 
 
 
 
 
 
>: 
:,:; >: 
X 
 
 
:,:;   X    :,.  ;,:; 
X   ;,;   X  X 
 
 
 
 
:"i 
 
 
,;:,: 
"' 
- 
Xu' 
,[: 
X _,. 
 
X 
X X :-.: X 
 
X 
X X X : . 
b> II 
.,.f 
r:: 
:i:: ,.:: 
:--;   :,;  :,;  :,; :,; 
X   :,:;   X    X   X 
:-.: 
X   X   :<  :,;  X 
X   Z<    X   ;,;  >; 
:,: 
 
 
 
 
 
,-·I 
0 - 
I   I'; 
,:    X   -. 
(.)     :,:;  o'P 
 
o
f.     II    r: 
,-1 ,?; 
 
 
 
 
 
 
 
 
 
: 
,--1   :,; ,. .. 
0     X  <'" 
 
'X ·;:; 
X     :,;  X 
X   >  X 
 
X    X    X  X 
:,;   X   i';  ;,; 
X   :-:   X  X 
 
 
 
 
 
 
:,; 
:,: 
:< >C: >C: 
 
 
 
 
 
X X X :< 
Q
X    X:,;
Xxx
:,; x
X 
 
X 
X 
 
 
 
 
X  X   :,; 
X X :< X >: 
i X X :-C.: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
<J 
"' 
"' 
"0 ' 
"' 
,",,' 
""' 
1"n
-'   II    c: 
0 ?.', 
' 
:,; :,:; 
>: 
X     :-.: 
:,; 
: 
 
 
 
 
 
 
,'a° 
aj 
 
 
 
·",-f' 
Y) " 
OJ    < 
t11 <IJ 
<IJ Tl 
J.J 
OJ 
Qu
J  ,--1 
<  u 
"0,'  (() 
"o   'd'" 
"""' 
"nu' '" 
 
 
'O 
 
r.! 
 
aj 
·d 
'O 
d 
 
 
'O 
 
r.: 
-•       QI 
(/) ,o 
-,  ,-1 
0     "j 
,Io,! ,-u-; 
!C   <\1 
 
.. "u' 
F.i 
0" 
 
 
()1 
1.:  -',-"f 
1.:  .,"-1' 
i
,oll"
'O' 
 
 
.,-1 U 
!ci 
lli  J 
I\J   () 
<1--1 
,; 
, 8 0 ,-, ("•1 
r: m fil 
0f;!   ·d"' 
C") '  QJ 
:Z, {j) 
8 tn 
"(J,' 
,.:: 
.•   a"; ' 
,o r.-1 
)-E  ·,·I 
(_ 
t)> 
0 
.,-j 
u 
QJ 
f,.J 
: 
w 
j) ,. 
0     (\j 
:C.::', ,_, 
tJ•.P 
0    o 
>1  ·,-1 
iJ,   ,-1 
8 8 
"
0 
"


 
 
 
 
 
 
Table 14.1.6 
s cr,ar-:,i  o::  De:r,ography 
.-  "0ru;a,-., ,, 
 
 
 
 
Tirr,e s::..nce Al·'!L dia-:;nosis n If:;\ 
 
:or:-::.:rol 
(N "' xxx; 
n ( % i 
 
KXX 
 
ow cx-e:: 
(fl "' xxx) 
::"l ( 'i;: 
 
zxx 
 
High CX-Ol 
(N "' XXX) 
r, ( % ) 
 
XXX 
 
o·,·e:rall 
XXX) 
n  {%) 
 
xxz 
<less o::.· equa.l to 60 days> 
<gre2.-::.er than 60 days> 
Baseline peripheral D:ood blast ao e 
:{XX 
;.:xx 
xz.x%' 
;en: 
X};. /;}' 
XZ.}:".i 
xx.x'2' 
XXX 
zxx 
ZX. X ) 
xx.x%l 
xx:.,: 
:•:zx 
XX.?:%) 
x;,:. 
 
 
 
 
 
 
:T,l n 
:r:ax 
Baseline ;:i 
r, 
::r:ear. is " 
:nedia:1 
rr:::..n 
rnax 
 
xx.x 
xx.x 
 
XXX 
xx.x ( xx. 
xx.x 
X:{.X 
xx.x 
 
 
:<'.x. 
xx.x 
 
XXJ: 
xx.z 
X{.X 
;,::,:.x 
xx.;,: 
 
 
 
 
 
:-:x:: 
 
xx.z 
)OS. 
 
 
XXX 
zx.xx 
;-::x.x 
xx.x 
J:X. X 
 
 
 
 
 
xx.xx) 
 
 
XJ: 
xx.xx 
 
xx;,; 
z;,:.x;,: 
xx.xx 
x;,:.xx 
xx.xx 
 
 
 
 
 
xx.xx) 
 
 
Note:   Deno i::ators   £0:::   percentages   are  based  on  the   r:.ucc:be:::  cf     patieuts  with  no:1-rr,issing data  ' 
each 'Ireat:ciec,t group for  ::he  relevant:  vari2D2.e. 
[a) Age is calc;;.la-::.ed as caler:dar year:s f.::-c,rr bi:cth to info:c-rr;ed consen.-::. 
 
Prograr:t ?-iar;,.e: 
=-.istir:.g Source: 
Repeat for '::.l e foJ.los-, ng displays: 
 
Date  Generated: 
Page 
of y 
['7 
XXX 
xxz 
XXX 
XXX 
'£es 
XXX 
xx.xs·, 
xzx 
zx.>-:'i·' 
xzz: 
zx.x? 1 
;-:xz: ( xx.x9;) 
No 
XXX 
xx.x':'s'- 
XXX 
xx.;,::::; 
xx;{ 
xx.x%'.· 
xxx 
xx.x'6) 
Baseline blasts i2.. D-::::--ce marrD",.' 
:,:xx 
xzz 
xx:•: 
XXX 
w.ean ;s.d. 
xx.x ( xx.z:--' 
xx.x ( z•:.xx; 
xx.xx 
xx.xx) 
xx. xx ( xx. x;,:) 
:necii2:-:: 
xx.x 
z;c 
xx.x 
XY.XX 


.•
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C 
0 
," 
•··I 
'j 
 
0 
 
 
u• 
w• 
 
 
., 
D 
 
 
m 


 
 
 
 
 
 
 
Table  14. 9 
s,.;;.c..,.c\ary of 1,Je:iical History 
IT'I ?opulation 
 
:ontrol 
(N.= XXX) 
n (%) 
 
Low CX-01 
(N = xxx:) 
n {%) 
 
High CX-01 
(N = xxx) 
n (%) 
 
Overall 
(N = xxx) 
n (%) 
 
Patie:-.ts 
Any Med.'"cal histo.:::y? 
No 
XXX 
:s:;,:. x'C; i 
XXX 
.:-:x. 
XXX 
xx.x'i 
XXX 
;,;;,:. 
Yes 
XXX 
:--;.x.x%) 
XXX 
:,,:x.x 
XXX 
;,:x.x<'' 
XXX 
xx.z% 
Medical E:'..story 
s:;,,-sterr, C-rgar: Class l 
XXX 
z·,, 
XXX 
xx.;,:;,; 
;,:xx 
xx.x'c,,) 
XXX 
x:,;:. Y ' 
?r2fA '"Pci. Term l 
XXX 
:,:z.x%) 
XXX 
xx. xi) 
>:xx 
xx.x -. 
xxx 
{ xx.x':C) 
c;;-:-,=,ferred Term 
xzx 
xx.x%} 
xxz 
xx. x ) 
XXX 
xx.x 
XXX 
xx.z'o 
?referred Term 3 
XXX 
.x% 
xx;,: 
x;,; 
XXX 
XX.X'J 
XXX 
XX.X'o• 
Preferred Term 4 
x:-::x 
XX>: 
xx. x ) 
XXX 
X}:. x;;} 
XXX 
zx. >> 
Syste;:,, Orgar-, Class l 
xzx 
XX.X'i;, 
XXX 
X?'.. 
XXX 
xx.x 
XXX 
xx. 
?re:'.erred Term l 
x:o: 
;--;_;--;_. 
XXX 
x;,:. -,-'.•. 
XXX 
xx.;,: 
x:-:::x 
xx.x2·, 
?referred Term 2 
XXX 
zx.zS) 
XXX 
xx.x't' 
;--;_xx 
xx.x 
XXX 
xx.x"c; 
Prefer::ed Terrr, 
XXX 
ZX.Z': 
XXX 
xx.x"s) 
XXX 
xz.zfj) 
xx:-: 
z:-::: 
?referred Term 4 
XXX 
xx.z'i;' 
XXX 
xx. c) 
x:o: 
zx_z,, 
XXX 
x .x'c 
 
 
The der,orr,icator for percentages is ".:he  m.:rrber  of patients i::i  the ITT  l?opc.:,la-::ion  for each T.:::eatrr,ent g!'."ol.:p 
 
Note: This table co:1t2ir:s CO'-.'.n:::s of patients. 
 
a pac:.ien-: had rt.ere than o:-:e r::edical history '.-,i t;'lin a preferred tenr:., ::he patient is coLln-:.:eci only 
orcce ,-:ithin 2 prefeYred  terE.  If  a  patient  had rr,ore  -;:t'.an   one  ::r;edical  '."',istor:,:  within  a  system  orga:1  class,  the patient  is  cc1..::1ted   once  for  
each prefer:::ed ter:n aGd 0:-1.ce fo::'.'  ,::he  sys-::em  organ class. 
Note:  '.edD?A Version 
used for coding. 
 
ProgracTL Ja'"-e: 
Listing Source: 
Repeat :'.:or the '::ollow:'..ng displays: 
 
::::ate Ger,e.:::-a.ted: 
?age x of Y 


 
 
 
 
 
 
Table 14. l. lO Su.7.rr:.ar· of 1,;edical History Safety Popc1lation 
Delete: 
Footnote: The de:ior:i.ir,at:cr for percentages is the nurrber of patier.c:s ,,, the IT·: ?cpulatic,"' fer each ?reatffi•'"r:t group 
 
Footnote:  r::cte:  T :is  c:ab2.e  co:1tains  co·o.nts  of  patients.  :;:fa  patier:::  had :nore  ::han  or.s-  rr,edical  :--listory  ·,;ithin  a  preferred  term,   the  patient 
is cccm1.:e::i. only cr:ce ·.-:ithin. a p:referred te::::m. :::  a  patient  had more  thar:.  one  med.ica1  his::or/  withia  a  sysc:er:-,  o::::gan  class,  the patier.t  is  cc:.:.nteci 
once ::':or each prefe:rred c:e::n: an-::":. on.ce  for the syste.cc, organ class. 
;iote: i:-1:eO:J?..n.  Version 
'..i.sed £0:::: coOir:g. 


 
 
 
 
 
 
 
Table  14.  l. 2.1 
s,.1,.Tu ,ary of Prior l'-'.eciications-f.'.!'-E, 
ITT Population 
WHO ATC Level 2 (Therapeutic Cl2ss} 
Generic Tenn ([a;) 
 
 
Patients with prio:::: ;,,2dicatior,- 
 
::::cntrcl 
(N = XXX} 
n (%) 
 
Lew CX-01 
(N = XXX) 
n {%) 
 
High CX-01 
{N = XXX} 
n    (%) 
 
Overall 
{N = xxx) 
n (%) 
_c1.1--JI.. 
:<:-:x 
>:x. :,;:% ·, 
xzz 
xx.x%} 
 
XXX 
.-·,:. x-"., 
xx; 
·.;;,:, .. 
 
A'!C :Level 2 T rm 
Ger,eric Med cation 
Ger,eric 1•1ed  cat 
on 
Ger ..e:::: i c Med ca-;:_ 0:1 
Ger,eric  Med  cat   on 
 
ATC :.,ev-el 2 T rm 2 
Ger,ec:ic Med catio,;_ 
Ge,,e::::ic Med cat on 2 
Gene.::ic Med cat 0:1 
Gene.::ic Med cat on 
 
;,;:xz 
:,;:xx 
z 
XXX 
·-:xx 
 
 
 
xxz 
XXX 
XXX 
 
x;,;:_xs:- 
XX.X·?,, 
;-:x.x%) 
;,:x.;,: 
 
 
xx.xi 
zx.x·} 
xx.x% 
xx. 
xx.z%) 
 
xzz 
x;{;,; 
 
 
;,;xx 
xzx 
 
xxz 
zx·,• 
XXX 
xxz 
XXX 
 
xx.z't,) 
xx.x S) 
xx.xi 
';:) 
x;,:. x%) 
zx.x' 
 
zx.x'o) 
xx.x%j 
xx.x%) 
xx.x% 
xx.x"o) 
 
xx;-.: 
XXX 
XXX 
XXX 
XXX 
 
zxx 
zxx 
zxx 
( 
XXX 
XXX 
 
:,-:x. xS" \ 
zx. ;.:% 
xx.z 
zx. ;,-i•' 
zx. ;,;?,', 
 
xx. z'.-' 
zx.  xS) 
 
xx.  z"·' 
x:•:. 
 
 
XXX 
XXX 
:x:>:" 
xx;,: 
 
XXX 
XXX 
:on: 
XXX 
XXX 
 
x:z. x·c 
X;{. X
03 
xx.x½ 
xx. 
xx.x% 
 
X>" 
xx.x'i-' 
xx.xc•· 
;,:
Z:
..
Xx
'.',
. 
 
 
 
The de:wminator for ::> rcentages is the nu.'7ber of patients in t:';.e :::·T Po;:,ulation for each Treatrr,ent g.::oup. 
Note:   P:;::ior  sedicatio;,,s  are  defined  as  Eedications  take:1 w.:.t:h  a   sta::::t  and  s-::.op   date  prier :::o  the 
first dayof stc:dy Treat:rr,ent. 
 
i,;ote:   P..  patient   Eay have   :.aken  :rcore   thar::  or.e  ::ceCication.   Therefore,    '.:he   SUiL',   of    nedicatio;-,   counts   ar..d    pe::::cent.ages  :na::,,  ;-,c-;:   equal   tl:',e   total   counts. 
:f  a  patient  had :r,ore  than  one :meciicaticr:  in  a  c2tegor-y,   the   patient  is   cour'.!teC  or'.!ce   ir.   that  cates,ory. 
'.a] ';.J.EC J::::c:g Dictiona::::y (Ver-sior. xx) was used for coding. 
Program,,1ing_ :NotEis-: 
Note  that ':thfr   first  row'will  chan,;;e   depen_d_ing  o_ri_ ·tn-e_··ti  t_lE_-'.   If-   the    ti"t_I_-_i _.:l_s'-..:pr_- -or_- medi6at:ion:...A.1-1L,  -then   it    i.s ·tp :_ c0;mpute  _any--priot:  1.'.ML 
medicat-i◊-ris;- If- the title -is concomitant -medi(;ation-At-1L then- the req:u_ired out-put is to compute any- A.ML conccn-sitant :m.edication, 
Program Kame: 
l;isting Source: 
epeat for the followir.g displays: 
Date   Generated: 
Pcge x of 


 
 
 
 
 
 
Table- L1. l. ::.3 Su.,.·:;r:iary of 2::::ior Medicaticr:s-:ior:. A.ML ITT ?opulatic,, 


 
 
 
 
 
 
 
?able 14.l._:_:c: 
Sur.cr.arv  of   Cor.cor:--,i tant   edica ticns-AML> 
I::'T  Populatior 
 
WHO - -IC Level 2 ,:Ther<l_ )et:tic Class: 
Ger,eric Te , ([a}' 
 
::ontrol 
(N = XXX) 
n {%) 
 
Low CX-01 
{N = xxx) 
n (%) 
 
High CX-01 
(N=x=c) 
n (%) 
 
Overall 
(N=xxx) 
n (%) 
 
 
 
 
Generic Med.icat on 
Generic Medioat 
0:-, 
Generic c1eCicat on 
Generic Medicat o;;. 
 
XXX 
xx.z%} 
XXX 
xx.x%:, 
:-::-:x    (  xx.x%\ 
XXX    (  XX.}:'z\ 
 
( 
x:-:x 
xx. x'.,) 
XXX 
(    xx.x0i 
x:-:x   (  xx.x% 
zx.x'!c 
 
 
 
xzx 
x:--:;, 
 
.z(, 
xx.x - 
:,x. x 
xx. 
 
 
;-:xx 
?:zx 
 
xz:--: 
 
·-··,·.  >:':,) 
xx.xi' 
x;t. x'ii) 
xx.x%) 
A':·C :Se·v·el 2 T rrr. 
Ger.eric 1,1ed cac: on 
 
:,:xx 
XXX 
 
xx.x%) 
:-:): 
 
XXX ( XX. 
XXX 
xx.x 
 
 
·•:zx 
 
:{. 
xx.x 
 
XXX 
XXX 
 
:o:.z 
X.Y.X 
Generic  ("Jed  cat 
on 
Generic  edicatiou 
xzx 
XXX 
:{X.}:% ) 
xx.    x%) 
:-:zx 
XXX 
( xx.x%) 
xx.x% 
z:-:;-: 
z;-:;.· 
xx.;,; 
X>:. X 
:o:x 
zxz 
;o•:.x 
:,x. x?;\ 
Ger::eric [,Jedicatio;; 
XXX 
XX.Xi;' 
xzx 
ZX.X'S 
ZZ:< 
xx.;-;%' 
xx:{ 
X}:. x'S) 
 
 
r:,e denominator for per:cer:tages is the r. T.De,c of patients ir. tr'.e ITT J?opulatior, fer each Treatrr,er..-t gro:.:.p. 
Note: Concomitant me,::::::_ca-:ior,s are those ;;it:1 a star-;: date 0:1 or after t.he first dose date of Treatr::ie:1t, or t:-wse t,·ith c. start dat.e before the 
::"irst dcse date c-:: Treat::nent 2::ci c. stop date or-, or afte:::: the first dose date a:: Treatc:-ie;-,t. 
Note: A patient may h2ve taken more tha:c c;;e rr,edicat.icn. The;:-e::"o::::e, t!"le su.,, of rr,eci.icac:ion ccu:1ts ar.d -ercentages :nay T'..Ct eq'...<al the total cour:ts. 
If  a  patient  had r::.ore  tDan.  one  :r,edica::ior:  .in a  category,  the  patient  is  cc,,.:.n.ted   once  in   t::J.at   catego::"y. 
[aJ  ;;,;no Drug Dicticna: 
iVersicn :,::-:) ,,,as ,_;,sed fc>r coding. 
 
Pro9"ramtr,i11:g:Jr:ckes': 
Note, that,- the   first  row-will   change   de'pendin;/  On   the    title.  :cf  -:t e<_titli::>  is,  ',Prio:t· -m d.i_cat;i_on-:AML -- ,then  ft is   1:_6   o)riq:,ute  _any _P_i:ibr  ?.ML 
 
 
meclicki'tion's-. If the title -is concomitant medication-AHL -then/the r-equired output is -to c_ompute- _any AML concomi:taNt.- medication-. 
Program Name: 
Listir:.g Source: 
Repeat for the fo:':.lo,-.:i.ng displays: 
Date Gene::"ated: 
?age x of y 
!able  14.1.14     Sur:-,r:;.ar-·   of     Concomitant Medicatior.s-non ,ruV;L 
;:, p-,'a-:-ior- 
Pa::ients with Ccmcc:":ti •,-.ar::.t 
t1edica-;:io'.7 
xzx 
xx.x?;.) 
xzx 
xx.x%) 
:-:xx 
>:x.x\ · 
zxx 
x:>:::.X½' 
A C Level 2 Te::::-I:1 
x:, 
xz.z%) 
XXX 
xx.xS) 
:•:xx 
xx.x',,' 
xxz 
xz.x%'. 


 
 
 
 
 
 
 
Table 14.l.lS 
SLlirh<,ary  o::  St'-.:Cy   Qrug   Usage  Ra-::e    Ir:ductior, Cycle 
ITT Populatior: 
 
 o..,t-yr,: 
(N   =  :n: 
 
Low CX-01 
= xxx) 
 
i-'!igh  CX-C)l 
{N   =  XXX) 
Cc ( 1;) 
 
 
 
·:::x-o: 
 
x;-::x 
x;,·. x':, / 
 
XXX ( z:,;. 
 
xxz 
 
xx.x 
 
 
-he  der,ominator fer  9-2rcentages  is  the  r.u.,2::er  of  patiewts  ,,:it:'.  nor:-rr,issing  da-::.a  ir,  tl"'.e  ITT  ?OfYcllatior,  for   each  Treatr:-,ent  g-rc,.::p. 
Study Dru.g T]sage Rate is defined as percer,tage of patiel".'.ts ,,;i::::. lCG½ dr·...ig usage '.-:hile en the stud·y. 
 
P:rcjrara,,-rting N6tes: 
For:things that -::lo ·.hot apply; 
inSert 
e.g. for Idarubicin ·+ CS,tarabibe arir,,. -t-XDl:.artct initial CX0-1 would-riot ·.apply. 
?rog::.-an Nar:-,e: 
Listing Source: 
Date Generated: 
Page x cf y 
 
?.epea:: for the fellowing displays; 
:=-0.n e  ·'"   : . :6 
S:..m<l"nac; of Study Drug Usage Rate !nd,.::ct.ion Cycle ;,;::-:r: Pop'-.:la::ion 
_:l_dd: 
Footnote: 1.r,e den,.Jc::,ina:.or for per-ceritc.:.ges is tie nLl.a,be::: of. patients ·,.,ith now-:,-.issing data ir, the :-:=r-r Population fer eacr'. Treatnent g.::-cup. 
 
Delete: 
Foo-::.:1ote: Tte ::ien-::i::,inator for percer::tages is the "-'-'-'•her of patier,::.s ;-;ith :"',ori-::n.iss.ing da:::a in the ='=·T ?opulaticr. for eac::L T:.-:eau;ier.t gro,..::p . 
 
 
Ta;)le ·  ,:1   l.  2-7  S;,;.,c'""ary  of 
Study  Dru.g   Usage  ?..ate  ?..e-indvctio:1  (7+3)  Cycle  Safety  Population 
Add: 
.:'n'1c.no::e: The de:-:.:::r:-.iwator for percentages is L;e :n;.,.,,ber .:,-'_:. pat.ien-::::s ·,;ith non-"'-iss.ing data in the Safety Fopula-::::io:--, ::or eac'."'. Trea;:.:nent grc-c.1p. 
 
Delete: 
Footnote: The der,..Jcc,ina::or for percentages is t:?.e n·c:..,tber of p.?.tiewt;s with :--,on-rr,.i.ssing de.ta .in the :T':' Populati.on fer -:?ac:, Treatment gro;,;.p. 
Inciuc-::.ion Cy-c2.e Compl.::_ar,ce ?.ate 
;, 
:-::xx 
zxx 
XXX 
Initiel CX-01 
xxz 
xx.:<'!:) 
:-:xx 
XX.X'i', 
x :x 
xx.x 
'C"'_.,..,,,..,, C' ,-, 
XXX 
xx.;-;:':; 
x:..::x 
xx.x 
XXX 
xz.z 
Cy-::.arabine 
XXX 
x;-::. x': 
XXX 
xx.x"i) 
xzx 
xx.x 


 
 
 
 
 
 
 
Tab:e  14.l.·'1  sw,s-1.s.r::· of 
Study Drug Usage Rate Re-inductio::i (5+2; Cycle :11 ?o;n:.lation 
 
 
 
Table  14..   lS   Su:rcr:-,ac-:  of 
St-:.:.C.y   Drc:;g   Gs age    Rate  Consolidation  Cycle l  Cycle 
?opulation 
P..dd: 
:·JcJte to ?rog:::ars--rte . 
would not apply. 
Re:rc,cve   Idar:..::bicin.   For    !1ings   that   cio r.ot   appl ::1  ,           insert   "-"    e.g.   £or ::::darubicin   +  Cytarabine   a.::E,,    CXOl   and     initial   CXO:. 
 
Delete: 
::-:icte   to    ?rogra::-- ,,e;::   For   thir.gs  tl'.:at  do   not   apply, i;-;sert  "-" 
e.g. for ::::dar-:.:.Oicin + Cytarc.bir,e ar;r,, CXCl and initial CXCl ;,could ;-;o:: c.pply. 
 
 
Table  l4.l.2D   S:.:.,c::1ar··  of 
Study )rug <)sage Rate Ccnsolidatio::i Cycle 2 Cycle I'='T Popc1latio:::. 
Add: 
No::e to ?rc-g:::ar.,:ne;· Re2ove Idarubic.i.r,.  For  things  that  do :wt apply,  inse:ct  "-''  e.g.  fey IciaL1bicir,  + Cyt.aYabir.e  a::.-rr.,  cxo:. and  ini::i2l  CXGl 
would not appl:.' 
 
Dele::e: 
Note  to   ?::.-ogr2rr.:::e:::-:   For    ::::',ir,-;s   t:'.at  cio  not    apply, i:::.se::.-t  "-" 
e.g.  for :dar<J.bici:n  +  Cyt.arabir,e  a.:::r,,   CZOl   and    initi2: CXOl  woc.:..ld  cot 
app::_y_ 
 
 
Table-   4  l.  21 
Su..:., ,ar·- of 
Stt:.dy Drug T)sa.ge Rate Inductic)n Cycle ?? ?opula::io:-, 
Add: 
Footr::ote: 
 
Delete: 
T:'.e cienominator fc:::- perce:-.tages is the nu.mber of patients ;-..·ith ncn-rr,issir,g da-c:a 
tl-:e ?? ?op·ulation 
for sc:a,..h T c::..cc,e" g:::o·_;,,p. 
Footnote: The cienc-,-:Iinator fo::: percentages is t.he nurrbe;:: of patients ;;it.h :-,cn-missir,g G.at2 in t:-',e ITT Population for each Treatrr,er.t groc.:p. 
 
Tab.le ·4 
Add: 
22 Sc.u,c:r,ar,.· of 
S::,:.ciy  Drc.1-g Usage Rate Re-in:foct.ion (7+3) Cycle P? ?cpc:.lation 
7--.,o:.no,.e: 
0.e n ,,.,.;.""'- '--o _.._  for 
percentages is the nw-c.ber of patients 
 
Delete: 
,·ith _.,,..,,.,_--,,i S'-i '"'9 data 
the 
PP Populatio;-1 for, a- : • .re-:-7:er.- g-r-01..:p. 
Foo::note: Tr',e G.e:::omin2tor fer percentages is the 1;.urrbe-r of patients ·,rit:'1 :::on-rnissir-,g cia::a .:.n tr',e "'"7'7' Popc.-::lation for each Treatment gro·cp. 


 
 
 
 
 
 
Table  14.1.23  SU:.1irr,ar·,·  of 
Study Dr;;,,g  Usage Rate ?.e-ind:..::ctio:-i. (5+2) Cycle ?P Populatior. 
Add: 
Footnote: Tt'.e denominator fc.::- percen::.ages is tt:e r:c1.-r.ber of patients ·.-;ith :-::on-nissir,g data "" t:",e pp ?opulatio:c for each Treatment grc:.1p. 
 
Delete: 
Foo::.r,ote:  'E1e  ds:, •-..:r.: --ate:::-  fo::::-  :=,er-cen.tages  is   t:-:e  ::',c.i...-nber   cf     patients ·;1ith n.'.)r:-r:,issing Cata 
::.he IT:- Po:'."'u'at-i , for each Treat:,rien; grot.:.p. 
 
?able   "'"     . 21J      Su.-rmar·,,   cf 
Study   Drug   Usage   ?..ate   Cor,solid2tion   Cycle 
Cycle   ?P   Popu2.a":ion 
P.dd: 
};ote   to   ?rogra,rEne.:;,·:   Remove   :i:daru:Cicir..   For   tl'.ings   t;:-;at   :io   not    apply,   insert"-",  e.g. for Idarc:c~c-_, 
Cytarac_,,e ar-, cxo=. a,1d i,1.:'.tia:.. CXOl 
>•muld not apply. 
Footnote:   The deno;ninator   for   percentages   is   t::--;e    r,-1:-:-bel'."   ,:;f    patients   wi::.h   nor,  missing   data. ::.:-:   the 
?P Population ::':or eaci: Treatme:-:t grcc:p. 
Note: Duratior, of expcsure calcula":eC as (date of las:: dose - date of firs::. dosei + l. 
 
Delete: 
Note to  Progra.rm:1er: For  ti1ir,gs t:"",a.-::.  do   not 
apply, .'...:--:ser:: "-", e.g. for ::darv.bicin + Cy::arai::ine arrc,, czo: a:-:.d initial CX-'.}l -.w-:;ld -:".ct a:::,p2.y. 
Footnote: The denominator for percentages is the r::.L--:-.t:er of patients ,,,ith :--,-:m-missic1g dat.2 ir: the .,.,,,,, Popula· icr, for each Trea::.:nen.:: grot:.p. 
St;;:dy Drug :Jsage Rate is defined as percer,tage of pa":ie;--;ts ,rith 100'6 drc:;g usage while c;;. t!""',e s::c:.ciy. 
 
 
Table  14.l.25  Su,-·nmary  of 
Study Drug Usage Rate Conso.lidation Cycle 2 Cycle  PP  Pop;;.la.tion 
Add: 
Note 'c.o ?rograr::c,,er: Remove  Idarc:bicir:. For ti'.ings that do not apply, insert "-" e.g. ::or Idart::.bicic "'" Cytarab.'.:.ne ar-rr,,  CXOl  arni initia::. CXOl 
·..;ould not apply. 
Footnote:  The deno:ninato!'  for   percentages  is  -::-.he  nu,c-.be.::- 
patients, .. itr. r.cr,-missing data ::_:,. ::l',e ?P Population for eacr. Treatme:::it gx-o'-.lp. 
 
Delete: 
:,:ote  to   Prograr!",me,::   For    things  ::'.":a::  do   :-r.ot   apply,   insert  "-",  e.g.  for Id&r'-lbicin  +   Cytara;Jine  ar:;-,,  cx,::i::..  and 
i:ritial CXOl would r:o:: apply. 
Footnote: Tie deno,nina-cor for per.cectages is the n,.::.,-.ber o:: patie:-r.ts ,,ith nor,-:nissing data i:1 ::he ITT Population fer- each ':'reat:..:ent group. 
 
 
TaDle  l4.  1. 26  Si·nrnary of 
Study Urug 'Js2ge Rate I:-::ciuctior, Cvcle Safety- Populac:ion 
Add: 
Footnote: The denor.,inator for _percer::t.ages is ::he nu.rr.ber c,.f patien-::.s wi-:::-.I', non.-rr:.issing date. -~ ::r.e Sa::'ety ?o;:n..:2-c.t.icr1 fo-r each Trea'c.r:o.eut group. 
 
Delete: 
Footnote: The deno:ni:iator for percentages is the nu:-r.ber cf patients with :::o:,-missing date ::.ri -:he ITT ?opulatio:1 for each Treat:nent gro-c;..p. 


 
 
 
 
 
 
Tab:ce 14     2; 
Sur,t..--nar'/ of 
S'c:udy  Drug  Usage  ?.ate  ?.e-ir,duction  !7+3/  Cycle  Safety  Population 
Add: 
Foot::io::e:   The  denominator   i'cr  per-centages   is   the   nu."':'l::er   of    pa-::ients ,.,-.-;_ th 
:-ion-missing  da::a  _:_n   the 
Safety Population for eac:-', Treatrc.er.-:: group. 
Delete; 
Foo:::c.oc:e;   :r:e  dencminac.or  ::"or   percen"':ages   is   the   r:u..,--:\ber   o;.:  patier:;"'.:s  ,,ith ;:;on-missing data 
the :T? Pop'..llaticn for eac:J. Treatme:-,t grou:;::•. 
 
?able   2.4 ..     28 
Sill:crr-,ar·.- of 
Study Dr1..;g  Usage Rate ?.e-i::.d:J.ctio:1 (5+2;, C:  c l e   Safety  Population 
P..dd: 
Foctr,ote: ".e derwminator for percentages is the r:ur:-,ber 'Jf pat::.ents ·,rit:h ::-'.or:-:rro.issing da-::a ir: the Safety Popula:::ion fo::: each ' rea::rr,e;;.t group. 
 
Delet:e: 
Fc,otnote: ne denu:ninato;:- for percen::ages is the r:,..;;:-,.be:::: of patients -,:i;;:h non-Eissir:;g data ,,., the ITT PopGlatiou ::"or each TreatEer,t g:roup. 
 
Table 
29 Su."'-0-a:::y of 
Add: 
Stud;:-·  Drug  Usage  Rate Cor;soli6.ation Cycle 
Cycle Sa::"ety Pop:..;2.atioc: 
c'<ote to ?::::og::::a;:-t!t.e1:: ?.eEc;te :da:::ubicir:. For things t:'1at do ::-,ct  apply, ir:s,:c::::t  "-", e.g. .'.:sr  Ida.::"Jbicin + Cy::arabine arm, CZOl aud .:.ni..tic.l CXC.l 
would net a.pp.:.;:-·. 
"'oo;;::1cte: T:',e denc::,inatcr for percentages is the :,u:'i'J:,er of patie:r:ts ,.,:it:, r:;on-;r,issi..r:g data in ;;:he Safety Pcpu.:.a"'.:icn fo.::: each Treatr::er:t grou)?. 
 
Delete: 
Note to ?.:::og.can-;,.er: For  things  ti-',at  do  not  apply,  ir,sert  "-",  e.g.  for  Ida::::'..lbicin  +  c:rta.::abir:;e  an:1,  C:-'.Ol a::.d  :i.:-:itial  CXGl  ,,oul6.  no::  apply. 
Foot,:ote: The dencmir:atcr fo:.c percentages is the ;,urnbe;:- cf patier,ts ;.,citi-', r:;on-rc:issing data .'c::-, ::he ITT Population fo::: each TreatE,er:c:: g::::oup. 
 
 
Table  14_;    3Q  SuIG.:nary of 
S-:1.:ciy Drug Usage Rate Consolidation Cycle 2 Cycle Safety ?opulatior, 
.;6.d: 
Note  :::c   ?ro:;:::a:r:rr:e1·:   Remove   :darubicin.  Fo::::  things  that  do r,ot  apply, ir-;se;:"-:::  "-" 
e.g. fo.::: :ci.arubicin + Cytarabi-:-,e arcn, cxc::. ar,d initia.:. CXGl 
,,,:ould not apply. 
?oct:note: '='he denominator for percentages is tr.e r:;u..,--nl::.:er of pa.tients ,·it!'. nor,-rr,issir:.:; de.ta .,.. ::he Safety Pop;,;.latior: for eac:'"l T::::eat,c,er,t group . 
 
Delete: 
•lote to ?.cograrr.me;,:; ?or ::hings t:1.at de r:ot apply, ir-:sert "-", e.g. for ::cia.rt:.bicin + Cyta.:::abine arcn, CXOl a,,c i:-,itial CXCl wouid sot app:y. Foo:::no:::e:   '::he   
denc-Einator   :i:c.:::   pe::::centages   is    the    r,u.7.be::::   of     patients,   ..;-ith   non-,c,issir,g   dat2.   in    the    ::r:r   Pop'..llatior_   for    each   T::::eatrr.e0.t   group. 


 
 
 
 
 
 
 
Tab::.e  l,G.1.31 
S1.1c-;:.,..ary of Treetmen-c Exposu:ce by Cycle 
Safety Population 
 
 
 
:nd'.lction Cycle T::::eatr.,e:1.t Ez3x-s·_;_re (Days) 
n 
 
::or,t:::ol 
(N = xxx\ 
 
;.:;;;,: 
 
Low e>::-Ol 
(0: = XX;{) 
 
 
XXX 
 
;:.,; gh    CX-0" 
{N 
xzx) 
0 
 
x;-:x 
r:-:ean 1, s . d . ) 
mediar, 
x>:.x ( .:-::-:.xx) 
x.x 
xx.x 
xx.x 
;,;y. xx) 
xx.xx 
xx.:,; 
xx.xx; 
Din 
xx.;,: 
rrcax 
xx.x 
xx.x 
xx.x 
xx.x 
xx.z 
?a.tient with any dosage ::.nterrup'.::io" 
Proportio;, of patier::ts -",::c ::eek 
Idar,.;bici:r. for less than 3 days 
Proportion of pat.ients ,,,;-,o toc-k 
XXX 
 
Y.XX 
:,:x. :,:'!;) 
 
xz. ;,;:\; 
:-:xx 
 
XXX 
xx.x;,·1 
 
xx.x% 
XXX 
XXX 
xx.xS', 
Cytarabine for less t?:an 
days 
:s:xx 
;.;;;. ;,;% 
xx:,;: 
:-:x.;z;; 
XXX 
ZX.x·' l 
Proportion of patients 
o did net 
take initial CXOl 
?ro_portion of patients ,-.-:io -::ook CXOl 
 
xxx ( x;:. x"o ·, 
 
XXX 
 
xx. 
 
XXX 
 
xx.;:'o' 
for .:.ess than 7 days 
Proportion of pat::.ents ,.,,-:-.o took less 
medicatio:r, in terr,, of recr.;.ired 
du.:::-ation (any of :;: a.rubici:1, 
Cytarabine, initia cx-o::. '3.nd cx-.J::.; 
XXX 
 
 
 
 
 
XXX 
xx.x%1 
 
 
 
 
xx.x'o1 
XXX 
 
 
 
; xx 
xx.x%) 
 
 
 
xx. 
XXX 
 
 
 
;-:xx 
xx.x-'o; 
 
 
 
xz. y; 
 
 
Ihe denomi,.ator for percen.t2ges is the nu.,--rJJer cf pa.ti.er:."'.:s w::..th :10:1 rr:issir,g- data in the S2fet::,, ?opulation fo::: each '::"reat.ment group. 
Note:  Durat.:.on  of   ezpcsure  within  a period  is  ca.lcu ateci  as  ida:::e  of   las"'.:  dose  -  date  of :'i:::s--:  dose)   -"-   l    for 
t:'wse d:::ug  that ;.;e:::e  ad,,i.nistereci 
across  different  ciays  ar:.ci  as    .-  day    for 
c.hose-  dr:..;g  a-'.i."niniste:::ed and finished within the sa:ne day. The swc: of these duration expcs;;.re within 
a. period would form the d0.:-a'..:ion of ezpos,,,re '.-Iit"c.in a cycle. 
Program :,;Jame: 
Listing Source: 
Da'.::e  Generated: 
?age 
of y 


 
 
 
 
 
 
Table 14.1.31 
St'..L-rr,arv of Treat,ner:t :Sxposure by Cycle 
Sccfety ?Opcilatior: 
 
 
 
Re-i::1ci1.:ction (7+3) Cycle Treatrr,ent 
S>:;:-os re :Days'. 
::ontrol 
Lo,.,,- CX-Dl 
(N = xxx:, 
'"'.    ::;-; 
( 'i'.-) 
 
Hig;",  CX-Gl 
\:'1   =  xx:s:· 
{ % ) 
;-:xx 
XXX 
xzx 
:near,   !s.d.) 
xx.x 
..  Z.>.1./ 
:•:>: 
:{x.xx:, 
xx. x;-:: 
.XX) 
mediar> 
L,::_r: 
:nax 
?a::ie::·It with any ciosag-e interr-,;.ptio:1 
?rc-por:::ior: of pat:: er,ts whc took 
ICaru.b.-i_cin  :'or  less  tha:1  3  days 
?rop<:;rtio;:-, of pat.i.er:ts ,,.,ho ::ock 
C::rtarabine   fo:r   less   tha:1  7 days 
?:roportic:-: of patie:cts s-;hc did not 
  ? A i ti=l rVQ1 
?rcpc.:::-ticn of patients ;;to took CXOl 
xx. : 
XY.  ;{ 
XX. X 
XXX 
 
xx: 
 
:-:x;,: 
 
:-:;s:z 
 
 
 
 
,._•. ?: 
 
 
>:x. xi) 
XY .z%i 
xx.xs ·, 
x:-:. Y. 
:-::x.x 
XX.Y 
XXX 
 
xzx 
 
xz:--: 
 
xx:--: 
 
 
 
x;s:. x'i'.· 
 
 
 
 
 
xx. 
xx.x 
xx.x 
xx.:--; 
XXX 
 
 
XXX 
 
XXX 
 
;-::x:--: 
 
 
 
xz. ;{·:,._ 
 
xx. 
 
xz. 
 
z . x, 7 ' 
for less than 
days 
:-::xx 
xx.z,, 
XXX 
xx. 
XXX 
X>:. x%; 
?:r::>portion cf patie,1ts whotook .:.ess 
medication i::,. terrr.s cf eqciired 
dureticr, (a::iy of Idarub cir:, 
(':/tc.rabine,   initial   ex-l   andCX-01) 
 
 
 
 
XXX 
 
 
 
:•:x.x%) 
 
 
 
XXX 
 
 
 
;-:z.x'o) 
 
 
 
XXX 
 
 
 
 
xx.x%' 
 
 
The denor::inato:::: for 90rcentag-es is t:',e rn..L"CT.be:::: of 9a-::ie:1-:::s -_.,:.th nor: 2issir:g da:::a ir. the Safe::y Popt:.lation fo:::: eacr:! Treat;-r:.ent grou,:::·. 
Note: C•uratior. of  exposure  wit.:-::ir.  a  period  is  ca::.c,  ;lated  as  (da  7.:.e  o::  ':.ast  dose  -  Cate  of  fi.:::st.  dose)  +  :.  fc::::  -::.h8se  d::::c1g  c.hat ·"·ere  c.d,,inistered 
across diffe=ent days ar.d as l day fer tr'.ose drug ad.7ir:istered a:1d fi,,ished withi:1 tl":e same day. The su:n c:' these duratior. expos"Ll.re ·w·it:"lir.  
c. pe::'.'iod wc'.lld  fo:::-r:,  t.he  fr0.!.""aticn  of exposure witl"".i:1 a cycle. 
Progrell'. 1''.c.;-r,e: 
Listing Scu.:::ce: 
Da o  Ge,..,ora,-od · 
Page x of 


 
 
 
 
 
 
7able l4.l.3l 
Sur:unary of T.::::eatrr,ent E:xposure Cy Cycle 
Safety Pop"-"lat.ion 
:::or,t.::::ol 
(N "" xxx) 
 
.:..,O'-··' CX-01 
(N = XXX) 
 
'-<' gh CX-Oi 
xxx) 
  
n (%/ 
 
?.e-inductio-r;. 15+2) Cycle T.::::ea-cment 
E>:poso..:re (Days) 
n 
XXX 
:u:z 
XX>" 
:-r,earc (s.d. 
median 
t.""c:..n 
x:-:.x 
ZY..Y.Z) 
; Y.. 
xx.xx) 
xx.x 
xx.x 
xx.x 
x.zx 
x:.-:.xx) 
 
X 
max 
xx.:,.: 
XX.:-' 
x:-:.x 
Pat.ier1t ;,:.:th &n_y dosage ir.::er.::::0p-:.ion 
?roport.io:1 of pat:.ent.s ,,:no took 
IC.arub.::.cir:.  to.::::  less  tt:ar,  2 days 
P.:::-oportion  of   pat..1.e;-its  ·,-,::to   toof: 
Cytarabine  fo.:::-  le:ss  -:ta;;  5 days 
?.::::opor::ion of pat .er1t.s ,..,r:_o d.id r::ot 
c:.ake i;-iit.ial CXOl 
?roporticn of pat ·.e:-J.t.s ;-,c "'.:oak CXGl 
fo.:::: less than S days 
Proport.ior:. of patc.er,ts ,.,.-io -coo:-: less 
medication  in  te::'.T.: 
cf 
equi.::::ed 
duration (any cf ::: a.::::ub c1.:i, 
Cytarabir::e, ini ti2. ex- ::. a:::.d CX-Gl) 
xx;.: 
 
:,:xx 
 
:o;:;-; 
 
 
 
 
 
'.XX 
 
 
 
 
 
XXX 
xx. x%) 
 
xx.x%} 
 
xx.x 
 
xx.x%\ 
xx.x'b) 
 
 
:-::x.x"c) 
x:-:;-.: 
 
XXX 
XXX 
xx·•· 
 
XXX 
 
 
 
 
 
XXX 
:-::.,:_z:.;; 
 
x,:.xs; 
 
XX. )C'.' 
 
 
xx. 
 
:-:x.x'o·, 
 
 
 
x:--:.;.:%' 
;_;.;y 
 
 
XXX 
 
 
XXX 
 
xx.x 
xx:,: 
 
 
x;-::-: 
x:-: 
 
 
 
XY.z\: 
 
xx . .x%\ 
 
XY 
 
 
 
x:,:.;-:-"c' 
 
 
Tt:e der:;ominat.or for percer:::ages is t:"',e nu.r,:cer o:: patients with r:on sissing da::a. in tt:e Safe::/ ?opc.:latior, for eaci Treatment group. 
Note:  iJuratior, of  exposure ·.,:ithin  a  perioci is  calc1..:lated  as   (date of last  dose -  Cate cf   first  ::iose)   .,_   l    for 
t.l---.ose drug that: ·,,er-e ad,"T,ir:is::ered 
across dif.::e::::en-:: days ar:d as  :;_  day 
.::o::::-  tnose dr"...ig   ad.--rtinistered  a:1ci.  :'inis ed :.-<ithir,  t:'.:e  sa:n.e  day.  The su.--:--,  :Jf   these d1.;.ratior.  expcsu:::e  ,.,;ithir: 
a  period :,·ou2.d fc:c-rc'.  the 
dclratior: of ez:posure withir: a cycle. 
?rograra Name: 
Lis ting S01..:rce: 
Date  Generated: 
Page 
of y 


 
 
 
 
 
 
Table  2-4.1.31 
$;..m',:riary cf Treatment ,:posure by Cycle 
Safety Popul tio,, 
 
- or.t:!'.'ol 
1 IJ = :,:x;-:) 
 
O"w· CX-01 
\i:S = XXX) 
n {%i 
 
Big-:"i. CX-01 
(N =  xxx:· 
n ('o' 
Cor,soliOation Cycle 
Sxposure{Days) 
l Tr:-eatrcent 
n 
:o::x 
zxx 
XXX 
mean is.d.' 
z;.:.:,: 
xx.xx\ 
x:<.x ( xx.xx) 
:in:.xx ( xx.xx··  
median 
;,:;.,:.:,; 
:-:x. 
zx. 
in 
:-:z.x 
xx.x 
xx.x 
xx.x 
.x 
zz.x 
Pcctient with a:,.y ciosage interruption 
:,::<x 
xx.;,,;•, 
:o:x 
xx.x;:,·, 
xzx 
:-:x.x%) 
Proportion of pa::ients who tock 
Cytarabine for less t!",arr 3 days 
·-:x;.: 
xx.'.{',: 
XXX 
xx.x'?) 
;.:zx 
·-:x. xt 
Proportion of pac:ients who did :wt 
take ir.itial CXOl 
,.opor:-tion of pc.tients ·,;ho took CXOl 
for less thaw 5 dc.ys 
?roportior. of patients whotook less 
rr.edicac:ion in terms o::. equired 
duration (ar.y of I-iar"J.D cin, 
:,:;,;x 
}G:,x'i_,' 
 
xx.xi) 
 
 
XXX 
xx.x% i 
 
xx.x% 
XXX 
 
 
XXX 
xx.xz,; 
:,:;,, 
Cytarabine, initial ex- l and cx-0:1 
'{XX 
:-:x.xS) 
x;oc ( xx.x%) 
XXX 
;.:x.x%) 
 
 
T:1e denominator for percentages is the n:..1..."°:'her of patie;1ts ,.:it'.', non missing data in ti:.e Safety ?opulatior, fcJY ,22ch Trea:::mec'.t group. 
Note:  Dur:-ation  of  expos;..:re  within 2    period  is   calc'..llated  as   (Gate  of last ciose 
Cate of first: dosej + l ::.or t.hose drug t:',at ,,:ere ad,c,inistered across   
differ:-en::   dcys   and  2s   l    d2y  fer    tl1ose   drug   adc..  ,ir;istered   a:.d   finished   wi·t:':!ir.   the     same   day.   Ihe    su..:;;  of     these   durc.tior:.   exposure   witf::ir, a period 
would form tI":e dura:::io;,. o: e•:pos'-'re wit:::in a cycle. 
?rograrr: Ncme: 
Li s -i-.g <::ou.,.ce· 
Date   Genera-::ed: 
Page ;z of 


 
 
 
 
 
 
Table 14.1.31 
su.,:rr,ary of Treatr:ient E:.-:posc.:re by Cycle 
Safety ?opo_.:.lc.'.:ion 
 
{ 1    = xxxl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
,.:;e  der).cr:;icator  for   p'C:rcer>.c:ages  is    t.he  m.:.,,cDer   of    patie:1ts  s-:.it;;.  r,o:n   missir::g  da:::a .:.r:: the 
Sc.fe::::y Populatior. for each Trea-.:::icen-.:: g::-ou;:. 
:(c-te:  Dura.tier;.  of  exp :-s'...:..re  ,,;.ithin  a  period is  calculated as  10at e c-f  last dose  -  Gate  of  first dose: 
l for those drc.:g c.hat ,,-ere adrrdr::.is::.ered 
a.cross ci.iffe::-e:--.-.:: days ar,d as l day for tt:ose drug ad.--:-,i:-:;istered ar,_6. fir.isied ·,:ithi:-: the same day. The SW-'7. cf these du::at.ion exposure wit:h.i:-- 
2 perioci. wc;.;.ld f2r2. the du::-aticr, of e;,:pc;sure witr.i::1 a cycle. 
Program Name: 
L'"'-;-i,-,g Sr,i_;_,.:e· 
elate  Ger,erated: 
Page x of 
:or.trol 
(N "' ;,:xx) 
n (%) 
Low 
iN   "' 
n 
CX-Cl 
xxx;, 
( % ) 
Ei;h CX-Cl 
(%) 
Consolidation    Cycle 
·-r"'-a """""' 
Szposure (Da::is) 
KXX 
r:'.ea:r,   (S.d. ': 
xx.x 
x;.,-. ;,:x;, 
%XX 
xx.x 
xx) 
x;-:z 
;-:x.xx { xx.xx) 
17.edia.,, 
xx.x 
xx.x 
rr.c.x 
xx.:.-:: 
xx.x 
.x 
:.-:x. 
;-:-:.x 
:.-::x:.·-· 
xx. 
?atie:n::   •,;ith   ar,y  Gcsage   interr,..1pticn 
x:,;x 
xx. x%) 
Propo.rtior:. of patients who'.:ook 
·-::-:x 
xx.x'.i; 
xx;.: 
xz.x':,J 
Cytara:Oine   for   less  tha,i  3 days 
XXX 
xx.x%) 
?roportion of pac:.:: er.ts ;;ho did r:ot 
  akA  i " ia! cxo 
XXX 
x:.-:.x'c 
Proportior:: cf pc:.t:'.ents ;-,;ho took C:;{Ol 
XXX 
XXX 
:.-;x.xs·, 
xx.x": 
x:-:;,: 
x;-:. 
x;,:>: 
xx.x%l 
for 
less  "'c.han  5  days 
XXX 
xx.x :) 
zx:,: 
xx.x-?\ 
xx.x\·: 
Proportion of pati.ents whoc:ook .less 
:r,ed.:..cation  ir:. terr:-.s of 
equired 
duration (any of :.darub cic, 
Cytarabine,   ini'.:ial  CZ- :;_   a:1d  CX-01) 
XXX 
xx. 
zx:s: 
xz.z's) 
:o::s: 
z. 


I
 
 
 
 
 
 
 
Figure 14.2.l 
Ove.:::all Sur,rival plot 
'<''T' Populatio,, 
 
 
C 
 
3 
.£· 
C 
C 
; 
2 
c, 
: 
g _; e ---------------------------- --_J 
0 
20 
40 
60 
80 
,oo 
Number of Days fi-oin Baseline 
 
:".umber at Risk 
fda···C; -1a 
xx 
X.X. 
;,.ex 
xx 
;,_:,; 
xx 
lda+C;-ta-'-low CX01 
xx 
xx 
xx 
xx 
xx 
xx 
lda+Cyta+hig:h cxo l 
xx 
:,;x 
= 
xx 
X'<. 
;,,:...,_ 
 
 
?rogram Name: 
!.-isting Source: 
Repeat for the following displays: 
Date Genera::eci: 
?age x of y 
Figure 14. 2. 2 Overal Survi;ral plot :.'ETT ?opulatior, 
 
Fig"Jre 14.2.3 Overal.'.. Survival p::..ot ?P ?opc:.latio,, 
ld,1 
CX(Jl 
ld,1, (  ::cm '·hiti!l CXO i 


0 
 
 
 
 
 
 
 
,;g,:.,,.e  14.?.L 
CIF plo': fo.:::- e-,,en.:: f.:::-ee s;.:::rvival (f:-::orr: date of randc izaticn) 
.,.,,..,,..  Population 
 
 
 
0 
 
 
J  
0 
0 
0 
..Q 
0 
1 
0 
 
 
c, 
0 
 
 
0 
0 
 
 
lda+Cyta 
Jda- c:-1a+10 \ CXO! 
lda i-(':,.1a- high CXO I 
 
 
 
 
 
 
 
 
 
 
 
0 
20 
40 
60 
80 
100 
 
Number of Days from Baseline 
 
:\"umber at Risk 
lda+Cyta 
xx 
xx 
xx 
;,;;,;: 
xx 
;,;;,; 
Jda+Cyta+ low CXO I 
xx 
l\.."X 
xx 
X."X 
xx 
xx 
!da-.·Cyta+high CXOl 
x.x 
:,;x 
xx 
x_;,; 
xx 
x_.._ 
 
 
Prcgra:r:-, Name: 
Listir:.g Sou:cce: 
Repeat :for t:'"le follm,ing displays: 
Da e Gene:ca..::ed; 
?age z of 
·j
-


/"
f, / 
 
 
 
 
 
 
 
Fie,;,,.,., 1L.?.:::; 
I 
i r=-- 
-VJ'i 
c::F plot for event f.cee surv·ival ,'.fro:;r: Gate of :::-ar:do:nization/ Q' l?op,tlatio;:,. 
S,5 3/2 if If 
 
Figure ''1 2. 5 CIF p::.ot ::':or  lec1ke:aia  free  s:.1rvival  IIT  Populatic:•L 
Figu;:e   14.2.'    CIFpiot.  ::':or   le:.1kemia  free  survival 
?opulatio::1 
Figure J..4.2.8 CIE' plot fer r.eutrophil (>500) recoste:::-y (frmn date of rar.do:r,iz2-::ion) I':"T Pop:.ila's::ic:i;,. 
 
t=.gure  ::.4. 
9 CIF :pJ.ot for platelet ">2000C} recovery (from date of rando2ization) I'.:-7 Pop·ula-;::i:::r Figu:::-e   J..4. 2.  
lO    CIF    plc.t   £:er   ::eu::rophil    (>1000)    r eco-:..0  e  r  y     (.fro:2.  date   of  :::a:1ck:2.i::aticr,:,   :rT     Pop1.1latio" 
Figure  14 
CIF     plc,t   £or   pla.telet    f>l00000;    recovery    (f.co:.1  date of  rar.Co,c,i=a.::icr,) 
;::,opulat::.on 
Figur-2 
CE' plct :'.or Ye:l.apse rs,orphelogic C?:\ .,...,,,,. - c;iw.::.a .:.. ,. 
E"igu.re 
n.2.~3 CIF plct fey relapse 1c omp c s .::.t e  CR)  I':'T  ?opulatior, 
Figl:.:::-e 14.2. "L: CIF plct. ::er relapse 'corr.posi.te CR) tC'f:"'l ?cp,..ilation 


 
 
 
 
 
 
 
Table  14.2.l 
Primary  Outcor:-,e-CR 
-,--,.   0vL'.ac..,.,'.l 
 
 
::antral 
(N = xxx) 
n (%) 
Low CX-01 
(N = xxx) 
n (%) 
High CX-01 
(N   = xxx) 
n (%) 
?..chieved   CR 
XXX 
,.x . .. 
:-rnx 
x. :%) 
 
xzx 
( x :.z } 
 
versus Ccnt:co:. 
?ropocc:ion Difference 
70'o C0Efide0ce Interval [a) 
p-vali.:e [b] 
 
 
x.xxx 
>=. xx, 
;,; . >:x: 
.xx:•: 
 
 
x.xxx 
"z. ;-c-:, X. x;;: 
x.xxx 
 
 
 
fa] Based or. Exact. Bir,omial (Cloppec: Pearson) Co:-,fiden·::e :Z::1t.e:::7al 
[b} One sided ?ishe:r Exact Test 
?rcgrar:: Name: 
Listing Source: 
Repeat fer the fo.llm,1i:::.g displays: 
Date Ger,erate:""! · 
?age x of 
Table 14.2.2 
Tab:e 14..c:.3 
Table 14.2.4 
Delete: 
 -'- rr.o-'-i C- tco-.."'-r;:,  ,._,,-..,.T nv ,,!a ;;.o,.., 
 
Prirr,ary Outcocc1e-CR ?? ?opulation 
Secondary Outco;ne-C:-ti ITT ?opu.lation 
Footriote:    (a]   Based   or"  Exact   Bir,c ,ial    (Clopper   ?ea:-sor,)    Confidence   Int er-0,al 
IbJ One sided Fisher Exact Test 
 
Tab2.e 14.2.5 
Delete: 
 
Secondary Outcome-CRi -lITT Population 
2'ootnot.e: iaJ 3ased on Exact Bi:-,c:::,ial (Clopper ?earson; Confider::ce ::r::::erval 
[b] o e sided Fisher Exac:: Test 


 
 
 
 
 
 
Table 14.2.6 
Delete: 
Seccnd2.ry Outcome-CRi PP Populc.tio,, 
Footnote: '.aJ  Based  on  Exact  Binomial  (Clopper  Pea:::soni   Confide:c:ce  Ir-,::er-val 
[bl One side-::i Fisher Sxact Test 
 
Table 
. 2. 
Delete: 
 
Seco:i.dc.ry Ou-::corr,e-Co:;uposite CR ITT ?opv.lation 
Foot::1ote: '.a2 Based on Exact Binomial {Clopper ?ea:::so:1) Confidence I::",::erva.l 
[bJ One sided :!"isher Sxact Test 
 
Table "-'-.2.S 
Delete: 
 
Secondc::::::,, Outcome-Co:r,posite CR MITT Popv.lation 
Footncte: [aJ 3ased 0:1 2:,:ect 3io.o:-nial {Cloppe.c: ?ea:::-so:--,) Confidence ::::n'Cer·val 
L.OJ One sided ::'isher 2xact Test 
 
Table 14.2.9 
Delec:e: 
 
Secondary o·c1tco2.e-Co2,posite CR PP Pop:J.lat.io:, 
Footno::e: (a] 3ased on :Sxc.ct :Si:cwmial {Clopper ?ea:-so:1) Confidence In-:::e:-va· 
\bJ Cne sided Fishe::: Exact Test 


 
 
 
 
 
 
 
?able 14..2.10 
Mo.:::-tality Day-30 
::::T  Population 
 
:::ontrol 
{N = xxx) 
n (%) 
 
Low CX-01 
(N = XXX) 
n (%) 
 
High CX-01 
(N   = xxx) 
n (%) 
Death   by Day 30 
zxx 
x:-::.x'i} 
XXX 
xx. 
XXX 
.};"· 
 
Ve.:::-sus ControJ. 
Propo:::"tio,, Diffe:::ence 
95::, Con::'.de:-,ce Inte.rval [a; 
 
 
x.xxx 
[x.xx, x.xx] 
 
 
 
7..XXX 
xx, 
p-value [b] 
x.x:-::x 
x.x:-:x 
 
 
 
[aj Based en Exact Bir.orr_ial !Clopper ?earson) Ccnf:,der..ce Interval 
[bj Two sided Fisher Exact Test 
?.:::-ogram  :';ase: 
::a.te Generate- - 
listing Source: 
Repeat for the follo;,·ing displays: 
 
Pase 
of y 
Table 11;. 2. ll 
Mortality Day-60 
rcp'"'::_"'".:.o" 
 
Table l4. 2 .12 I<lortality  Day-SC TIT  Population 
Table  ::_4. 2 .13 
:-1crtali ty Da:y--3C: t-'.I'::"T Populatic:-, 
Table 14 .14 Mortality Day-60 t-ETT ?opulat.i,..,.., 
Table 14.2.15 
Mo::::r:.ality Day-90 ME? Population 
Table 14. 2. 16 
Mortality 8ay-3C PP Population 
TabJ.e 14.2.11 Mortality Day-6C PP ?cpulatior,_ 
able 2.4. 2. l8 
Mo::::t:ali t:y Day-9G ?P Pop's.:.lat:ion 


 
 
 
 
 
 
 
T2ble H.2.19 
Si"T>Ir,ary   of    O•ierall  Survi,,-al 
I7I' ?cpulation 
 
::ont.rol 
(N = xxx) 
n (%) 
 
Low CX-01 
(N = xxx) 
n (%) 
 
Hi.gh CX-01 
(N   = xxx) 
n (%) 
 
Patients Died 
;,:xx 
xx.x%) 
XXX 
xx. 
XXX 
.;,d) 
?atie:1:::s S-cill alive 
XXX 
zx.xS} 
XXX 
zx.x ' 
XXX 
xx.xS) 
Ti;r,e tc 'Jeath (days) 
 .1,,,r<' C>O" r"' 1 
xx. ; 
zx.x 
95So Cor,f.idence :nterva: for 2-.'.edian [a) 
25% and 75% (?ercentilesl 
-::-:.x, xxx.xJ 
xx.:-:}:, :-:x. xx 
[x:,:y   x,   xxx.x) 
x:,:  :-:x,    xx  zx 
[xzx.x, ;,:xx.x; 
x:-:. xx, ;-:y. ;-:x 
Range 'b" 
xzz,   xxz 
:-:,:·,:,   xx;, 
x:-:x, ;-;;,;;,: 
 
Vers'-'s Cor,::rol 
?-vc.l;;e    (Log-Rank  'Iio·S::: ·, 
;{. :-:xx 
XXX 
 
No e: Den:xninatoYs fo.:.· perce:1t2ges are based on the rn1..7ber of patients ir:. tf;e 
[2. r:cpl2:r:;-t,ieier estior,ates. 
[b Inc:·.J.Oi::g censcreC obser7ations. 
 
 
Pop\1la;::ion 
 
?:cograr:-, Name: 
Lis tin,; so,.irce: 
Repeat for t:--,e following displays: 
 
D2c.2    Generated: 
Page :-: of 
Tab.le 14.2.20 S·c1,.-r.rr,ary of Cverall  Sc:rvival  l.I TT   Po,::n:..:;.a::i.on 
Add: 
FClOt::.cte: Note: De:-wwir,a-::ors for percer-:.tages are baseC on t'.:.e nu.,Tsber of patieu.ts "-, the 11:ITT Popu:ation 
 
Delete: 
Foo::::.o-::e: Note: Deno,:;-,ina-;::o.::-s for percer,tages c.r-e based or. the nUEber of ;:;c.tients in t'.ne ITT ?opulation 
 
Table 
Add: 
.2.21- St:.""TET,ary of Overall Survival PP Popu2-ation 
Foo-:note: Note: Denomina:.::o::s for percer,tages are based on the nUEber of patients ::.n the PP Population 
 
De.lete: 
Footnote: Note: DE-nor::cin.-:,tors :t:or percentages are based or. t:le ni_.";_c-r-:ber of patien-ts in the ITT Populatior, 


 
 
 
 
 
 
 
 
 
 
 
Tirr.e Iriterval 
(Day; 
 
 
 
 
or::trol 
-:::,; = xx.:-:; 
 
 
 
 
Low CX-Dl 
( .] = XXX} 
Table 14.2.22 
Ssccrr,ary   of    Overall   Sur,ri 0,-a l 
ITT      Population 
 
nigh CZ-01 
(N 
X>'.X) 
 
:Ss-::.ima-::.e 
 
C 
0 
½Z½ 
;-.:z;-: 
XXX 
to 
;-.:z:,: 
XXX 
xxz 
8 to 13 
zxx 
xx:-: 
XXX 
l 4 :::c 21 
x;-.::, 
xzx 
;c-:z 
to 30 
zx:,• 
xzx 
XXX 
31 to 90 
XXX 
XXX 
XXX 
91 co 120 
XXX 
;-.:xx 
XXX 
<cort-;'"'ii"'d> 
 
 
 
 
Progras Name: 
Listir.g Source: 
Repeat =or the following displays: 
D2te  Generated: 
Page x of 
Table ::.4.2.23  ScllLLEiar"  of  c-v-e::-all  SurviTal -1 :Ss:::i ace  tHTT  Pop1..:l2ticr, 
Table 14. ~. 24 s,.;..--r£ary of o·verall Su::vival tc.,, :Sstir:-,ate PP PopI.<laticn 


 
 
 
 
 
 
 
T.-c:ble   14.   2. 25 
l'i2e  tc   ve::it  Free  s·o.rvival  -  Days 
'"'' "0?"7 "t; 0.., 
 
Cont::ol 
XXX) 
 
Lo;-; CX-01 
(N "' z:,:x;, 
C 
 
High cx-c:._ 
.\"c,       --       .,,..,.,.,,_>, . 
n ( 
 
 
 
; 
XXX 
z:-s:x 
xx:, 
No.::.,"7'.0er of pa::ien::s event free 
XXX 
xx.:,• 
xxz 
xx.x';;) 
::xx 
x:•:. >:', 
r-:uri.::,er o:: patients cer:sored 
zxx 
xx 
XXX 
XX.X·, 
XXX 
:-:x. 
 
2_·· !:-"'"'::::. "'·,· -· e 
x;-;:. X 
xx.--- 
.x 
;,·ec_a 
xx. 
xx. 
xx.x 
75· pe centile 
xx. 
xx.;.; 
xx.x 
?ar,ge inclc.,ding ce:1scred ·v·alues \ 
xxx, 
;-:x 
XXX, ZXX 
xxx, ;,;-:x 
Ra:-:;ge withO'Jt censored. ·values) 
xxx, 
{;{ 
XXX, XXX 
xxx, x;.:;-.: 
 
 
 
Program Ea:r::e: 
Lis ti.r.g Source: 
Repea:: for the following displays: 
Ja::e   Ge:1erated: 
Page 
cf y 
'cable 
 
Table 
Add: 
2.26 
Time tc Zvent Free Survival - Says LfiTT Pop·c1::.ation 
 
2.27 
Time tc Leuk.er:',i.a free Sur:7:.·,,al - Days {::':::-o;-r, rando:;;-;_ization) :TT ?opulat.i:-:in 
::,:ote   to    P:::ogram.·ne::::   ?.eplace   ever.t   free  ,.,.iti"",   leukemia   free 
 
Table  2.4. 2. 28 
Time t:::: Leukerr_ia ree Sur-,,i-.;c.l - Ja.ys (frorcc ::-a:.do:-s.';.;:ation) I•T?':: Pop:ilatio-, 
Add: 
:1ote to Programmer: Replace evect free v:iti": leukemia f:::-ee 
 
Table 
.2.29 Ti:ne tc Ne;;trophil ?.eco7e::'.'y \>5CO) - Days (from ::.-and.omizat.ion) :T':: Populatio:1 
.A.dci: 
i:.:Ote to Prograrr,mer: Replace event free wit.!'. net.:trophil recc-,,e:::y 


 
 
 
 
 
 
Table 14.2.30 Ti",e tc platelet Recovery  (>20000\  -  Days  (f:::or:,  rar;.dorr,ization)  
Add: 
:,..;ote tc Prograrr.ser: ?..eplace eve:r;t free Ki"'.:h platelet reco-,.rery 
?opu.latior. 
 
Table · .--31 :'i::te tc., Neutrophil  Recove:-:-y  (>l.CCO)  -  Days  ;fro-.::  randomization)  ITT Popu2.ation 
Add: 
:::ote to ?rograrc.r:10r: Replace event free with neutropf".il recove:::-y 
 
Ta8le 14 
Acid: 
 
Time   ts    platelet   Recovery    (>100000)    -    Days {froz,  rar,domizatior::) 
Pvp,.,lo..,.:.o.- 
: ate "'.:.o P:-:-ogra:;,.,'r,er: ?..eplace  evect free \•:.: t:1 platelet recove:-:-v 
 
Table 14.2.33 .t·:::.z,e ::c relapse (duration c::: :rr:orphologic CR) - Days ITT ?opula.c:io:, 
Add: 
c'.'.iote to Prograr:-.:r,er: ?.eplace ever:t free ._,;ith relapse 
 
Tc.ble   :'..4._.34   Tir:,e   -::o   relapse    (du.ratio,,   of   composite   CR)    -    Days   :::T:-    Population 
Table  C   4. 2.  35 
Ti::r,e 
E1:er.t E"ree Survi-:,_,al - Uays (frcn -a..,d.---,,,.,; ,,.,,o--.; O""') ?P Po9ul2tic::-: 
Ta:0}.e l4.2.36 T.:'._r:-,e ::c Leukemia ?ree  Survival  -  Days  P? ?opulatio:: 
Add: 
Ncte to Prograrr;:-ner: ?..e;,lace event free with 2-eukemia free 
 
ic.u_;_e   14.2.37    Tirr,e tc- '«:::-t::::-opn 
Recov-ery  (>SGC) 
Days (:'.:::::-c;n .rando;r:izatior,) ?? ?01>u.lation 
Add: 
c'iote to ?rogra::cmer: Replace event f.ree ,,;ith neutrcphil recover.. 
 
Table  14.2.38  Tic:ie  tc  platelet  Recovery  ,'.>2GOGG)  -  Days   (f:::-o:rr:   ra::idc:r,izac.ior,)   ??   ?op-..,::.atio;1 
Add: 
·Note to ?rograrr:.r:-,er: ::Zeplace event free ;d::h platelet :::-ecc;;e:;:-y 
 
Table 14.2.39 Tir;-,e tc-  Jei..;trcphi.l  Recovery  (>1000)  -  Days  {froEt  ra.::1domization)  ??  ?opi..;la,:ion 
Add: 
Note to ?rograrcmer: Replace event free ;-;i::'.", neutrophil reco;ter--.· 
 
Table  14.2.40    Tir.",e   to    platelet Reco'ter/  {>lOGDGO} 
Oays (from ra:ndornizationl  PP  ?opulation 
Add: 
Note to Prog:::-arr;rr-,e::::-: Replace event free 'With platelet recc;terv 


 
 
 
 
 
 
Table l4.2.½l Ti::rce tc rel2pse -'.dura-:ion of morphologic CR) - D2ys PP Pop-..;latio;,;. 
Add: 
Note to Progra2.c--ner: Replace even-:: free ,. ith relapse 
 
Table. · .;.   c:..½2      Ii,;;.e   tc    relapse    (d:..::rac::ion   of    corr,pcsite   CR)    -    Days??   Popu2-ation 


 
 
 
 
 
 
 
T2;)le   -,i       2 "3 
ScJ.bgroup  Analysis-CR 
:::"c':'  ?opulaticc. 
 
::ontrol 
(N = XXX) 
n (%) 
 
Low CX-01 
(N = xxx) 
n (%) 
 
High CX-01 
(N  = xxx} 
n (%) 
 
Ageg.::oup: < !'J 
 
XXX 
 
xx.x°f' 
 
zxx \ xx.x%! 
 
XXX 
xx.x%) 
95 , Confi::ience :::r.t.e.::vc:l 
Age group: 2 c .:, 
95? Confider,ce :::,,c.e.::vo.::. 
(x.x>: , x.zx·, 
XXX 
·-·x.x-e, 
(x.z 
;-:.x:-::, 
\Z.XX , X.xx;, 
XXX ( XX. ,,:':s 
(x.xx , x.zx.) 
;x.xx, x.xx) 
xxx ( xx.x%:, 
(x.xx, x.xx) 
 
A1'::..: Ve QOVO 
 
xxz 
 
xx.xS 
 
:-:xz 
 
xx. x001 
 
xxx ( xx.x%/ 
95% ConfiCe,1:::-2: :--::.e.::,·:c: 
Ai•L: Secorcdary 
95½ Cor::fiO.er::ce '"'~e::::,-2 
(x.xx , x.xx\ 
xxx( xx.x%; 
(x.xx , x.xz·: 
(x.x 
X. 
xz:-: ( xx.xSi 
(x.:o: , x.x:<\ 
::;,:.xz , X.XXi 
·<xx 
xx.x%) 
(x.xx , x.xz) 
 
2COG: ::;; 
 
XXX 
 
x:-:.z'o> 
 
xxz 
 
x;-; .x"o'• 
 
xx:-:: ( xx.x\i·r 
95% ConfiCence :::n-::.e.::val 
SCOG: 2 
95% Confidence :rc::e:c,,al 
(x.xx, x.xx:, 
XXX ( xx.xS' 
(z.xx , x.xx) 
(x.xx , x.xx) 
XXX ( x;-,.x%; 
(x.xx , x.xx:, 
(x.xx , x.x:-:l 
:,;xx 
;-o-:.x·t 
,:x.zx 
;,:.xx) 
 
 
c:;: is 
based or:    Clopper   ?earsor.  S:-:act   l. ..... L 
?rogra::n r.Jar:;e: 
Listing Sou.:::-ce: 
?..epeat ::or t.he followi.ng displays: 
::a-::e  Ger,erated: 
?age x cf y 
Table- '1. 2. 44 S::.;)g.:::-o:.;p  An2lysis-Corq:::osite CR  :TT ?op:.:.2.2-:.ior 


 
 
 
 
 
 
 
Table 14.3.l.l.l 
Overall Swe.rr,.ary of Ad·,-erse Events 
Safe::y ?opu::..ation 
 
::ontrol 
(N = XXX) 
n (%) 
 
Low CX-01 
(N = xxx) 
n (%) 
 
High CX-01 
{N = xxx) 
n (%) 
 
Overall 
{N   = xxx) 
n {%) 
 
 
 
Patients with A:t,y Adverse Eve2ts 'ASs) 
Patients ,-,it!l Any T.::eath,ent-Eme:r-gent 
Adverse Ever:ts (TEAEs) 
Patients with A,,-_}' AE ty r:-:axirm.1.rr, NC::::-CTCAE 
g::.-ade 
 
2 
3 
 
s 
G:::ade 1 or .c:: 
Grade 3 or 4 
Grade 3 or above 
Patients ,,,ith A2yTEAE by axinn. --r:. NCI- 
CTCl-\.E grade 
l 
2 
3 
 
5 
Gradel or 2 
Grade 3 er    4 
Grade 3 or above 
 
 
The derwminator f:::,r percentages is t:.-'.e r:cJ..c,ber cf patients in the Safety Populat.::_or, 
Cases with s.,.r:kr:.owr, severity ,,:e:::-e assLL-r,ed to be severe. 
 
Program l\a:me: 
Listii:1g Source: 
Date   Generated: 
Page of 
x::,:x 
xx.x%} 
XXX 
xx. 
x:-;:x 
:o:.:--· 
;,:x;-1 
xx.x?s) 
xzx 
xx.x'l;) 
XXX 
x:-:.z%} 
XXX 
xx.;-: ' 
;,:;,;·,·  
:,:x.·,-, 
XXX 
XX.X'ii 
XXX 
xx.x%) 
X<'.Z 
xx. xc:,: 
xx.xi) 
xx:,: 
xx.x% 
XXX 
xx.xS '- 
XXX 
XX. z l: 1 
;,:xx 
xz. 
xzx 
xx.x% 
XXX 
xx.x'i: 
XXX 
xx.xS 
;o::•: 
XX.X''.; i 
XXX 
xx.x% 
XXX 
xx.xi·, 
;,:xx 
xz. xli 
:,:xx 
>D'. :-;:%) 
XXX 
xx. 
XXX 
xx.x% 
xxz 
xx.x 
x;,:x 
x x . z 
0 3; 
XXX 
xx.z%' 
XXX 
xx.z't) 
:-:xz 
xx.x'i: 
;,;xx 
xx. y>,) 
XXX 
XX.X·O 
XXX 
xx.xi& 
zzx 
xz. 
;,;}:X 
xx.x 
XXX 
xx.x%" 
XXX 
xx.x:;c 
:<xx 
>'.Z. x'o ·, 
XXX 
xx.x 
XXX 
xx.:s:% 
XXX 
xx.x%, 
;,:xx 
xx.x'c' 
xz.x 
zxx 
xx.:d. 
XXX 
xx.xi·, 
;-:zx 
;,:x. 
:,;x;-c: 
;,:x. X·O i 
XXX 
xx.x% 
XXX 
xx.x½ '- 
XXX 
XY. X·}\ 
x:-:x 
xx. 
xxz ( 
x:-:.z\';) 
;,:xx 
( xx.:--:%) 
XXX 
( ;,:x. 
;,:x.::-: :) 


 
 
 
 
 
 
'Zable "'1.3.l. 
·::::verall S ":W,a:::.-y of Adve::se Events 
Safety Popi..;lation 
 
::antral 
(N = xxx} 
n (%) 
 
Low CX-01 
(N = xxx) 
n (%) 
 
High CX-01 
(N = xxx) 
n {%} 
 
Overall 
(N   = XXX) 
n (%) 
 
 
Patients with A:,•:/ A::":s leading to treatr:-,ent 
 
 
 
 
 
 
 
 
 
 
, 
 
 
 
 
 
 
 
 
 
 
?he     denominator   for   percer..tages  is   the   nu,.--n.ber   of     patier.t.s .;,.r,  the 
S2fety Fopulati.cn 
Cases -:.,·i th unkr,o,.,n seve::ity were assu.7,ed to be severe. 
 
Program Nar:-,e: 
Listing Source: 
Date Ger:.erac.eci.: 
Page 
of y 
inte:-rupti -, 
Patients 
th Ar::y 7E.n.Es leading to 
xzx 
h.•,.f .. 
XXX 
xx.x"o 
XXX xx.x :, 
X}'.X 
xx. xi) 
:.. ec-:..:c,e.. :. ........ c.e _ ,._,p:_.:.o,, 
XXX 
xx.x0, 
XXX 
1/.X. 
XXX xx.x½:, 
XXX 
Y.>:. x's 
Patients w t:-, Any AEs leading -:::o trec.t:.nent 
-eductinn 
XXX 
;-;x.X'2 
XXX 
;,;;-:. >: 
XXX xx.x'i,) 
xx 
xx.x,, 
Patients with;.-,-, 'I'EAEs leading to 
-;-"""a-;-1·"'·". .. "'"""du,-t; ,., 
Patients with F:.n·· .A.Es leading to trea':.rc:ent 
disco:-it.i;.;uatior. 
XXX 
xx:-: 
xx. x:-
s. ,., 
x:-sx 
;-;x;-: 
xx.   x"o i 
xx.   x'i\ 
x:-:x 
xxx 
xx.·,C·'  
(   xx.x%} 
zzx 
xx.x%) 
·-:.%) 
Patier:.ts ·.1i tr: An.,, TE."'.Es leading to 
treatmer.t C.iscontinua-;::ion 
zxx 
xx. 
XXX 
xz. xt; 
:,;;.;:x 
xz.x%) 
;,:;,;;.; 
xv ySc' 
Patients with AnySeve::e Adverse E1;e:;;:.s 
(SAEs) 
XXX 
x x . x 
0 
·· 
XXX 
xx.x';.,) 
xzx 
XX.X \'• 
:-:x:•: 
x:-: 
Patients with Any Treatmen"t-Emergent 
Severe Adverse Ev·ents (TES.fl.Es) 
Patier,_ts •,;i ti Any SAEs leading to dea:.h 
XXX 
x:-:x 
xx  .. ,.).\ 
xx.::s·, 
zxx 
XXX 
XX •.iCC 
:•:x.x'i) 
xzx 
;-:xx 
xx.x%) 
xx.;{:±; 
xzx 
xx. 
XX.X':0) 
Patients •.•:ith A::1y TE:SAEs leading to death 
Pa::ien::s with Any S."\Es 1eading to 
XXX 
xx 
XXX 
xx. x'::) 
:-:xx 
xx.z;•:; 
X}:;-; 
xx.x ,) 
treatment disco:-itinuac:ion 
Pat.ients witr'. .A:-iy TES.AEs leading to 
XXX 
xx.x 
>:x:-: 
xx. 
xzx 
xx.x%) 
XX>-: 
x:--:. :,:?;) 
-;-_y-;:,atment disco:;.tin.1.;at'.io:, 
XXX 
xx.xi' 
zxz 
;.;:;,;._;.;:;) 
XXX 
xx.x 
zxx 
xx.x% 
Patients with any st·Jd)' drug :-elated -"-Es 
XXX 
xx.x%l 
;-:xx 
xx.x'i:) 
XXX 
xx.x 
XXX 
xx.x"t 
?atienc:s with any study drug related TEAEs 
x;,;:s 
xx.x%) 
XXX 
X. ;t) 
XXX 
xx.x 
Y.XX 
xx.x% 


 
 
 
 
 
 
 
Table  ·," 3 
s·c1;JL-r,ary   of     Treatment   related   Ad 0; er  s e    Event    (Idarubici::-i) 
Safety ?cpula-::=ion 
 
:::ontrol 
(N = XXX) 
Low CX-01 
(N = XXX) 
High CX-01 
(N = XXX) 
Overall 
(N = xxx) 
n (%) 
n (%) 
n (%) 
n (%) 
Patients  '. i 
.I:iarubicin re:.ated Adverse 
Ever,ts (AES 
:,:xx 
xx.x%) 
XXX 
xx.x ,) 
zzx
:,: 
;,;':;', 
:x 
xx.:d) 
Patients  wi 
Iciar,ibicin related Treatmer,t-
Err:ergec::: Adverse Ever:ts (TEA:'::s) 
XXX 
Z}:.:-r'"' 
XX'.{ 
:-.:;,:. 
x; x 
zx. -,.·" 
xx.x%) 
Patie::-,ts wifr, Idarubicirl rela':ed A:S by 
Zc,.c.A·½""-'· '·<c.-..L-• ·Ct ::., £'.re.."' 
XXX 
xx. 
xzx 
x:,;. xSc 
XXX 
xx. 
zxx 
zz.z,}) 
2 
XXX 
X};. X"" 
XXX 
:-:x. x> 
XXX 
xx. 
x:-.:x 
:-:x. xi'.; l 
3 
XXX 
xx .. ,.;· 
xx:,: 
x:{ 
XXX 
xx. 
:•: ::{ ( xx. x% l 
4 
XXX 
xx.x% 
:,:x:,: 
·-·,.:{'i;' 
XXX 
x:-:.x'" 
XXX 
xx.xi) 
5 
XXX 
xx.xi' 
;co: 
X:.Z'c, 
:,;xx 
:-:x.x?o 
XXX 
xx.x%) 
Grade 
or 
2 
XXX 
xx.xt; 
XXX 
xx. 
xxz 
Z' 
zxz 
xx.x%) 
G:rade 
3 or 
XXX 
xx.x%"; 
XXX 
xz. x?;' 
XXX 
:-.:x_-,-o"' 
XXX 
zx. 
G:rade 
3 or abcve 
zxx 
xx.xi) 
XXX 
x:,:. x"'· 
XXX 
:,:x.x% \ 
xzx 
xx.x%) 
Patie:1ts wit.h Ici.ar,.;Dicir. rela'.:ed TEA£ b:,/ 
maximu,.L, NCI-C'.:'C"'.E gracie 
xzx 
X}:.x½; 
XXX 
X •:. >:'.!i) 
XXX 
x;,:. x'i: 
xxz 
zx. 
2 
XXX 
xx. x:: 
xxz 
:,;x. 
XXX 
x::,. x'2) 
;,;xx 
xx.x%) 
3 
XXX 
XX. 
xx::-: 
xx.::-:':: 
xxz 
xx.z?' 
xxx 
xx.x'bl 
xxx 
xx.x%' 
XXX 
xx 
XXX 
z 
XXX 
( z:-.:.x";) 
5 
XXX 
XX. X·c 
:u:z 
xx.x 
XXX 
XX .X'" 
;-::o: 
xx.;,;'\) 
Grade 
or 2 
;,:xx 
xx.xt) 
1/.XZ 
x;-.:.x 
XXX 
:::,: . 
XXX 
xz 
Grade 
or 4 
x:,:x 
xx.:-vo' 
XXX 
zz.x 
XXX 
.x:.z 
XXX 
;,:::, . x-3 
Gracie 
or abcv-e 
;,:xx 
xx.x·o' 
xzx 
xx.x 
XXX 
xx.z 
x:-.:x 
XX. x'o 
 
Cases with t.:.Ek::-.01-:n se·,:eri ty were assc.:.-r-.ed to be severe. 
 
I_'rograrrirri_ih_g Not.es:: 
Change, drug na..cH? to, !d2r't:i.bicin related. 
Program Name: 
Listing Source: 
 
 
Date  Gerierated: 
?age x of J 


 
 
 
 
 
 
Tab2.e   14.3. .,_, .  .c. 
Su,,c:t.a:.::y of Treat:.c,er:t related t'.dverse Event (Ida:.::s.,bicir-,) 
Safety  Populatior. 
 
::antral 
(N = xxx) 
n (%) 
 
Low CX-01 
(N = XXX) 
n (%) 
 
High CX-01 
{N = xxx) 
n (%) 
 
Overall 
(N = XXX} 
n (%) 
 
Patients 1s·i th Idarubicin related _;:::s 
leading to   treatmer;t   inte:.::n:.ption 
Patients ;..·i th Idarubicin re2.ated 7E.;:i..::s 
leadir,g c:o treatmer:t inte:.::cJ.ptic:-:. 
Patients ·wi tl": Idarubicin ::::elateci ASs 
leadir,g  to  t:.::eatmer,t   :.::eductior, 
Patients with Idan:.bicin :.::elated 7EA:Ss 
leadir,g   to  treatment r 
ductior:. 
Patients with Idar'.lbic n related _;;_ss 
leading to t:.::eatmer.t d scontinuc.tion 
P2tients ·,,ith :Cdc.rubic r. relc.ted 'I:S;o.Es 
lee.ding to t::::eatment ciiscontinu2tior. 
?atien.ts ,,ri th Idar1;.bicir. ::::e::_ateci Sesrere 
Adverse Events (SAEs) 
?atie1;.ts with Idan;,biciL re2.ated Treatme;;t-
E;:ne:rgent Seve:.::e _;c.,.cerse Events 
{"I'ESAEs) 
Patients ·,,·i th IdaruOicin :.::elated SAF.s 
leading to death 
Patients ;,·i th Idarubicir, relateci. TESAEs 
leading to death 
Patier-,ts with Idarci.bic E rela::ed SAEs 
leading to treat:2ent C scontinuatic-:--, 
Patients ·,,.'c t:r; Idarubic n re:2.2,ted TESAEs 
leadir,g to treatment d scontinuaticr, 
 
Cases ·,-:itf'. \.ln>:no-.-;n severity were assu.c.ed t:o te se'.'ere. 
 
f,rcgi::.a--riroiii.g·- -fbtes: 
Cha:n9'e :-dr·u_g -name to· Idar'v.bi:cin· r lated 
Program Name: 
I..isting Sou:.::ce: 
Repeat for the following displays: 
 
 
Date   Generate::i: 
?. ge x of ,,.- 
>:x:,: 
zz. 
XXX 
-  :>'· 
XXX 
xx.x%) 
zx.Y" 
XXX 
x:.,:. 
XXX 
XX.X''o'i 
XXX 
:-;: -•;: :<'"• 
;.;;-;): 
xx.;,:'i 
xz;,; 
:-;:x. x l 
XXX 
xz. x0 0 
xxz 
zx.x½;, 
XXX 
:-;:x 
x:.,:;--: 
zz.x½ 
x;--:x 
:-:x 
XXX 
xx.;.:'t '. 
x:-:;•: 
:,:.x 
;.-:x;c 
x:-: 
XXX 
XI":.;:-,; 
XXX ( XX.Zf 
xxz 
}: ,:• :;-:'.6; 
z;,:x 
•,:i':) 
XXX 
x;.:. :,;:'o 
XXX 
x:,:.xt. 
XXX 
z:cx ,, 
zzx 
XXX 
x:--:. ';) 
:-;:x:>s 
zx.x%; 
XXX 
xx.x":/ 
XXX 
zz.x'· 
XXX 
zx.x%) 
XXX 
;.:x. 
·,:xx 
;,:x.x%-· 
xzx 
ZZ.Y 
XXX 
xz. 
XXX 
zx.xt' 
zzx 
xx.xS:' 
XXX 
ZX. iZ\ '- 
;;xx 
XY.. x?,) 
n.t'.•. 
xx.z%' 
XXX 
xx.x½J 
zxz 
xz.x":·: 
XXX 
xx. 
x:-;:x 
xx.x't. i 
xx;.: 
xx.z 
xzx 
X 
xx,-: 
xx.x':o i 
XXX 
xx.xt' 
XXX 
zx.x'; 


 
 
 
 
 
 
?able  l4.3. 
3 Su,.cunary of T::eat:-cent related Aciverse Eve:1t (Cytarabin.e) Safe'.:y P:::ipulatior-i 
.i".dd: 
No'.:e ':o Prog-rarnmer: Change drug name to Cytarabi::e re:ated 
 
Delete: 
Note to Progra:;ru-:;er: Change drug name to Idari.lbici'1 related 
 
 
Table 14. 3.::.. s,.:rnr::.ary cf Treatment related Adve::se Event {CXOl) Sa::'"e-:: Pcp..:.laticr 
.:'.\.dd: 
Note -::o ?::og-::amrr,er: C:',ange d:::ug name to CXOl relate..., 
 
Delete: 
No.:e -:.c  ?rog:::.-a::rcmer:  Cf::ange  Crug Lame  to Ida::·c1bicir. related 
 
 
Table   14.3. 
5 S·c1.rn,--r:a::y o::: Adve:::se Eve:it Cue to ..:.r:Cerl·, ins disease er o:::te.::: dcC'gs o:: che:r,.icals Safety Po;;mlatio:1 
_::i._ctc: 
1,Jote to Prograrr -r,e.r: Change dx-ug name to Ur,derlyir:g disease or otf::er d::ugs or chemica2.s related 
 
Delete: 
·Jote to P:::-ogram:.--::-ter: Ctange drug ::-iame to Ida:::c:b.'cci.n related 


 
 
 
 
 
 
 
Table  l.4. 3. l. 6 
Qveral:i.. Cmlnts of Aci.ve::se Es;er:ts 
Sa.:"e::y Populaticr, 
 
::antral 
(N = xxx) 
n (%) 
 
Low CX-01 
(N = XXX) 
n (%} 
 
High CX-01 
(N = xxx) 
n {%) 
 
Overall 
(N   = xxx) 
n (%) 
 
 
AES 
x.:-:x 
XXX 
Zc'.X 
zxx 
TE.;;.Es 
xzx 
:o:x 
zxx 
x:o: 
SAEs 
xx:•: 
z:o: 
zz: 
X%Z 
TESAEs 
z:,:x 
XXX 
XXX 
x:-cx 
 
T::::eatment 1'.'e ated AEs 
x;.:x 
XXX 
xz;,: 
x:,:;,: 
T::eatsen re a ed TEAEs 
XXX 
XXX 
x:-:x 
;,::,:x 
Treat:c,ent re ated SAEs 
XXX 
XXX 
xx : 
X C{ 
'T'reatrr,ent re ated TESAEs 
AEs leading to treatrr,ent inter::uptio:-, 
zzx 
XXX 
xx:,: 
xxz 
xzx 
:,::.,::;,: 
EAE 2.ead ng to treat-e1t _-te::::r-pt-o- 
SAEs leading to treat:r,e:st inte::::ruption 
:--:xx 
xzx 
XXX 
XXX 
XXX 
XXX 
XXX 
xzx 
'iESFEs eaoi"'g to tl'."eat-rre-· -te:::::up ,._,_, 
xx:-: 
XX>: 
XXX 
XXY. 
AEs leadir.g to treat:me:it reci. ctior, 
;.-;;,::,: 
xzx 
XXX 
x:,;x 
TE.;;.Es leading to -:reatment rec\'...:ction 
Y.X:-C 
XXX 
XXX 
x:r:x 
SAEs leading to treat;;r,en,:: ::::e'.:: c::ion 
'i'ESAEs 2.eading to treatrr,ent reductic-2 
x;-:x 
:xx 
XXX 
XXX 
:-:xx 
XXX 
)CZX 
AEs leaci.ing ".:.o treat.:2en.t ,-.'it.hd::::a1•:al 
XXX 
:-:xx 
XXX 
XXX 
TEP..Es leading to treatment, ..;::_t:-lcira',,'al 
x;,:z 
:u:x 
xzx 
XXX 
S.½.Es leading to ':::reatrr.er::: wi. thd::::awal 
::--:xx 
XXX 
XXX 
XXX 
TESAEs leading to t.::::eatRent ,,,:i t!"'.dra,,;al 
XXX 
xzx 
XXX 
XXX 
 
Cases w·i th unKnosir, se,,eri ty ·,.;e:ce  assu.,-r,eC. 1:0 be seve::::e. 
Progrc.:m Na;-r,e: 
I.,isting Source: 
Date Ge;:ierated: 
?age x of y 


 
 
 
 
 
 
':'2b:1..e  14.3.l.6 
Ove!."2ll CO-:Jr',tS cf Adverse Events 
S2::':ety Populaticn 
 
::antral 
(N = xxx) 
n {-%) 
 
Low CX-01 
(N = xxx} 
n {%) 
 
High CX-01 
(N = xxx) 
n (-%) 
 
Overall 
{N   = xxx) 
n (%) 
 
 
 
::-·:::eatrr,er.t related AEs leading to tre2t2ent 
inte:::::.-uption 
Trec.tr:ient :::elated TEF>-.Es :eadir::g --.::o 
.,.,,."'2"°""P'"'t ir-t-""..,.rup1-; .,,_ 
T·:ceatr;ier.t related S.f'.Es leadir::g to 
xx·•· 
XXX 
:-:xx 
x:-:x 
xx:,-: 
XXX 
XXX 
treat2ent interruption 
Treatr'.',ent !"elated T S1'.Es 2.eading to 
:,:z:-: 
xxz 
XXX 
treat::-,er,t inte:cruptior: 
'O'.X 
·.;:,:;,: 
xzx 
XXX 
Treat22r,1: 
,,.ed,:c-:-,-'o-,, 
:'re2trr,er.t 
related P,Es leading tc treatment 
related TEAEs leadicg --:.o 
z:,•·· 
zxx 
XXX 
;-o:x 
tre2::rr,e,:t 
Treatc,,enc: 
red:..:ction 
related s.n.Es le2ding to 
:-<;--c:,-: 
xx:-: 
XXX 
XXX 
 ,,.,:,_:oa .,_.,,,,,-,1- 
Treat:;cer,t 
r<>j;;('.7"; ('f' 
related TESF-.Es leading to 
zxx 
XXX 
;,;:,-:x 
treatcc:er,t x-ed-..:ction 
x:•:;,· 
;,:x:·: 
x:-:z 
xzx 
Treat:c.ent related AEs leading to treatment 
.,,,,._;_ c.:,J '='''c.l 
XX:< 
zx:-: 
xx:x 
;::,-:x 
Treatment :::-elated IE.t,,Es l,c?ading to 
c._,._ec '-"'"'n,.,,_;_1,.hC-'-.awal 
Treat2e,.t related SAEs leaciicg to 
X 
XXY 
XXX 
XXX 
t:::-ea.t:.,er,t wit:,ctrawal 
;.; 
XXX 
XXX 
;-;:xx 
T:::eat:mer.t related TESP,Ss leading to 
treatrr,ent ·wit:'.'.drawal 
;:xx 
:-:xx 
xxz 
XXX 
Cases wit:ti unknow::: severity we::::e ass1..uned to 
be severe. 
?rograrr, Name: 
Listing Source: 
::::ate G,.:merated: 
:?age x of Y 


 
 
 
 
 
 
 
Table H.3.l.7 
su..,c:nayy of T:-::Ass 8y ;'Jed.D? S System Qyga:1 Class and Fre:'.:, rred Term 
Sc.fety ?09ulat:ion 
S;/ste::n ():rgar. Class 
C:c.o.'Fc,.rcod '"'''T 
 
::antral 
(N = xxx) 
n (%) 
 
Low CX-01 
(N = XXX) 
n (%) 
 
High CX-01 
(N = xxx) 
n {%) 
 
Overall 
(N   = xxx) 
n {-%) 
 
 
 
 
2:re erred :e:rm 2 
 
xzz 
x:-:.x% 
 
XXX 
xx. x;, 
 
XXX 
:·:x .z 
 
>:xx 
 
xx.x':>1 
P::::-e erred Term 3 
ec:c. 
x:,:x ( xx.xS' 
x;-;:z 
x:-:. 
x:o: 
xx. 
xx:,;: 
xx.x% 
 
System Orga::, Class 
Preferred Term 
P;::eferred Ter:n 
o.::e- -"r• e,· Tern 
.. etc. 
 
x:,:x 
XXX 
;-:xx 
XXX 
 
xx.x 
xx.xi 
xx.x 
0'/; 
xx.x% 
 
x;,;:z 
x:o; 
XXX 
XXX 
 
xx.xS) 
x.:,. x".;) 
x.:,••  xS) 
xY.  xS) 
 
:,:xx 
zxx 
:-;:{;,;: 
zx:-;: 
 
xx. ; ,' 
:G:.;-::'.\ 
x:-::. 
:-:x 
 
:,:xz 
XXX 
XXX 
XXX 
 
 
XX.>' 
:-:x.x% 
:,:x.xo) 
xx.:,;:";\ 
 
 
 
te denominator for pe::ce?Ttages is t:he r,u.,c-ber of patienc:s in t:-,e Safety ?opu.latior, 
Jote:  This table  cor,,tc.ircs  counts  c:f  patien::s.  :£  a   patient  experienced  more   tha:::  0:12   episode  of   an  ad rerse   e7er,t,   the  patient   is   cosmted  only 
or,ce -within a  pre:·erred  ter:::i.  =t a  patient  experienced  :x.o::e  than  one adv·erse  event  ,,;ithin  a  syste:::-:.  organ  class,  the patie,:_t  is  counted  or.ce 
for each prefeyr,=C terr.-, anci once for the sysc.em organ class. 
Progo'.'a::t Na:::te: 
Date Generated: 
Listing Source: 
Repeat for ;:be fo2.lo;;ir,g displays: 
Pc.ge x of 
'I'aO.le 14. 3. l. 9 Sur:1.nar::/ of :1CI-CTCAS G::::ade 3  or higher TE:ASs  by  EedD?..A Systeo;n Crga,, c:.ass and ?refer::::ed Ter,;n Safety Population 
?c.::.ients ,,:ith Ar,y TEAI:, 
XXX 
xx. xi\:, 
>:xz 
XY.X%) 
xzx 
xx. 
Z>:X 
xx.x 
Sys·::em Organ Class 
x:-;:x 
:-:x.X'S 
XXX 
XX.X'o 
:-co: 
xz.x 
xx;: 
xx. 
?re erred Terrr, 
XXX 
xx.x% 
XX}: 
;.-:z.x½ 
xx.x 
XXX 
xx. 


 
 
 
 
 
 
7able 14.3.l.lO 
Delete: 
S;.1..:ccmary of N:::I-CTc.:..::; Grade 2 or lm•.'er TE.l:..Es by l"ledDRA Syste,,"c Organ Class a2d Preferreci Terr:-; Sa::':ety Pcp-c.12.atior 
Footnote: The de:1c:nir1ator for 9erce:1tages is the ;-;,.1J.--::-be;:- of patients in the sa:=ety Population 
Footnote:  Noc:e:  ·::-:.is  table  contains  cm;;r-,ts  of    patier-,ts.   ::::  a   patient 
, ......, e0     o.. '  Y  o;-;ce  witSin  a preferred ::ers. 
a   patient    experienced mor 
cou;;.ted  once  for   each  prefe:-:-red  ter:;,.  ar,d  o,.ce  ::or  t:ie  syster::,  o::::-:;a::i  class. 
exper1.enced more t!-,ar: 02e e;;:,isccie of  ar,  adverse  event,  the  patient  is 
t:'.:ar:: one adverse eve:c.c: wic:hir-, a syste::n orga::-:: class, the patient is 
Table 
. 3..   ll 
Su.,_,1.cw.ry of Treat:nent-?..elated TEP.Es by :,:edDRA System Orgar, c:..ass and Preferreci :e::::- Safet'' ?op;_;_lation 
TaD:e 14.3.l.... I 
Table 14.3 .... l8 
Population 
 
Tab2.e l4.3.l.l9 
Ops.t:;_ac. . o.• 
Delete: 
 
SU:'"'.',rn.ary of TESA-2:s/Serio,_;_s ':'EA.'::s b::i 1:,:ec;::;;:,;, System Orgar. C2.ass ac:d Prefer::::ed '.:-err:, Safet·.· Populatior.  
 
Surr,l;)_ary cf NC!-CTCAE Grace 3 er hi-:;her TSSAE:s/Serio;is TEP-.Es n,, MedD?..l'-. Syster:. C·rgar. Class ar-,d ?:r.eferred  Term Sa:'.:ety S1..-
;.rnmary cf NCI-CTCAE: Grade 2 or l.o;,·e:::: ::::SAEs/Serious ?EA:;;::s by I•ledD?)l.. Sys,:.er:. c,rgan Class and ?refer:::-ed 7e:::-= Safety 
'foot2ote; The Ce::crr,inator for perce,,tages is the r,Uc-rcber c-f patier:ts in tt-.e Sa:'.:e::y ?opulatj_on 
Footnote: t ote: ';:"his table contains cou.nts of patients. ---= a patie2t experier.ceC. nore t:-".a::1 one episode of a,, adverse eve::t, t!"',e patie::::t :;.s 
cou::ted   only   once  ,,,itl",ir,   a preferred  '.::er2. 
a ;;:,atie"-.:  expe:-ie:--:.ced more  thar: cne  a::iverse ever.t ,,·it:-,i::--, 
sys-:::e:n or;ar: c.::.ass, tr.e patient is 
co,.;_ated o:1ce for each ;:,referred ter:c· aI1d ::,;o,ce £or L:.e s_ys-:::erc, organ class. 
 
:able   ''"  3.l.21 
S0...nmary   of    TEA:::s   Lea::iing   tc    =:ea.tr.  c-.,  l<edD A   Syster:-,  Orga,,  Clccss   <rnci.   ?re:'.:er.red   'I"errr,  Safety   Pcpulatior:: 


 
 
 
 
 
 
 
'Iable    4.3,_ 8 
Su.,-:-z.ary of TEJ:l..:Ss by ?referred Terrr, 
Safec:y Pcpula.t.:or, 
 
 
?refer;:-ed '.i:'er:m 
 
:::ontrol 
(N = XXX) 
n (%) 
 
Low CX-01 
(N = xxx) 
n (%) 
 
High CX-01 
(N = xxx) 
n (%) 
 
Overall 
(N    = XXX) 
n (%) 
 
 
 
?at.:ents witt. A:r:y ·_::,:s_;;;:, 
XXX 
xx.x%) 
XXX 
xx.x ,-- 
XXX 
xx.x".s) 
x;-:z 
xx.x?,) 
?referred :er:n 
XXX 
;,:x.;-:(;·: 
XXX 
xx.x:S} 
;-:xx 
xx.x?;) 
XXX 
XX.X''.i 
Preferred .!:er;:n 
:o:x 
xx.x%) 
x:-::--; 
( :--::-:.x - 
x;c: 
xx x'oi 
XXX 
x:-:.x", 
;:,..-e ,,,,._"'d ,•.c,..-- 
XXX 
xx.x%) 
zxx 
XX.X°'' 
:-:xx 
ZY. x'i;c) 
xx;-: 
x:s.x{; 
?re erred '!'err:-, 
XXX 
x: . x%) 
x:-:x 
xx. 
XX.X'S) 
xx:-: 
x:-:.x%) 
Pre erred 1er- 5 
xxx 
( xx.x%) 
XXX 
:-ex. 
xx.:-:%) 
XXX 
xx.:--:%) 
Pre err:ed ?er::, 6 
XXX 
xx. xs ) 
zxx 
:.:x.:--:<:' 
XXX 
xx.x'.3) 
XXX 
zx. 
Prefer::::-ed Ter::-, 
e-:c. 
;,:;-:x 
xx.xi) 
XXX 
xx.x"o) 
:·:x;: 
xx.x%) 
XXX 
zx.zt,) 
 
 
 
The  Cenc,dn.ator    for    pe::.-centages   is    the    :r:u..,J::er of     patients 
-c.:-',e Safe-::y Popc.Jlatior: 
l ote: This ,:able  co,.ta.ins  co·.mts  of.pa::iem:s.  If  a  patient  ezperi.er,ceci :ncre  -.:I',a;:;  one  episode  of  an  adv-erse  event,  the  patient  is  courcted  only 
once within c. pre:Z:erred t'erm. 
?rogra,r,   ;"ame: 
, 
  .-,3-!-;7g s :ir e- 
 
 
 
 
 
 
\"'----'- 
 
 
\(; 
c 
I 'l-7- 
Date··--Ger:er-a -::,ed: 
?age 
of 


 
 
 
 
 
 
 
?able 14.3.l.12 
'°'oo-rt,rr,ary o= ?EAEs by Relationship tc Study Treatment by :"iedD?.P... Systerr, Crgar, ::lass ar.d Preferred Term 
Safety· Population 
 
System Organ Class 
Preferred Te= 
Relationship to Study Drug 
 
::antral 
(N = XXX) 
n (%) 
 
Low CX-01 
(N = xxx) 
n (%) 
 
High CX-01 
(N = xxx) 
n (%) 
 
Overall 
(N    = XXX) 
n (%) 
 
?atients with J:...ny T:::AE 
Idarubicin related 
;.:;,;x 
;,;xx 
xx.z"s 
xx.xS 
XXX 
XXX 
xx.x 
xx.x 
zxx 
xx;,: 
xx. ;-d;: 
xx.x'i 
xz;.; 
XXX 
;s:x.x%) 
xx. 
Cytarab ne relac:ed 
XXX 
z'i 
XXX 
xx.x 
:•:;,:;,( 
xz.x'· 
;,:xx 
XY .X's) 
CXOl re ated 
;,:xx 
xx.;,:% 
XXX 
xx.x 
XXX 
xx. 
:•:xx 
;•:x. ;s::;,) 
Underly ::i.g disea.se o:: cthe::::- 
ci.ru;s or 
;,:xx 
xx.x's 
XXX 
xx 
:•:.:cs: 
XY  .x'i,•, 
XXX 
x:-:.x%) 
chemicals related 
Not Related 
xx:.: 
x;--::.z:;,· 
XXX 
x:s. x o) 
XXX 
;,;;-,:. 
xx;, 
zx . .:•·'·' 
System Organ  Cl ss l 
xx:<'. 
X:{. Y'"" 
xzx 
xx.x%) 
;,::--:;( 
zx. 
x;,:. x':;' 
Idarubicin re ated 
XXX 
xx.xii 
xzx 
xx.:,:\'.' 
XXX 
;{;,;. x'c 
:-,::{;< 
>:. x ,) 
Cyta:cabine re ac.ed 
XXX 
xx.xS:i 
XXX 
xx.x% '- 
XXX 
zx. x0 0· : 
;-::-,:x 
xz.x'o) 
CXOl releted 
>:XX 
xx.x·s 
XXX 
xx.x'i'-) 
x:xx 
zx.x·3' 
XXX 
xx. x , 
Onderl ir.g disease or ether 0.n.::gs c:c 
XXX 
xx.x"> 
xzx 
xz.x;) 
xx;.: 
xx.x"'.-: 
·,:x:•: 
;,;x.x'i:) 
cherr,ical related 
NotRe ated 
X/'.X 
xx . .,.;,., 
XXX 
xx.;,:;;;) 
x;--:x 
xz. 
XXX 
xx. :.-:"t) 
Preferred TerE l 
XZ:-' 
;{X.Z'C 
XXX 
xx.x%) 
xx;,: 
xx. 
:·:x.;s: 
Idarubicir, related 
x:-cx 
xt) 
;.:xx ( xx.x% 
;:;-,:x 
x;-,. ;.:" ' 
x:, 
:..:x.x%'. 
Cytarabine related 
x; X 
XX.X':S' 
X)SX 
XX. x';; 
zxx 
xx.x - 
xx;,: 
:,-:x.x 
CXDl related 
XXX 
xx.x":o} 
;,:xx ( xx. xS: 
XXX 
;,:x.x';,,; 
xx.x 
Ur.derlying diseese o.:: other dn.-:gs 
or 
xxx ( xx.x"c' 
xzx 
( zx.x% 
x 
xx.x%,; 
XXX 
xx.x 
chemica.:s related 
Not ?.elated 
xx:s: 
xx.xc:,·, 
XXX 
:s:x.x%) 
x.:s:x 
xx.x :: 
XXX 
xx. x%-) 
etc 
XXX 
xx.:--:'c\ 
XXX 
xx.x%) 
;,:xx 
:-:x.xs; 
xx.x%; 
 
The der.ominator for pe:-centages is the :::.L,Tu)er of pat.ie2ts in t:1.e Safety ?op,.-,latiori 
 
Note:   This  table  contair,s  cou:ats o:: pati,,,nc:s. 
2.  patier:t e:-:perienced  more  '.:.l°',c.n  one    episode cf a  7-;;:_n_s,  the 
patier,t is CO"..lnted cnly once .,.,ithi:;1 a 
preferred te::JT, a:c.d o::ce for c:he system organ class. 
?rogra:n  Na:r'.e: 
Dete Ger;.erated: 
Listing Source: 
:2age x of 


 
 
 
 
 
 
 
Table  :C.4.3.1.13 
SUc.v:-cr.ary of TEA:Ss ;:,.,; :·,Jaxi .,..:..,, IiCI-C':'CAE Severity, System Oz:-gan Class and Preferred :e::::::\ 
Safety  ?opul2-::::ion 
 
Syster::, Crg2:1 Class 
?refer::eci Te:::-m 
l,C-'-.:.*'-''" .:O ,,e.,..:.c..j 
 
::ontrol 
(N = XXX) 
n (%) 
 
Low CX-01 
(N = xxx) 
n (%) 
 
High CX-01 
(N = xxx) 
n (%) 
 
Overall 
{N   = xxx) 
n (%) 
 
 
 
?atient.s w:'..t.h Any TEAE 
Overall 
 
XXX 
XXX 
 
:.;z.·.··  
zxx 
XY.. x':',' 
x:,:. X 
XXX 
XXX 
 
xx. x%'. 
xx.xS 
:-:xx 
:,:x 
 
X)'. x> ) 
:,:x.;,:'.5) 
l 
x:,:z 
x:--:x 
zx.::--:'·' 
X>' .xi' 
zzx 
xzx 
xx. .x'<;·, 
zx.  x%1 
XXX 
:s:xx 
xx.zo.:, 
xx.x%:· 
XXX 
xx. x':c 
;.;;-:. 
3 
4 
s 
Syst.ecc, C::::gan Class l 
Overall 
xx.x 
XXX 
XXX 
 
XXX 
XXX 
xz;t 
:{x.:r 
XX.X" 
;.;;{. 
 
zx.z 
:-:x.:,·" 
xx. 
zxx 
zx;-:: 
xxz 
 
xx:•: 
zxx 
.:-:xx 
xx. 
ZZ.   X'':) 
x:-:. x'c) 
 
 
X/:. 
xx :{-\ 
>:xx 
XXX 
:-:xx 
 
XXX 
:-:xx ( 
:-:xx 
xx.x'2 
xx.;,:% 
zx.x% 
 
xx.x' ·, 
x%) 
x;.·.x'o 
:c-:z 
XXX 
xzx 
 
x:.;:,; 
XXX 
XXX 
:•:x.x"1;) 
xx. x':c 
xx.    x: -, 
 
zx. x'i' 
xx. 
}   .. '- 
2 XXX 
3 XXX 
4 
x:.;x 
:s:x. ·,'C \ 
xx.x'c' 
ZX.Z'°c\ 
XXX 
XX.X 
XXX 
XX.  Z 
xzx 
xx.x 
XXX 
xx.xS;, 
XXX 
;o:.x ; 
XXX 
x;,:. 
zx: 
x:-:x 
:-:xx 
:-:x  );i;- 
xx. x% 
xx.x% 
s 
?.referred Tercc, 
XXX 
 
XXX 
 
 
xx. 
;.::xx 
 
x:-o, 
XY 
 
::o:.x 
;.;xx 
 
XXX 
xx.x½) 
 
xx..x%) 
:-:xx 
 
XXX 
x:-:. x?,;. 
 
xx.x 
o,rerall 
XXX ( x;.;. ;.;-l 
xx;{ 
xx.:-: 
XXX 
( :{X. ;.:\; ;, 
:,:xx 
X}:. Z 
XXX 
2 XXX 
3 XXX 
'5 
:-::x.x 
>D•:.x'±' 
XX.X'': 
:,:xx 
XXX 
XXX 
XX.Y 
xx.x%' 
z:x. x-' ' 
XXX 
XXX 
XXX 
XZ.   X'.-i 
xx.x'S 
xx.x% 
:oz:-: 
XXX 
xx.:-: 
xz.x 
; z. X 
XX.X 5 
etc 
xxz 
 
;-:z.:,:·· -., 
 
x;-:x 
 
xz. z·'0: 
 
XXX 
xx.x%1 
xx:,: 
 
/;x.z ;) 
 
 
':'he denc::-,in2::or fo:::- percentages is the nur:sber o=:. patients in the Safety Popc.:lation 
Ncte: Patients with :r,issir:g "1axi:r,u.Te. se-.cerity are co,.mted in L;.e Jve:::-212- category only. l = t-:rild, 2 = ;:,Joderate, 3 = Severe, 4 = Life Threatening, 
5 = Dea".:!",. 
Note: This   table  contains  counts of patients. 
a pa-::::.ent e:-:perienceC more th2:1 or.e episode  of  ar, adverse  evenc.,  ;:h.e  patient  is  cm.:nted  o:1ly· 
once witLi.n a preferred tern and for ::he episode ,1:.::h ::he r:.a:,:ionc:.c--n seve:::-i::y. If a patient e:<perienced more ::han  one  acive:::-se  eve:1t  witi'.in  a 
system organ class, the patient is counted or,ce fo::.· each preferred term ar,d or.ce for the sys ten erg a;,, cl.ass. 
 
?rog:::-am N'ame: 
Date GeD.era"'c.ed: 
Lis::ing Source: 
?.epeat for the fellowing displays: 
 
?a,;e 
of 
XXX 
xx. 
XXX 
xx. x",' 
XXX 
x:·:.x', 
zxx 
xx.x'.'; 
XXX 
:-:x. 
xzx 
xx.xS, 
XXX 
xx.x% 
xx:,: 
z;.:. Z'Si 


 
 
 
 
 
 
Tab:..e 14.3.1.::_.:; 
Acid: 
SLl..'Tu.--::-,a:cy of Treatme::.t-?.elated TEF>,Es by  ;:,;aximw,, I c:::-CTCAE Seve:city, Syster:"c O:cgan c::_ass ar,d ?refe:cred Term Safety Popc:.lation 
Note to ?.::::og:carr:!T,e:::: Replace TEAE  by T:::-eatne;:i.t-Related TEAE 


 
 
 
 
 
 
 
Table ::.4.3.1.15 
,_,_Tu":',ar)" o=: ?EAEs Ca,;.siTJ.g Uiscoc,tinuation frorr, S-;:udy Treatrrten.t Dy CTCF-.E and ,rnrst C CAE grade 
Safety  Pop·c1laticr:. 
 
c::CAE ca tegor""y 
:-JC: CTCP.i'.; t:ere<, 
::ontrol 
Low CX-01 
High CX-01 
()-,1erall 
(alphabetical order) 
'a2-p::abetica.l 
T,..,,..."-.,.. C7 C;:,::, 
(N = xxx) 
{N = xxx) 
(N = xxx) 
(N = xxx) 
a c,s,.- ,,..; t-1-,; ,-, 
C?CA:S category:, 
grade 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
Nu.-:tber i>.;) of subjects 
 
A2-l C'I·CA:C:: categories 
Any 
 
 
 
 
'--  '--A   Cc•- go... y 
P-.n.y 
 
Gracie 
. ·::a.,., 
Gracie 3 
Grade 
Gracie 
 
Grade 
 
x:o: 
XXX 
XXX 
x:<x 
x:, 
 
;,c,:x 
 
xx. x'i i 
x-:.x 
xx.x ; 
zx .x 
;.-:x 
 
x;,:. x%) 
 
XXX 
XXX 
xx;-: 
XXX 
XXX 
 
XXX 
 
xx. 
:s:x. 
;,:x.x',· 
xz. ·, 0, 
;,:z. 
 
xz . ;-;
0
 
 
 
;,;x;.: 
zxx 
XXX 
XXX 
xx;,: 
 
XXX 
 
 
zx 
xx.:··"·' 
xx.x'<S \ 
.:,d 
 
:zx. 
 
 
XXX 
·,:zx 
xxz 
XXX 
:{XX 
C{ZX 
 
x:,s.z,;; 
xx.x\' 
XX.X'i 
xx. :,s(: 
zx.x's 
 
xx. 
 
 
 
 
 
 
 
 
 
 
The deno:r.ir.a.toY foY percentages is the nu.,.Llber cf patier,ts in the Safety ?opc:laticn 
::ote: Tt.is table contains counts c:f patients. If a pa-;:ient experienced r:.\Orf, than one episode 0f an adverse ever:t, the patient is coc:r,ted onl. 
once   within   a  prefel'.red   ter:r,. 
a  patient   expel'.ie::ced  r:corF>   than   one a.dverse   event   within   a  syste:r,  ol'.gan   c2-ass,    t 1e   patient   is   cc0.in t e d   cnce 
for each preferred ter::I acci. once for the systeB orgar: class. 
?rograr:: ?::a;-:-,e: 
Listing S01..:rce: 
D2t:e Generated: 
?age z of 
· 
"' 
Grade 
Gra6e 3 
XXX 
x:o: 
Y.X. 
Y.X. 
:•:xx 
XXX 
;-n:. 
xz.x,,·, 
;,:zx 
XXX 
xx.x-s' 
xx.x :) 
xxz 
;,:zx 
XY .xf;) 
x:s:.x{,' 
Gl'.aC.e 4 
XXX 
zx. ;,·>· - 
XXX 
xx.x".:, 
xxz 
zx. ·.·'  
;-:zz 
xx. x\'i' 
Grade 5 
zxx 
xx. x'c; 
xx;-;: 
u;,,. x', 
XXX 
z:,:.Y 
xx.x-:, 
c·,\...i.-;,..· CAE ...err:-,.. 
Gra6e 
x;-::x 
xx.;,; 
XXX 
xx.•.,::, 
XXX 
;,-:x. x::; 
:,:zx 
C;l'.aCe 
XXX 
xx.x 
XXX 
xx.x 
XXX 
xx.x' ) 
XXX 
xx.xi; 
Gracie 3 
:-:xx 
x;,:.x 
XXX 
xx.;,-: 
XXX 
xx. 
XXX 
zx.x ;) 
Grace 4 
XXX 
xx. 
XXX 
x_;.:.x 
XXX 
xx.x%) 
xx:<: 
·•·x. xs1 
Z::c.. 
G:rade 5 
XXX 
xx. :-:-Z 1 
XXX 
xx.z"o'. 
XXX 
:n: . :<:0 0  \ 
zx;-: 
;-::;-:. x%1 


8= 
_, 
 
 
 
 
 
 
Table 14.3.l.15 
S,.;."cL-n.ary of TE.D,Es Causing :Jisccntinuatior: frort:  Study  T.reatment  n·.,  CTCAE  and  worst  CTCAE  grade Sc.fet    
?op:..:.la::ion 
 
:ontrol 
(N = xxx) 
n (%) 
 
Low CX-01 
(N = xxx) 
n (%) 
 
High CX-01 
(N = xxx) 
n {%) 
 
Overall 
(N   = xxx) 
n {%) 
 
 
 
?atien::s w'._t:h Any AEs leaciing to treatment 
_;_,,c.s.. _u.p--..:. ,, 
Patient.s ,,;ith Specifie::i TEA:Ss .leading to c:.reat2ent 
_;_nc"'- '--'-t-"'--.:... 
?atie:1ts w.::. th 
Any 
AEs leadin9 tc treatment reduct.::.on 
?atie::ts ,-,ith Specified TEAEs leading to ':.reatrr,en:: 
,.-ed1,;.ct.::.c.: 
?atier-,ts 1-;ith Any AEs leaC:in;; to  treat.me 
a_;_s " _;_.. L.<a L._;_v., 
Patients c-;i th SpecifieC TE.AES leading to treat:nent 
XXX 
XXX 
xzx 
 
xzx 
 
xzx 
 
xx.:-cs' 
 
x:-:. xS', 
xx. x'c' 
 
xx.:-:'" 
 
XX      X'.O i 
XXX 
XXX 
xx;-;: 
XXX 
XXX 
 
 
z:,:. x%' 
 
xx.z':i 
xx.z% 
 
zx.:,%) 
 
xx.x'.i;) 
 
 
XXX 
 
xx:,: 
XXX 
 
:-:xx 
 
XXX 
 
 
zx.   xf,) 
 
xx.x'-5) 
xx. 
 
zx. 
 
XX.X'O 
 
 
x:-:x 
 
 
 
 
 
zx:,: 
 
xz. 
 
;,:x .x%) 
;,:x.x\) 
 
x:,;. x::, J 
 
XX.XS) 
ri.is co:,ti:::.:a ti on 
XXX 
:cs:. x':s': 
xx:,: 
xx.zSJ 
zx:-;: 
xx. 
C,\ 
Z{X 
xz.:·d;) 
Patients -1itD P..ny se,h:cre F-.d·,,erse Svents (SAEs) 
Patients ·,•:ith Speci-::ied ?reat::r:.en:::-i::merge:-i.t Severe 
Adverse Events (TESAEs} 
Patier:ts 
'- 
Any S.AEs leading to death 
XXX 
 
XXX 
XXX 
xx. x -., 
 
X}:. 
x:z. X ; °' 
/:x;,: 
 
XXX 
xx:;.: 
};;:. x'/;) 
 
xx.X's) 
xx. x"o) 
zxx 
 
XXX 
XXX 
i":x. z'S) 
 
xx. 
xx.x0) 
z:-:z 
 
xx:-: 
XXX 
XX. X'o i 
 
xx.x%) 
xx.  x
0s ) 
P-3+-i e'"';--S ..•, :.-o Sp"',-.; -!'-i e...; 7"'$;'.\Sc, 
lead.1:.g to death 
xzx 
z:-: .. ,,,._ 
;.;x. x'h) 
;;xx 
;,:x.x%) 
z;-:z 
X>:. x''.,) 
Patier:ts ,.;.ith P.:1y SAEs leadi:,:; to treat:r,ent 
ciiscor'.!tinuation 
?atiects with Specif.::.ed TSSAEs leading to treatment 
 
xx:<: 
 
xx.x'o\ 
 
xxz 
 
xx. 
 
xx;-: 
 
xx.x0 
 
zxx 
 
zx.x"o) 
dis ontirn.;ation 
%XX 
;--o -: . x  5i 1 
XX)'. 
x:,;.xS' 
:;.:x;z 
xx.x': 
XXX 
:e:x. x%) 
Pat e:-i.ts ·,•:ith 2"-Y study Cn:g related AEs 
xzx 
xx.xi': 
zxx 
xx.xi 
XXX 
xz.x%) 
XXX 
xx.x •'• 
Pat e:-i.ts wit:1 any study Cr g :::-elated specified TEAEs 
x:-;:x 
xx. x 0    • 
xzx 
xx.x-\::\ 
XXX 
x;.:.x%) 
z,:x 
xz.x%] 
 
The der:.orr,::.r:.at:Jr fa;:: per:-centages is t:-.e nuw.ber cf pat.i.ec,ts ir:. the Safety ?opulaticn 
<cte;   This   table  contains   20:..::.::its  of     patients,   If  a patie:ct  experienced  :w.ore   than one episode 
an    adverse  eve:1t,   t'.ce   pati-2:r:t   .::_s    counted  only 
o:r:ce  ·,;i thin  a p:::eferreC ".::erm. 
a  patie'1t  experienced  ::.ore   t:?.ar:.   or,e   ad·,re:::se   ev·er:.t   •,;it:,in  a  system  organ  class,  the patient  is  coc:.:-,ted   once 
for each preferred ter::., a:i.C. or:.ce for the sys terr, organ class. 
Prog::a:s 1\ar:-,e: 
Listing Source: 
Repeat for the follo,,•ing displays; 
Date  Generated: 
Page z of 
Table :4.3. 16 
_ op-.,:a c. .... on 
Su.--:i.mary of TreatE",ent-Related TSAEs Causing Disco:,-;::inuat.i.on frorr-, St,.;.dy T:::-eatmer.t Dy CTCAE and wc.::-st C?CAE g.cade Safe-:::y 


µ
•
•
•
µ
 
 
 
 
 
 
 
 
 
 
0 
0 
r,•l, 
0 
0, 
 
µ 
"' 
w 
V• 
•
0 
0 
 
 
 
 
 
jJ 
0" 
V• 
r•l 
m• 
,', 
•a 
0• 
M 
H 
"0 ' 
 
 
 
 
 
 
 
0 
N 
rl 
 
r•l 
,
Q•, 
.


n
 
 
 
 
 
 
 
 
 
>, 
"0 ' 
"o', 
O", ' 
 
 
 
 
 
ct,: 
>..; 
Cl:,-, 
 
 
 
 
 
,",' 
C"l' 
 
 
 
 
 
0:, 
0,:: 
c"; ' 
 
 
 
 
 
"U' 
Ul 
C 
,-! 
·,1 
t'l 
"' 
(IJ 
t,1 r.; 
0r" >, 
f ) ]] ·r1 
El,-< rti m 


 
 
 
 
 
 
 
Table l .3.2.2.l 
SG.'\Ena::::; of Labore.to.::·,,- Test Results and Change f:::o:r, Baseline by Visit-3one Marro,..: 
Safety Populatior, 
3,-,,,-:y   Vi "i   c- 
ccr.t:::ol 
""XXX) 
 
Lo·..,· CX -01 
= ;,:xx) 
 
:iigh CX-Ol 
'}J = x;{x: 
 
Ove:::all 
:-:xx1 
{ %) 
n 
n 
 
3aseli'.1<2 
KXX 
XXX 
x;,:x 
XXX 
 
 
v-· VY 
 
 
 
 
 
 
 
 
 
m.1.n 
 
 
X '..X 
 
xx.:-: 
 
;-:x. ;.: 
xx.x:-: 
c2ax 
.x 
xx.x 
:o:.;z 
XX.XY. 
 
[C6ntinti'e fOr;'-rE!maining post-baseline time poin.tS] 
 
:'iote: For cha::-.ge £:::or:i :Jaselice cal,::ulatio2s, this tables 0,.1,, preser,ts :::esults fo:::  9atiects  with  non-::;-.iss:.ng  data  2t  ;:)aseli:1e  a::1ci time  po.:nt  of 
interest 
?rogram Name: 
Listiu.g Source: 
Date Generateci: 
Page  x of 
:mean (s.d.) 
median 
:;:iin 
:nax 
;,o:.x 
½X.X 
:<X. X 
xx.x 
xx.xx) 
xx.x ( xx.xx'. 
zx. -.· 
x:, .z 
XZ. X 
·:-:.xx 
xx.z 
.:-:z .x 
( xx.;.:;s:) 
xx.;,:z 
xx.z;.: 
xx.xx 
x:·:.xx) 
< Ji sit> 
r: 
:-:xx 
;,:xx 
xzz 
;.:zx 
:71.earr (s.c:.: 
;-::-:.x 
x;-:. xx:, 
xx.x ( xx.x:{·, 
xx.xx 
xx. xx', 
xx.xx 
xx.xx) 
cnediar:. 
X•:. X 
X 
;,:x.z 
:,:x. 
;:n1..n 
x;,:.>-: 
x:-:.x 
xx.;.: 
xx.xx 
max 
:,:x.x 
xx.x 
xx. 
x;s.;,o: 
Change £:::o:r, 3aselir,e 
rr 
xx;.: 
;,::o:. 
XXX 
;.:xx 
mean (s.d.) 
:,:z.z 
xx.xx) 
xx.x ( xx.xx) 
xx.x:,: 
xx..,. 
YY Y"  
xx.:-::-:) 
median 
;,:z.x 
xx.x 
xx.x 
:-ex.xx 


 
 
 
 
 
 
Table 14.3.2.2.l 
S:Z'etary of LaDoc:atory Test Resc:.lts ar,d Change frorrc Baseline by \'isit-3one Mar:cow 
Safety   Pc p 0.:.l  a t  i or, 
Study Visit 
:ontrol 
(N = xx::..;:. 
 
Low CX-01 
(N = XXX) 
 
High CX-02. 
,::_,: = xx:,,·, 
n ('!; 1 
 
Over.3.ll 
xx;{} 
 
 
 
<\'isi c.> 
Auer rods 
l'.J 
,::,:x 
XXX 
XXX 
:,::o: 
Yes 
>:x:-: 
XY.X 
xx.x'.s' 
XXX 
:c:.x%) 
x;-:;, 
xx.:,· 
:-le 
;{;"'.x 
Y.X. 
XXX 
xx.x% 
XXX 
;-cx.x'"\ 
:s:x:-:: 
xx.x'':) 
Response 
Y.:•:X 
XXX 
XXX 
x;,:x 
Mo::::-phologi:::: corr.plete rerr,issicr, (C?.) 
Y.:<:x 
XX.Y.0' 
XXX 
XX.X'c' 
XXX ( ZX. 
·•:xx 
xx.x%; 
Co::!:tplete   re:nis2ion   without   reco-0,er y  o-f 
platelets (CRp;, 
Complete :::-ecTLission withct:.t ne,.;::::::-ophi2.s 
XY.X 
xx. 
XXX 
\ XX.X 
XXX 
XX. :-:7c ) 
XY.x}0    ) 
and/or platelets rc?i) 
'{XX 
;,:x. x't' 
:{XX 
xx.x 
XY.Z 
x:•: 
X>:z 
xx.x% 
?a::tial emissio:1 {?R) 
s:xx 
xx. 
xzx 
);x.x 
xx;-: 
xx.x , 
'.C{X 
z:-:. x';- 
Progress ve dis as (PD) 
:<:XX 
7.X. Xi;: 
xzx 
xx.x 
XXX 
xx.."'.'/, 
;-.:xz 
Stable D sease SD 
:,:;--:x 
.,.. . : 'c 
XXX 
xx.x 
XXX 
xx.z% 
XXX 
xx.;-.:% 
Relapse c:crr, C?. C?. /PR 
,::s:x 
>:x. x'c 
x;-.:x 
XX.X'O 
XXX 
xx.x?i 
zx:,: 
xx.x':,: 
In.deter;:n !:ate 
,:xx 
X :.x:;,• 
:-:xx 
xx.x\"o) 
XXX 
xx 
x;-.:. 
U:iknown 
,:zx 
xx.xo;;; 
:s:xx 
xx.x%) 
XXX 
xx.x% 
:,:xx 
zx.x%" 
[C6nti'nile·. £Or r·emaiii.ihg post-:'ba·s·e1"i -ne tim·e- -pointsj_ 
 
:,;ote: Io::: char:ge frorr, baseline calculations, -chis tables o::-,l·-· p:::esents :ces;,;.lts for patients ;.:ith non-r:--,issl.:1g  data at  baseline a.r"d  t:i.me  point  of  
interest 
?ro·;::aon :-lane: 
7.'5.,.-;,-,-:_:- s " C"'" 
Date  Ger,e::a.tei: 
?age x of 


 
 
 
 
 
 
 
Table  '4 3.2.2.2 
Su.'1lc;a:r:::-' of Labo:rato::::-y Tes:: Results and CI"",ange ::':::::-:r:. Baseline by Vis.::._t.-:-ie:;r,.atology wi::h CBC 
Safety ?cpulation 
Hematology -;..;-i t.:l CBC:  f.err:ogl.obir,  ,: u:-ii t) 
 
 
Study Visit 
:ont:col 
{N = x;•:x) 
LO\•! C, - V - 
xxxl 
:.::, g'"' r·x-n: 
(1-, = XXX) 
Ove::::-all 
'.l.( = XXX) 
n  (%) 
r, 
C, 
 
Baseline 
n 
,.,,.:,.       ,..,              :   C, 
 
'<ed.::_ar, 
Dl:1 
r:-,ax 
 
<Visit> 
 
 
n 
r:;ea.n \s .d. 
Dedian  
r::in 
max 
 
 
 
XXX 
xx.x i xx.xx 
xx.x 
xx.x 
xx.x 
 
 
zxx 
xx.x ( x;-:.xx:· 
xx.:-: 
xx.x 
X 
 
 
xz:-: 
xx.xx { xx.xx) 
xx.x 
Z}:.;-.: 
.··,:.x 
 
 
;-:xz 
;-.; ,: . ;-:z 
:,:z.xx 
xx. x;,: 
x:-:.xx 
 
 
 
xz.zz) 
 
C:J.ar:s:;e from :Sase::.ine 
n 
/:xx 
XXX 
XXX 
r:-,ean (s.d.··  
xx.x ( xx.xx) 
xx.x 
x:-:.x:-:} 
xx. 
:,:;-.:. ZX) 
:-:z.zx 
xz.xx) 
:-edia"'.' 
xx.x 
:,:x.x 
x::. X 
:,;:z.xx 
XlTl 
xx.x 
xx. 
};;-.:. z 
:,;:;,:.:-:z 
:::ia;.-: 
x;-.:.x 
xx.x 
:{. ): 
xx.;,o: 
 
t-t::ont:LnUe £or remaining pos_t_--:baSeline time 'poihtSJ 
 
Note: Fe:::- cha;:-;ge :E:corr: baseline calculaticn.s, this ::ables only presents resul::s :::ol:" patier,ts wi::.r".  no,,-r:--.issin:;  data  at  baseline  and tirr,e  point:  of inter:-est 
rOgr -rimi,hg, Notes,: 
Repe-at- fOr each c'oritinuous fab pai:affieter 
Program Name: 
List.ir::g So,._;_rce: 
Repeat fo:c t.:"?.e followc..ng displays: 
Date   Generated: 
Page x of Y 
Table  14.3.2.2.3 
su..,1Iriery of ::.aboratcry Test Results and Change fron, Baseli:1e by Visit-Coagulation Safety Population 
 
Table   14.3.2.2. 
S
0..:-,-rm-.ar    y    of 
Laboratory   Tes::   Results   and  Change   from   Ease:cine   by  Visit.-Se:ru!ri.  C'."",emistry   Safety   ?opulatior: 
XXX 
XXX 
XXX 
XXX 
XC{.Z 
xx.x 
xx.x 
xx.x 
XX . :z '. 
xx.x 
xx .... 
xx.x 
xx.x 
XY.XX) 
x:,:.x>c 
xx.x 
xx.x 
:-;;-.:. 
( xx.x;-.:) 
xx.xxj 
x:·: 
xx.x:-: 
;,:;,;.:---· 


 
 
 
 
 
 
 
Table  14.3.2.2.5 
Shift. ?able of :,anoYa o::::: ?est  Results icm.;.nts:,  b:,  : -:::_CTC.".E  g:::::ade:  He"1atology  ,,,ith  CBC 
Safety  ?opulatio:-: 
HeBatology   with CBC: He:r,oglobir, 
Control 
LOK CX-01 
 
High CX-0' 
{N = XXX} 
=  xxz· 
(N = :-:xx) 
\·;'erst Occu::-rence 
  
 
Worst Occc,::::re:-:,::;( 
:·Jo:rst C·cc,1::: -rence 
 
 
Change f.::::oc:-, ,,:erst grace to last grade: 
2 
3 
' 
?J 
N 
3 ' 
0 
-1 
 
-3 
Only o:1e :c.easure,r,er,t e::c .. 
 
 
+2 
XZ}: XXX XXX XXX XXX 
XXZXXX XXX x;u: XZX 
xx_;.: XXX 
XXX 
XXX 
XXX 
ZXX      :co: XXX  XXX 
XXX 
XXX   x:,;;z  zxx     X}:X xzx 
XXX  :n::z  xxz   zzx 
XXX 
}D:X    ;,;xx  XXX      XXX 
XXX 
XX}: XXX XXX ZXY XXZ 
xxz xzz XXX :,;x:,: :-:z;,; 
:-;:;,;_;.: xxx 
xx:-· xx: .. x; ;-: 
x: x xx:,; :-:xx ;,::, x xxx 
:zxx  :-:x:s  zx;,:  z:,:;,:  xxz 
 
X>:x  XXX    XXX    X}::, :,:x:{ 
:-:zx   xx:-.:   xxx    :•:xx ·,;;,:x 
xx:{ x;<z xxx :,:;,:x x :>: 
XXX XXX Z:{x  xx;{  XXX 
XXX XXX };:,:x ;{:-::{ :,;xx 
XXX XXX x:<x XXX XX>: 
xx:< xx:< x:c•: xxx xxz 
 
ZXX XXZ  '.{XX  XXX  XXX 
XXX ;:xx XXX :-:xx X:<:i: 
+3 
XX}: ZXX XXX XXX :SO:X 
XXX 
XXX 
XXX 
}:xz _;.:z;-.: 
·,:xx %X:% x;-::x :-::xx x:-:x 
.Only or,e !1'.easure,:tent etc. 
·-:xx zxx XXX XXX xxz 
x::--:z xzx 
xxz 
xzx }:x 
;,; XX>; XXX XX}; 
XXX 
 
 
 
 
Note: This table p:::ese:1:::s ,,o:::st to last va:Cc;e fro::-:t A?:. ;ia;es, by definitior, Ai'.: is desig:ied to :::ecc:::::d s1nto;,;-ard clinica::. eve:-its, so  im:x::o,;e::ne:1ts  are  
usu:ally not reco:::ded 
tr'£ database, this limi-cation of data is ic;rportar.t for t:'..e i::terp::etatior, of this ::able. 
P,r; /gr'.a,ffimin-g Note-s ! 
Repei:it "for eaCh lab -parameter 
Program Ncne: 
Listing Source: 
Repeat fo:c the foJ.. lowi:1g displays: 
Date Ger,era::ed: 
?age 
of 
Table  14.3. ,2,6 
Table 1 l.3., .2.7 
Shift  Tab:Ce  of  Labora-::o::-y  Tes::  Resc.:.2.ts  (co;,;_nts)  by  NC:  C:TCA-2:   grade:  Coaq,   ;_latic:r,  Safety  ?opulation 
Shif:: 'table of Lr.borator,- Tes:: ?esc:.lts (counts) by NCI_C:TCA2: grade: Ser T Cherr,istry Safety Pop;.,lation 


 
 
 
 
 
 
 
Table '4.3.2.2.8 
Shi£-:: Table of ::.,aborat.ory Tes-:: Resc:lt.s \%) by  NC:  CTCA  -;rrade:  Hema-:::olcgy  ,:it:l  CBC Safe-
:::y  ?opulatior, 
Eematoiogy with CBC.Hemoglobin 
Cor.trol 
,:i,.:, = xx:-:: 
 
I.o·,..,·  0:-01 
(N  =  XXX) 
 
E.igh CX-Gl 
'}) "" XXXj 
Korst 
l'J 
GC(T:     P r c 0   
  
 
3 
4 
N 
C\o::st Occu::-::-RT:CR 
:;-Jors-:::   Occ  0.1.r  -:::enc     e 
2 
3 
4 
2 
3 
4 
 
Cha:1:;e frorr, wo.:::st g.:::acie to lase: grade: 
C 
;-:xx :-:zx xxx zxx xx;,.: 
XXX 
XXX 
XXX 
XXX 
XXX 
XX',: :o:x 
xx:;;: XXX 
XXX 
x;-;x XXZ 
XXX 
XXX 
;::-:z 
XXX 
;-;;,:;.,: :<'.XX 
XXX 
XXX 
·,;x;-: xx;,; ;.,;xx x;.:x xxx 
xx:-: :-::-:;< xx;-· xxx 
;,:;-:x 
XXY 
;o:x x:-:x XXX 
XXX 
x;,::,; xx:{ 
XXX = x;-: }(XX 
-3 
XXX 
XXX 
xx:< XXX 
:•:xx 
xx;{ XXX xzx XXX zxx 
XZ}; ;-:z:-: 
XZX 
XXX 
XXX 
cn.::..y  one  :u.easureZ<1er,::: ec:c . 
XXX         }:XX    XXZ  XXX  XXX 
XXX     XXX     XXX   x;o:  XXX 
ZXX  :<'.:-S::{  XXX 
?:x;-.: XXX 
XXX X:{X XXX xx;-: xzx 
XXX 
xx;,: ;-o:x ;,:;,:x XXX 
:-:xx xx;.-: 
xxz 
XXX 
xxz 
::-o:x XXX 
xx;-.: xx;,.: XXX 
XXX 
:{XX XXX XXX XXX 
zz;.; Xz:,; 
XXX XXX XX:{ 
..:.3 
;.-:;{x 
;.-;;-.:;, x:-:x x:-::,: 
xx:--: xx:--: XXX 
XXX :<:xx 
;o::-; :-:zx 
xx;-.: XXX 
XXX 
. Oii.:..y one 
:c.easurezr.en.t etc. 
XXX XXZ 
XXX ;,.:xx 
xxx 
;-:x:-: :-::-:z ;--:xx ;,:xx 
:-:xx 
XXX 
XXX 
x:,:z 
 
 
 
 
: ote: ihis taCle presents wcrst to last valc,e fro;r, A.S  pages,  by·  definitior>.  AE  is  designed  to  record  ,_;_::tOh'ard  cl.irLi.cal  eve:r.-'.:s,  so  irr,proveu,ents  are 
use.ally not recor"cied ir:: the database, t'."',is limitation of data is irnportar,t for '.:he i::terpreta"'.:.io:: of c.r'.is tabl.e. 
?:to(Jramming-:ii6:tes:: 
R€pE:"a'.t fo_r. -iat:h .lab_ -_pa.tB.rneter,_ % fo.i:'- the denominato'r _is _bi!sed on the··t6tal ·wi"t:bin- .each:-·rBC_tarigle ·cell. 
:'..v-; ca,, t-:a1c,8. 
:Jate Generated: 
Listing Source: 
?..epeat fo:::: the followin; displays: 
?ag-e x cf y 
Table  "L    3. 
9 
Shift   Table   of   Laborato::::·,,  Test  Res'.llts 
t:-y  1:CCI_CTCAE  grade:  Coagulation   Safety  PopcJ.la-:::ior. 
ab::.e 
.3.2.2.10 
Shift  Table   of   Laborato:::::i   Test Resu.: "'.:.s 
by UCI CTCP..E g::::ade: SerGTc Cf',emistyy Sa:::"ety PopcJ.l.abo:: 


 
 
 
 
 
 
 
Table .r.o;.3.2.2.ll 
Shi.ft  Table   cf   Laboratory R<csc:lts   (co'..lnts) 
He.satology with C3C:Her:,oglobi::-: 
Safet'.f· Popu.lc.tion 
 
 
 
Hematology with CBC 
 
Control 
(N   = XXX) 
-----c--N 'BasEelin:e_o_o     _ 
 
Low CX-01 
(N   = xxx) 
-- 
Baseline --- 
;-: 
Aot 
 
 ----
 
 
High CX-01 
(N = xxx) 
Baseline---- 
\J  E Tot 
 
 
<Visit> 
Lo;,· (L; 
xx;-:: 
XXX 
x:,:x 
XZX 
XXX 
xx;,: 
X ::<: 
XXX 
XXX 
:,-:x;-: 
xxz 
;,;:,:x 
Nore.al ( :;,) 
XXX XXX XXX XXX 
xxz 
:-co-: 
x;.;z 
;-:x:-:: 
x;-:x 
L:xz 
xx:-:: 
z:-::x 
Eigh (1'1) 
XXX 
XXX 
XXX 
XXX 
x;-.:x 
;-::x;-.: 
XXX 
;,::xx 
XXX 
x:-::x 
Total ·:Tot) 
:{XX 
XXX 
XXX 
XXX 
XXX 
;-.:;sz 
:-::;-;;-.: 
:,:x;-: 
ZXX 
XXX 
<Visit> 
i,C.-; (l. i 
zxx 
XXX :n:x 
:s:xx 
XXX 
;,:x:,: 
XXX 
XXX 
zx;-:: 
;-:;,;x 
XXX 
\:,.,.,.,,,,, 1 
ZXZ 
zz:X 
XXX 
XXX 
xzx 
;-::zx 
:,:;-::x 
: :-:x 
XXX 
;-::xx 
XXX 
XXX 
Eigh {:-i) 
zx:-:: 
XXX 
XXX 
XXX 
XXX 
:-::xx 
XXX 
xx:-: 
X'.X 
XZX 
XXX 
XXX 
Total ,:rot) 
XXX 
XXX 
XXX 
XXX 
xzx 
:-::xz 
zxx 
:-::xx 
XXX 
XXX 
XXX 
XXX 
<_continue for ·an: \risi ts,> 
 
 
:'late:   ?his  ;:able  or:ly  9Yese:1ts   :results   for  pat.ien.ts   with  !"lon-rr;issing  da;:a   a::  base2.ine a:1'.::,.   the 
tirr:e poir::t o:!: ir::terest. 
FrOgr-a,.--mr,ing - Not.es: 
:R.epeat:):cr. ea'Ch l:ab·-para-n':lt:er 
?rog:::artc Na!T!e: 
Listi::-:.g Soc.:rce: 
Repeat for the following ciisp.1.ays: 
iJate Ger::era.ted: 
?age ::-: of 
Table "4.3.2.2.12 
 
7ab.l.e  14.3.. 2 11 
Shi:'.:t :a;:)le cf Lcaborato:::y ?,esc.lts (counts:,: Co2.gu.latio:c:A::-;_ti-Factor Xa Safet" ?opulati.on 
 
Shift '.ra:Ole of Labo::::ato:::y Results {counts)· Se:::-'""-" C:lemistc,-:Albu,,-r,in Safety Pop:;;_laticn 


 
 
 
 
 
 
 
Table 14.3.2.2.14 
Shi::'t Table of Laborat:cry Resc2lts {%\: H.e:ri.atclcgy ·,;:'._th 23C:rte::-,og2.o:Ci,. 
Safety Population 
 
Control 
(N   = XXX) 
 
Low CX-01 
(N   "" XXX} 
 
High CX-01 
(N"" XXX} 
- - 
Baseline  
_ 
  
Baseline  _ 
---- Baseline  
_ 
Hematology with CBC 
e:: 
Tot 
L 
N 
H 
Tot 
5--: 
Tot 
 
 
<Visit> 
Lo:,: 
X:G: 
:,:x 
XXX 
zx;,: 
x:-::x 
XXX 
XXX 
xz;.: 
:G:x 
xz:-;: 
xxz 
XXX 
Nor-ma 
(Nl 
;.;:,::,; 
XXX 
XZX 
XXX 
XX 
XXX 
XXZ 
XZX 
·,::-::;-;: 
Z/:X 
:-'CXX 
XXX 
Hic;r'. 
rt) 
XXX 
XXX 
XXX 
XXZ 
XXX 
XXX 
XXX 
XXX 
z:-;:;-; 
;,;x;-:: 
zxx 
XXX 
Total (Tot) 
zxx 
x:-:::-: 
/:xx 
;,:x:-: 
XXX 
;,:xx 
xx:-:: 
XXX 
:,::,:z 
xxx 
x: x 
<Visit> 
Lo:,·   \LJ 
XXX 
XXZ 
XZ/: 
XXX 
XXX 
XXX 
XXX 
ZXX 
x:, 
:-:xx 
z:-;:x 
:-::xx 
No::-:rcal (N) 
x;o; 
XXX 
xzx 
XXX 
ZXX 
XXX 
XXX 
;.::,n· 
XXX 
Higr', (:-i;, 
XXX 
x:o: 
XXX 
XXX 
XXX 
XXX 
XZX 
xx:-:: 
;s;:, Z 
XXX 
:s:xx 
XXX 
To-:::al '.Tot) 
;.: ·'.X 
XXX 
XZZ 
XX/''. 
xx:-;: 
xxx 
xxz 
xx:-;: 
XXZ 
XZX 
XXX 
XXX 
<Cont±nue ·,£6.b ··all - Vis'its> 
 
 
:;;oc:e: This table only preser;ts res,ilts ::or patients ;,·it:'. non-:;:.issing data at baseline a:-,d t:-1.e tirr,e poi::-,:: of i;;te;:est. 
Progra,_··nm.i'ng··1 ot.e·s:c. 
R€Pea,t :.Jo,r eaC11: lci.b parameter:, 
Program !:0ame: 
Listing Source: 
?.epeat for the follov,ing ci.isplays: 
for the denoffiin·atcr is based on tliELtOtaJ.: ¼"ithin each -sq,Ji:;;i'.e cell. 
Dat.e Generated: 
 
?age :-::  of 
Y 
'7ab.'...e 'L.3.2.2.15 
Shift <;:·able of Labora.to:::y S.esc:.::. ts 
Coag\..:.lation:J:..nti-Factor Xa Safety Populatior. 
 
?able l .3.. 2.16 
Shift Table of Lal::oratory ?..es;;lts ('i'· · Seruc.I Che:m.istry:Albc1<--::l:i.D sa:::et;/ Pop:.i.latio,, 


A
N
 
 
 
 
 
 
 
Figure 14.3.2.2.LI 
PT/IN? ove;: ;:ir::-,e 
Safety ?opc:la;:ion 
 
 
 
0 
N 
 
co 
I 
"' 
:: 
"ii 
"' 
0 
"' 
co 
0 
 
© 
0 
 
Screening 
1 
2 
3 
4 
5 
6 
7 
Time (Day) 
8 
9 
10 
11 
12 
13 
14 
 
Pc:ogc:am Name: 
Listir:g Source: 
 
epea-:: fol'.: the followi::.g displays: 
 
Date GenerateC: 
Page z of 
etc. 
Ida+ Cyta 
lda + Cyta + lower CX-01 
!da + Cyta + upper CX-Oi 


 
 
 
 
 
 
Figure 14.3.2.2.18 
 
Figure 14.3.2.2.19 
 
Figure· 3.2.2.20 
 
Figure 14.3.2.2.21 
 
Figure 14.3.2.2.22 
APT'.:.' 0'7@r ti:me Safe-::y POF-Jlation 
 
P,nti-factor Xa o·--e,::: -ci:ne Safety Pop,..:lac:io:n 
 
?ibrinogen o·ve::: "'.::i",e Safety Pop, :_laticn D-
di:ne:r ove:::- time Safety Popula-cion 
Platelet coun:: over -::i",e Safety ?opula-::.io:1 


"'!"' 
,:: 
0
,., 
,, 
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,c: 
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'" 
"' 
: " 
:a; 
 
 
 
 
 
 
 
 
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0>, 
u 
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,
-,-,1 
aj 
'O 
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0 
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0 
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;  ' 
-- 
<1j  :< - 
0 
GJ II f 
,5 ;::. 
'.<  X  :<:  :,:  X 
X X X X X 
" 
 
 
 
,--i 
0 
('J [;]  -· 
)'       cf,◊ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
,.-j 
0 .- 
 
 
 
 
:<  :-<',  :<:  :,: :,,; 
X     X     ;,:     ;,:    :,: 
:,: 
 
 
x. 
:<   :<   :< :< 
:,:    X  ;,: 
:<  X  :,,; 
 
 
 
 
 
 
)';   :,:   X   ;,:   ;,: 
X     :V'.    X   X 
X 
G
'       [j   - 
r: 
 
 
 
 
 
 
 
 
 
 
 
Q 
•J 
i-> 
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0,"u,, 
0"' 
 
 
,, 
0     :,: 
0 
P     II 
0 
u08' 
 
 
 
 
r: 
 
 
 
 
 
 
 
 
 
r:: 
0 
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w 
0 
 
o'i' 
X 
 
 
 
 
 
 
 
 
 
 
 
,o 
 
 
 
 
,0, 
QJ 
i-> 
.--1 
:J 
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<(j (/) 
<O    I•' 
QI   ,·I 
1:i 
QJ    lfJ   :,, 
d 
'.> .,-1 
/\ 
-,-! 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
f-1 
·,-j 
1·.: 
 
 
 
 
 
:,,;  :,:  :,: 
X 
:,:  :-;  :,: 
X 
:,: 
 
 
 
 
 
 
 
 
'I " 
·d,-; 
 
:,,: 
 
 
 
 
 
 
 
, 
·,-1 
I 
,"m,' 
0 
u, 
 
 
 
 
 
X 
; X :<: 
:   :    ;,: 
X 
0 
Tl    UJ   ;.·: Tl 
P    QJ   U    O   GJ 
w 
U >, l-, ·,1 P 
0 
r; o -,-1 
w 
w 
m 
-o 
w 
'd 
0u,  
0
 
 
 
0 
'f":1 
0 
4-1  ,-. 
1,   "' 
,
(,
),, 
0,u,, 
C(j    p,    <U  P     {) 
;>, .--j    ,   ·,-1  I 
,--1  .--l    O   \.i  +J 
,.,      (\j   ,,_,   .jJ   (/) 
;J        \,I   U)    Q_/  
1 , r:  QJ  QJ  o; 
V     O     D,   II   V 
0 
0 
"' 
, 
 
,c 
(}\ 
U      d 
j.J ()J 
<l! 
-·    r.: 
f.1  •"rl ' 
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r:::  "H' "C' 
0
'H 
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(_')" 
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0 0 
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>: 
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> 
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u 
r:: 
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,.,.-,j 
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r.: 
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0 
 
r. : 
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0 
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{) r:: 
d  U)  0 
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(I]    ':j 
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b, 
d            - '          r?. 
 
.0     <\l  Q! 
l    .'. 4,;j 
:> (/) 
 
 
j.J 
" 
 
 
 
 
 
 
,--1 :,; ---- ' 
,
-,
i 
W 
II : 
0 ;,-:; 
 
 
 
 
 
c--1 
(_) 
:x: :< 
>: ---, 
gll 
:< '" 
·rl 
r-: 
:1; ;.-,; 
 
 
 
 
,0 
0 •• 
: 
--- 
u ;,..: 
: II 
0 
\:! 
•.:i :z; 
 
 
 
 
 
 
 
 
 
.-o-,  R; ,.-_-
., 
H 
,., II 
,.: 
r.; 
 
 
 
 
 
 
 
 
; : : ; 
X :< :< 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
>(    ,'s 
;; 
 
 
 
 
 
:
X< 
 
 
;,;   ;,:  ;    :-: 
:<   :<   :<  :< 
 
 
 
 
 
 
:•: 
>: 
i RR 
X 
 
 
 
 
 
 
0'u" 
f.d 
 
'H 
0 
0 ,. 
. 
;: :< ; 
 
 
 
 
 
 
0 
 
r: 
·<U  .'C,"-S1    r, 
<11    cl)     ·d 
!:i i:i fi 
"0 ' 
:< 
! lTl 
n
\,I  ,·..-,I 
<U G 
o m 
n, ,.:i 
\j ·.-I 
" 


 
 
 
 
 
 
Table 14.3.3.l 
Su.Tu--nary of 2:COG S-:.:atus at Sc.:::-eening and Vital  Signs  at  Scree?:J.ing  ar,d  Start  o::.  Cc::1solidation  Cyc.:.e 
Safety  ?opulati::Jn 
 
 
CJ 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
::r:.ean (s.d. 
,.,.,,,,d; an  
Tc,in 
IT;2X 
SB? (.:1,;c: g) Consolidation 
:-:xx 
x:-:x 
XXX 
XXX 
::-::cear. ,:s.d.· 
xx.x 
x;-:. XX) 
xx. 
xx.xx} 
xx.zx ( xx.xx) 
xx.xx 
x.xx', 
s.edia-:1 
xz z 
XX,'>' 
xx.x 
xx.xx 
:n.ir, 
XY..X 
x;,z. X 
xx.x 
xx.xx 
:2.ax 
xx.x 
x:-::. 
xx.:-- 
xx.xx 
DBI? (rur:Hg) Co:1solidation cycle) 
n 
xzx 
XXX 
XXX 
XXX 
:nean (s.d. 
:xx.x 
zx.xx) 
xx.x 
xx.x:-:} 
:-:x.xx ( xx.xx) 
X}:.xx ( xx.xx:, 
:median 
xz. :{ 
xx.x 
xx.x 
xx.xx 
min 
xx.x 
xz. 
xx.x 
xx.xx 
max 
:x:x.x 
xx.x 
xx.x 
xx.x:,:: 
 
 
?rograrc, Name: 
:.,is::ing Sou.::-ce: 
Date  Generac:ed: 
Page x of y 
:cr:trcl 
= xxx) 
:,o'.'-' D'.-01 
{l'i = ?:zx: 
..., ! ?, ·• 
High CX-01 
(N   =  XXX} 
E ( ; ) 
Over2ll 
I'.    :s:, 
Weight i/;g} (Ccnsolidatio:-:: cycle} 
C 
:,,ean (s.C..) 
XXX 
x.x 
}:X.XZ} 
XXX 
·-:x. 
xx.xx) 
XXX 
xx.:-:x 
xz.:,;x) 
XXX 
xx.·.- 
;,::;-:. 
median 
17,ln 
c:iax 
Height !er.) Co:csolida-:.:ion cycle) 
xx.x 
}:X.X 
x::-:.x 
xx.x 
""(,:,: 
;-: 
xx.x 
xx. 
xx.:,: 
xx.xx 
xx.xx 
;-:x.x:,:: 
C 
,near, (s.d. 
:,z:- 
XX.}: 
zy .xx1 
}'.Z, V 
xx.xz} 
XXX 
;-;-,; ?X  
xx.xx) 
XXX 
xx.xx 
·.•;,:.:c-::; 
.:c:edian 
'.c'.in 
:max 
Hea.:::--::: ?2.te (beats/min) Cor:solidation 
xx. 
xx.z 
xx.;,• 
xx.z 
x:•:. X 
xx.;-: 
XY.. 
:-:x.x 
xx.:,:: 
xx.:-:x 
xx.xx 
xx.xx 
cycle} 
x::--:x 
x::-:x 
XXX 
XXX 
xx 
xx. 
;,::,:,x 
xx. 
::-:x. xx! 
:-::-:. ;-1 
XX.'>' 
xx. 
xz. 
xx.:-::x} 
xx.xx 
:o:.x 
zx.x 
xx.x 
x;-: XX) 
zx.zx 
x:-::, 
:x.xx 
xx.x: 
·.;-.,. vy  
cycle) 


 
 
 
 
 
 
 
Table l 4. 3. 3 2 
Shi::'t of ECG Re s 0-1l t s 
Safet:y- Population 
 
::antral 
Low CX-01 
High CX-01 
Overall 
{N"" XXX) 
(N"" xxx) 
(N = XXX) 
(N"" xxx) 
n (%) 
n  (%) 
n (%) 
n {%) 
<Visit> 
X} 
XXX 
x:o: 
XXX 
:'rorr. r-,ot clinically signi:'icant 
abno:r;r,al 
res-..,lt at baseline to abr-.ormal and 
clicically sig:1ific2r.t :-es'.llt 
?rorr, abnonr:.al and c:inicai::.y 
signif ca::,t 
res'J t at baseline c;o nc-t clinic2lly 
 
 
 
 
 
XX>! 
 
 
 
 
xx.x%) 
 
 
 
 
x:c-: 
 
 
 
 
XX.X"' 
 
 
 
x:,:x 
 
 
 
 
XX.:{'°'' 
 
 
 
xzx 
 
 
 
;-:z. ;{\;) 
sign ficar:t abnormal :resc.1.l':: 
xx 
xx.x%;, 
x:s:x 
xx.x%) 
x;-:x 
= "o, 
xzz 
x:s.Y"' 
t],:,,...h--,-.,g'°'d 
XXX 
xx.x%) 
XXX 
XX.X·3: 
XXX 
x':c\ 
XXX 
XX.X'2 
<. Rej;:ieat for all ,visits where ECG performed > 
 
Note: N: ?Jormal; ANCS:  A.Dno:rrr,al,  Not C:linica.!.. ·., Significant; f'.CS:  P-..D:,o:-::mal,  Clir,ically Signi:':icant 
Prograo:1 :'1ame: 
Listing Source: 
Date G12nerated: 
?age x of 


 
 
 
 
 
 
 
Lisc:.i:1g  16.2.l 
Subjects Screened 
 
T:reatr.:.ent g:roup: Treatment 
 
Site 
?atier.t/ 
Race 
Sex/A'.ie 
 
Date of 
Info:rrr.ed 
consent 
 
;:,,_;,.,..,,-.,,. Reasor; fo:r 
Scree:-: Fai.'..c.:re 
xx 
xx 
.xx 
 
xxx/M/ 4 5 XXX 
xxx/F/35 
XXX 
xxx/M/25 XXX 
 
D')'-jr_,..:Mv\·vy 
DD:-.JMMYYYY 
DDi'lMM'.:"YYY 
 
Reason 
Reasor: 2 
Reason 
 
 
 
 
 
 
P·r·o9 -ra.'r.ming Nb:te_S: 
Repeat: "for all T-reaL--nent groups: _Sort by Treat_ment ·gr:o_up, ·sfte·. and_pat"ient 
Pro-;:ram Name: 
Listing Sou:rce: 
Date Ge:1e:ra pri· 
?age x of 


 
 
 
 
 
 
 
 
 
 
Treat::ne1;.t group: Treat:;;e;1t 
 
Site 
?atieEt/ 
?.ace 
 
 
 
 
Co:::.pleted 
St;_;_dy 
Lis::ing 16.2.2 
S:.ibject Disposi tic:-. 
 
 
?rimary Reason ::or 
'iiiti:drawal 
 
 
 
 
:ate of Withdrawal 
Day)'.a] 
 
 
 
 
ate of 
ast Dose of 
tudy :'reatmerlt gro-c1p 
Se:,:/Ale 
Dal) {a] 
xx 
xxx/M/ 4 
xx2' 
'- o 
Ree.so., 
C::•Drn,11-:'.YYYY {XX 
DmJMMYYYY ( xx 
X : 
xxx/F/3 
XXX 
:-;o 
Ree.son 2 
O._;l•,i-';t. _·:_ 
,: .;..- 
DDMMM'iYT:'. ( zx 
}:>:X/[•1/2 
XXX 
Yes 
Reasor: 
i::;·D:--1'.•'.1·'.:'"Tl:'" 
( xx 
DDt-!M.MYYY:' (xx 
 
 
 
 
 
[a] 
?,elative to the da·, of r2.ndomizatio:1 
P:r_og·ra."r,ming:.Notes 
R'ep·eat· for. ,all 'f:ceati:ne·nt groups · Sort by T_i:Ji:ci£itte11t·.·gr_oup, site. ind Padent 
"· o_.r-•,· .L--,n.-"': 
Lis ;::ing Source: 
Date Generc.teci: 
?age x of y 


 
 
 
 
 
 
 
Listing lE.2.3 
Sc1bject :reatmer;t Allocation 
 
Random:..zed 
Date cf 
Site 
?atient/Sex/.n.qe Race 
?reatrr-ar,t Grcc1p 
Rand:::mization 
 
xx 
xxz/11/45 
xx;.; 
xz;,-: 
DJ11:"'.:•'.':..':YY 
 
 
 
 
 
 
 
P_ic,g'ra.-n.7"< _il$_-_:N t -- -_: 
-Re,Peat  for   all 
tr-eat.c--nent. roups. Sort'b:':i' site- a'nCl patient 
Progract, Name: 
Listing Source: 
Sate Ge::erated: 
:?age x of y 


 
 
 
 
 
 
 
Listir,g  16.2.4 
?ro"'.::ocol  Deviat:ions 
 
     T:::-eatrr.ent group: Treatmer:t 
Sit:e 
?atie:1t/Sex/Age 
Race 
P.ny 
Protocol 
Deviations? 
 
Date 
;:>ro;:ocol Deviatio::1 
Catego:::-y 
 
Details of ?:::-ctocol 
Deviatio:1s 
 
xe: 
:..;:/M/ 4 S 
xzx 
Yes 
J:)>.'eMcJ;VVVY 
z;-.:xxxz;s:xxxzxxzx; 
x:-:i{XXX:•:xxxxxxxxxx :xx 
 
 
 
 
 
 
 
 
No-::.e; Jevia;:ions were ider,tified a,:d categorized prior 
e:-<:clusio:1 fro:c, 
Prog:r:a,,"nTili_ri.g 0Ncit es : 
:"''cl  da  '-"':..,""s"   lock. 
?ac:ier,t:s   rrcay   ha-ve  may   have   more   than   or,e   Deviatic-:-;   ]..e2.ding   to 
Repea:t..foi all 
.Treatment··tjio.u:ps·. -sort by ,T:rea:tm .nt:.group, site; and· patient 
PYogra;r, l:Jame: 
Date Ger:erat:ed: 
Listing Sou.rce: 
 
Page x of 


"
-' 
 
 
 
 
 
 
 
 
 
>, 
"0 ' 
,i,ll, 
o",' 
 
 
 
 
 
 
 
 
 
 
(J)J;\ 
\ b ) 
: , •,. I. 
C        ' 
• ·rl 
o     H 
d        1) 
D>-d 
>:  H 
·rl     () 
if)       r:: 
·d           () 
,-1     •rl 
";J 
'0r".: 
H 
 
 
 
 
 
 
 
 
,ID, 
("
J  ' 
 
 
 
 
 
 
 
"H 
"
1--'1 
<cJ' 
H 
''"' 
,., 
1--1 
,--; 
H 
ID 
t)', 
er; 
'·: 
u"; ' 
" 
<·' 
,n ,n 
w 
·rl 
P 
<\l 
P, 
r 
<1' r'1 
::;:: r,, 
--.._' 
X X 
X  X 
X  ;<: 
-..-.. ........_ 
,o,; 
•{
r/
l) 
:<
:     
;
X
.:; 


 
 
 
 
 
 
 
Listing 16.2.6 
Excl;_.;_sior. Criteria 
 
 
  Site 
?ac:ie:1t/Sex/AB:e 
?..ace El 
E2 
E3 
:'.-4 
E5 
6 
S7 
£8 
E9 
ElG 
::C:ll 
cl2 
e,13 
El4  El5  El6  El7 :'.-18 
 
 
XY. 
;.:x: h-:/45 
xx 
:xx/ /35 
 
XXX 
Yes 
XXX 
Yes 
 
 
 
 
 
 
 
 
Prcgratmning N0te's: 
Sort- by";_si'te and _patii:=-nt 
F c-,,ha,.c ,,:o",e. 
Listing So'J.rce: 
 
 
Date GenerateC.: 
?age x of y 


 
 
 
 
 
 
 
 
 
 
Treatment g.:::-oup: Treattr:e.,t 
Listing 16.2.7 
Study Pop,;lation 
Site 
Pc.tie:it/ 
Race 
Completed Study 
:T? 
!?? 
So.fet· 
   
Sex/A2:e 
 
 
 
 
 
 
xx 
x;.;x/:-1/45 
XXX 
Yes 
•-'es 
:es 
Yes 
 
 
 
 
 
 
 
Progra;:n Name: 
Listing Sci..;rce: 
P:r(igrarhthing-: Notes:, 
Ss.te Generated: 
?age x of y 
Repeat fOr all Treatment grOup_s Sort by Trea:tmBn:t,-g'i-6Up;, s'ite -'ai1d :patient 
Program  i"arr:.e: 
Date Geuerated: 
Listing Sour:ce: 
 
.22.ge x of Y 


 
 
 
 
 
 
 
Listing 16.2.8 
Demographics and 3aseline Characteris::ics 
 
Treat::',ent grc·c1p: Treat:nent ;_ 
Site 
?atient/Sex/.Age ?ace 
3MI 
3'.fi 
We.-i.gr,,_ 
SSP 
Hea:.::t 
,.,:,-f'.nici ty 
Time 
pJ.;I., 
;.;-:-ese ""'"' 
ECOG 
B.aseli,,r-> 
3aseline 
Cetegory 
:g) 
/:JBP 
Rate 
since F>.2.L 
of     2:-,y 
status 
peri?l":era::. 3one 
!c•'c"' 
(CT:',·; 
{beats 
,?er 
rr,:-:.n i 
c_:._c..,,,.o"'.:."' 
("::'ear) 
r   e l e 0;a :-.t 
,,..-"'ci; a'  
r.; sc ---- ,, 
blas::s 
•;Yes/r.;c' 
Marro:,· 
blasts 
or 
,o:;r7i C"''. 
  
findirnp 
 
 
xx 
:-:xx/M./ 4 S 
x:-:x 
XXX 
x;-:x 
:-:x/:-:;.; 
:-cxh:;s: 
x>: 
XXX 
XXX 
:Je 
r,ovo 
Yes 
:-::-;:-: 
XXX 
xx:-: 
 
 
 
 
 
 
 
 
1?ro9"r&lli"ning _rfo't;,_es· 
Re'peat f6r a:Ll' T.reatmen·t ·groups. Sort by Trecatm':!i:tt: groUp, site am:l.patient 
Prograic, Nar'.'£: 
Lis::ing Source: 
Date Genera"::ed: 
?ege 
of 


 
 
 
 
 
 
 
List:ing 16.2.9 
'."iedical History 
 
?reatment group: Treat,'Tie,-:t 
 
 
Site 
Pac:ient/Sex/."'.fe 
R.a.ce 
Systerr: Orga;:-i Code (SOC)/ 
?:::-eferred ·Terc'7![a] 
Verbati:r, 
Date cf 
Resc:. u:cicn 
 
xx 
xz:,:i'i:-i/ 45 
x:-:x 
z:xxxxxxxxxx;,:xx:--:xx/ 
xx:,.:x:,:xxxxxxxxxxxxx:, 
 
xxxxxxxx;,:xxxz:x:-:: 
JDtfr:t, YY':.."Y. 
 
zxxxxxxx>:xxxxx:s:xx/ 
xxxxxxxxxxxxx,-:xxxxx;,: 
 
xx 
x:-:x 
xx:,: 
tior:e 
:-:xxxxxxxxxxxxxxx 
.  r.-'•-';,J-'-;'-"-';, 
 
 
 
 
[a} HedDRA Dictionary (Versie,, xz.x) ,-;as used :'.:or coding. 
[b] 
Relati7e to t:'"le da::,- ci: rar.dcrc,ization 
'.i?'i.c/gral'l'.niiri'9. Note'.sf 
p_e['eat· for.·.a11 ...-T.ceat:ffier-,t groups.·.SO,.rt; by Treatm:ent-·. -9'.i'6_1ipi. i;:'ite.,:• pa·t i€n_t., SOC and preferred te-tm. 
Prograrr. :-122,e: 
Lis;:ing Source: 
Date Generated: 
?age z of 


,,",, 
C\ 
® 
m ,Q 
jJ , •. , 
n , , 
0 <15 
0., >, - 
'"' 
jJ 1J 
(1) ::1 ,u 
n,,- 
U) () ' 
r(J , 
,--i lY• H 
U .Cl 11 
,, 
u ( :J (l) 
/} t-< 
, ,--1 0 ( T: 
1t1 re; r 
p,.,.1 cl) 
;, (IJ QI 
.c: u 
(l) .c: ') 
l·< 
,,",' 
u, 
·d 
r.: 
d
0"
i.)
ocJ 'm" 
f-ll,,·_d , 
 
 
 
 
 
 
 
 
 
r.; 
--.. 0 
"f  
p       <fl 
 
 
 
 
 
 
'1-1 
.,j 
%' 
0
 
!:·<    ::i 'CJ 
(..1 
 
 
 
 
 
 
 
 
 
 
 
 
 
ITT 
p 
·,-! 
 
,..:.j._ ·, 
>:  :,.; :< 
:-: 
,m, 
,r!, 
'. 
>.: X : 
X X X 
 
 
 
 
 
 
 
 
0 
 
 
 
 
 
 
'cl 
ITT 
p 
aj 
0 
",: 
l"'i 
 
 
 
 
 
 
 
 
 
 
 
Q!   >1 
f': ':i 
qj 
8     UJ 
fd IT 
l ·cl 
 


 
 
 
 
 
 
 
Listing  16.2.ll 
Concorr,i tant ('Jed.ica tion 
 
Treatmer.t <;_!?U_F: Treatxenr: 
 
 
 
 
Site 
?a'.::ie7it/Sex/Age 
Rc.ce 
 
 
 
T::-ie.:-apeutic Class 
Cher::ical Subgroup 
c:2:1;:,r--i c  Term  '.a] 
 
 
 
ose/Dr:i:./ 
.:ut ,.cy/ 
 
 
 
 
 
I,1dicatio:1 
 
Co:rresponding 
ter:n fo:c 
cor,co:nitant 
disease or 
a::5.s;erse e-,,en::: 
 
 
Sc;.;rt Date 
1 day_; 
L lIT,8 
Sto9 Date 
(day/ [bJ 
'.Cime/ 
DuratioH 
  
(da_;[S) 
 
 
xx 
xxx/M/45 
xxxxxzxx:-;:x 
xx/ur,i ts/ 
ANL 
DD:•11-l!·!YYYY 
xxxxxxxxxxxxxx 
xx/ 
(xx) 
1 xxx:-:xxxxzxx:--:l 
xx 
pci•Ml\'1 
o:;11:-;;wyyy 
 
 
 
xx:-;:xxxxxxx 
XXY.X) :,:zXXXXXXX 
(xxxxxxxxxxxx) [cj 
 
 
 
xx/uni:::s/ 
xx/ 
xx 
 
 
 
·J:reat:r,ent o::: 
P.d,,-erse Sver:t 
{xx> 
HB:MM /xx 
 
x:-;:;-: 
DDl/,l-lMYY-'!.Y 
(xx)/ 
001"11-:MYYVY 
(XX) /x>: 
 
xx 
xxx/F/3S 
No:--.e 
 
 
 
 
 
?rogram r:ame: 
Listing S01.:rce: 
Date  Generated: 
Page x cf Y 


 
 
 
 
 
 
 
Listir:g lE.2.12 
?ost Medicaticr, 
 
Treat.rr,er:t group: Treatment 
 
 
 
 
Si-ce 
?atier,t/Sex/Age 
Race 
 
 
 
The::apeutic Class 
C:',esica:C S1.1bgrcup 
G"'·"'"'·"'  r   -""'"'  [:o. 
 
 
 
Dcse/Dr,it/ 
Frequer,cy / 
?..o;.1te 
:n...:.:.c.c ... i..on 
 
Correspcr::di:ig 
ter:::-: for 
, o;,co..- ·  c.2·-- 
dise2se o.::::- 
adv-e.::::-se event 
 
Sta.rt Date 
(day) 
Ti::r,e 
Sc.o:--< Uac.,:; 
:::iay; lD 
'T"irr.e/ 
=:uration 
  
(d2}_'S) 
 
 
x:x: 
x:-:x/ U 45 
XXX 
xxxxxxx:c-:x 
xxxxxx:,:xxxxxxx 
'.xxxxxzxxxx:-:x} 
xx;':,ni ts/ 
xx/ 
x;,: 
.",,ML 
 c--•"'·c"",,, 
'.xz·, 
c.:,.:-I'--11'' 
Drn,;1,; '.YY ;v 
E:i:1·'.M /xx 
xxxxxxxxxx 
XXXXXXXXXXXX}:X 
(zxxxxxxxxxxx) [c] 
xx/ur:its/ 
zx/ 
xx 
Treatment of 
Adverse Event 
X 
O:..,bi•,!.'i r , t 
\;--::-.;) / 
Dc;';l,", i 
-':<::--:) /xz 
xx 
xxx/E'/32- 
•lone 
 
 
 
 
 
a 
WEO ;)rug Dic-::ior,a:cy (Versior. xx) ·,.,as used for codir.g. 
b ?.elative  to  t:'1e   day   o-f   .::::-ando,nization  r
 
grt,u\t.t..i_ni;( _Notes·: 
·.Repeat fer all Ti€:citme_nt groups. Sort by Tr.eatmE:n:t ."gr 6 up 1 s_ite, patient, ·.s·tai:f date:'<Otnd.d.r:u9, clas·s:,  
Progra:n  Name: 
Date Ger:cerater: · 
Listi:ig Source: 
 
 
 
Fage x of 


 
 
 
 
 
 
 
-isi::ing  16. 2.   3 
Stud:i-'  Drug   Gsage   a:1G. 2:zposu:::-e 
 
1reat:rr,ent g:::-oc1p: Treat;£1en+- 
 
Site 
Patient 
 
eye.le 
Initial 
 
Id.arc..:.biciD 
Cyta::::abine 
CXGl 
 
,,.,,,,atsent 
l'J-c.<1.cJ:::er o:t  
;JtL""iUJer of  
N ,cber 
Any Dose 
/Sex/Age 
ez:-Cl 
usage rate 
usage 
rate 
-_;_sage 
Sxpcsu;-:-P 
ra::e 
'.Jays; 
days  on 
days  on 
of 
a.ar _;::,~c~- 
Cytarabine 
da ,s 
0'1 CZ- 
"to,._ :...!;-''--'·ens" 
  
en 
 
xx 
xxx/1•1/ 45 
Ind:.J.ction 
XXX 
XXX 
xzx 
:".:-:::x 
x:,,:x 
:-:::zx 
zxx 
N 
 
 
 
 
 
 
 
 
P:io r-ir&n_ing Not!!:s.: 
Repec.t for all T-ticttmeht _g'rou)?s .. :s·q-_:i:'+,:, ·-oy. _'l',r'e;atm&ri.t -g'±:ouPr-:•:Site· and patient 
2-0,; a:u  lla;r.c;. 
Dae. ,.,e'"""-"-'--e,_;. 
Listing Source: 
 
 
Page x of Y 


 
 
 
 
 
 
 
:Sisting 16.2.14 
Efficacy pa.::::t 
 
TreatBent g;,:-oup: T:::eatment l 
Site 
Patie:-.t 
Race 
Achiev·ed 
Dead? 
?rirr,ary st,,;dy 
Last 
sve:1:: 
Study day 
Leukecnia 
St: ;,dy day 
?,elapse? 
Sts.:.dy day 
/Sex/Age 
C?,? CRi? 
ca...;se 
day of 
study 
T:::-ee? 
to which 
Tree? 
to c,·h.i.c::', 
to K:1ich 
Cor.,pos:i.te 
o-f: 
:R? 
death 
Death 
day  of 
fol lot,·- 
up 
pac:ien:: 
experiewced 
e·Jerct free 
patient 
expor; -"'-,', <:,,..: 
leuke"1ia 
patiecic: 
experier:ced 
relapse 
  
.free 
 
 
xx 
xx;-: /l-1I45 
xxz 
t:/i'i/N 
xx 
XXX 
xx 
xx 
i(X 
xx 
xx 
xx 
xxz 
xzx 
 
 
 
 
 
 
 
tro:9":c'ariimi:r1 r.·1'Tote_S2: 
Repeat for ·a_lJ:. Tieatrhent -;rroups. Sort by Treatn\en'::. -<;rro}.lP -. ,,o.i_te::_and pa,_:ti'e:nt 
Prograr;i. t-::ane: 
Listing Sou:.::-ce: 
Jate Ge:1erated: 
rege z of y 


 
 
 
 
 
 
 
::.,ist::.ng  2.6.2.15 
Efficacy pa:::-t 2 
Treatzr:.er,t gro·c19: Treat:nern:: 
Site 
22::ient 
Race 
p,,--.;-,.;.e,ve,-: 
Dead? 
?rirr,ar:,, 
St:,..;dv 
Last 
Necc.trophil 
S':c1dy day 
?la-:::elec. 
St"..,dy 
/Sex/Age 
CR? CR 
Ccr:',posi te 
C?.? 
ca'-lse o:'. 
de, -:::h 
day of 
sc:i.:.dy 
Geatr', 
day    of 
:Ec-2.lo·.-.:-- 
;.:p 
?.ecovery? 
"'.::o whic:: 
patient 
ex:_::,erienced 
ne trophil 
reco,ser.'i 
Reco-very? 
day to 
whict: 
patient 
platelet 
reccve:::-z 
x;,;x/1•1/45 
:·:xx 
Nit-:/::-; 
:-::x 
xx 
xx 
xx 
xx 
:,:x 
xx 
xx 
 
 
 
 
 
 
 
?r_ogranuni:ri'g Notes-; 
Repeat '.for a.l.l T-l::eatmE'nt· grpUps;:;_ Sod: bj. T,ieatment gr-tiuP site· iind patient 
?rogram Name: 
Lis;:ing Source: 
Date Genera-:::ed: 
?age ;<: of y 


 
 
 
 
 
 
 
 
 
 
 
Treatment g:::ou:e_: Treat.:ne;;t 
List:ir.g 16.2.::_o 
AC:verse s-,,en;::s 
Safety ?opu.latin7 
Site 
?atier::t 
/Sex/Age/ 
?..ace 
SysteccI O:::ga.;,. Class/ 
Preferreci Ter::rJ 
Ver:Oati:7, :2J 
:::c.,;, c. Uccc.e 
Cc 
':'i e 
S,::q:, Date 
(day'- '.b) 
Time/ 
Juratio::c 
c-,,,a -r>.,,n 
E:nergent? 
AE   is    due   to 
:ir::der2-ying 
dc._sease or 
ether drs.1gs? 
Probcble 
Sh,_., , .-1-·,q 
causeci. AS? 
Action 
'Iaker; 
with 
stuciy 
dro..:.g [c; 
Oc:.tcose 
NC! 
SA2 
CTCAE 
Gracie 
  
,:da_ys: 
 
 
xx 
xxx/l•l/45/ 
xx:-: 
xx>:xx:-:x ,::,:;,::zxx:<xxx;.:x 
x:,::;o:xx:•:xx ,:x;::,::xxxx/ 
');-y,,;;,..<'.V:VY·v·v 
(xx'> 
H ;i·/,l•: 
No 
Yes 
Yes, 
"'.' ·-rv·,:c:,. 
XXX 
Re- 
solved 
: o 
.:-:xxxx:,:::,:x;-:x;,;:, x:zz/ 
00,,1'""2,;i Y 
(xx) 
E: rv;:,: /xx 
xxxxxxxx:zzxxxzxxzx 
DJ,,Jd•,r y,·, 
Yes 
No 
No 
xxx:-: 
3'ata:. 
5 
· ·es 
(xx)/ 
xx:o:xxxxxxxxxxxxx/ 
DD)E,JMYYY'i.' 
x;,::xxx;-:xxx xx:,::xx:•: / 
(xx) /xx 
XXX 
xx:-:;.-;xx;, zxxzz:-:x:;,x:-:xx 
DDMMMYYY·::.· 
{xx)/ 
Yes 
Yes 
Yes, 
o.a,c"• c. ,, 
zxxx 
Re- 
3 
solved 
Ne 
;,:::,::xxxxxxzx.:-:xx:,:xxx/ 
xxxxx;-:x.:-:x:{xxx;•:x I 
Or.going 
h·ith 
sequela 
e 
[a} Coded using MedDRA Dictionary (Version xx.xx: 
b] Relative tc ::he day of randocnizaL.on 
 
Prog·r,-arorrii:rig,- 1-:foteS: 
-Repeat:",.-:£'..or: _all ·'tt,E!at;,,i ht',g_roups, sQ,_i,t>by. T,reatment:, 9'±'(',.ll,fF, -- i:t·e·, _·pai-i,mt',. ·sta_rt ·,da_te .an,a. SOG: 
F-or:·•'ACtion· :tak,en·,',', ith ..study,· drug,_ ,-l s.t:, l_l dru_gs: t,ha_t ·app;y;.i_ arae'.ff.:th_ .p·r b:& l·e:_s_t,:u,_dy :drug - ·caused :AE coiu,-un. 
:7his 1-is_ting includes:.,a.1_1 ,AEs :_captured i_n the. study,· suc_h as -p_r_e-trea:tm nt..P.Es:- 
?r:ogram Na:ne: 
Date  Gener2ted: 
Page x of 
Listing Source: 


 
 
 
 
 
 
Repe ': fc-::: the £ollowi::1g disp:ays: 
List  r.g   2.6. .;'..l.i 
Ad,rerse :::venc:s Causir,g Discontir.uat:ion f.:::o:;r,_ Study T.:::-eatmer.t Safety Population 
Delete: 
:'Jote  to   Progra.rnmer:   Repea'.:.  for   all 
T.:::-eatment gro,.,ps. Sort b::,r Treatcc,ent  group,  site,  pac.ient,  start  dc.te  and  S:JC. 
Fo.:::- Actior: taken with study, drc.;g, list all ciru.g that apply, sa.me ,,,;ith probable study d:rug ca.t:.sed AE colu..,«n. 
Note to Prag ammer: This list.:i.r:g includes al ;:..Es  ca.pts1red  in  s;:he  study,  such  a.s pre-t::-:eac:ment  AEs. 
Footr,ote: :a Coded using t edD?A !)ictionary Ve.:::-sior: :<x.x::--:) 
[b] Relati·v·e  to 
he day of rarrdorr,ization 
 
Listing l6 ..c..l8 
Delete: 
Adve::-:se E;rer,ts ca,.;sir,g Ir,terr,.1ptior. ::rom St:_;dy ':::rea::::-,e::t Safety Po;n,;lation 
Note to Programrn.er: Repeat fc::: all Treatmer,t gro;.1ps. Sort :o,,.. ?reatc;:e::t groc,.p, site, pc.tier.t, stc.rt date a:..d soc. 
?o:r Acc:icr: taker.. v,;ith study, drug, list all cirugs t:'1at apply, sa,;:e \•;ith pro:Oa::)le stud',' d.:::-ug caused AE col:..1...Tfl.!7.. 
.rote to 2:::cg a.mrner; This listing includes all A:Ss capt,.1red in ::.he study, sc.:ch as pre-treatrr.er,t AEs. 
Footr:ote: :a Coded using MeciDRA Dictiona.c" {Ve:::-sic:i  ;o:. xxJ 
[bJ Relc.ti,,e to he day cf ::-:ar'.dosization 
 
Lis ting l6. . l.9 
De2-ete: 
Adverse Events :::ausing Dose Reciu.ction £rorn St"J.•:iy ?reat:r,ent Safety ?opu.lat::.on 
l ote to ?:::ogra=e::-:: Repeat for c.ll Treatment gro;;.ps. So:::t by Trea::.;nent group, site, patier.t, start date and so·:::. 
For Action ta;:en with study, drug, list all drugs that apply, sa;:;-,e ,,,,i::h probable study dru.g caused AE colu.:::-..r1. 
Note to ?:::cg arr --:-.er: This listing i.ncludes c.ll. AEs  captu:::ed  i:::  the  study,  s...-:.ch  as  pre-t:::eatment  ?.Es. Foctr,,ote: 
[a Coded using 1%ciDR.A Dictionary \'.Te:rsi0n xx.xx) 
[bJ Relative tc he day of rar-.domization 
 
Listing 16. . 20 
Delete: 
Treatmen-c-Re::.ateC Adverse Eve;. s Causing Dose Reductior: :Eron Study Treatment Safety Populatior:. 
Note tc P:::-og:::::as.-ne:r: ?,epec.t for all Treatment ;-roups. So:rt by ':'reat:ner.c: g:roup, site, patient, stc.:rt date and s-::x.::·. 
For P.ction t.-'-"ken ·,;::..th stLldy, drug, list all drugs tr',at apply, s2.ccte with ;,:roDable study dru.g caused AE colu..--n.n. 
Note to Prog a:r-.:ne:r: This listir1g r,cludes c.ll .n.ss capt.c:red in the study, such as  pre-treatrn.ent  AEs.  
Foo.:.ncte: [a Coded using ::--led ?.A ictior,ary (Ve::-:sicc. :<:x.xx) 
,o; Relati;re to he day of rando:nizat or; 


 
 
 
 
 
 
 
 
 
 
 
 
 
Stop Date 
(day; [b) 
Tiffie/ 
l),..,-C-ac.-'.v,!. 
 
 c.: ...... : c..-,,s: 
 
 
St.Ll.dy 
drug 
  
(day_s) 
 
 
xx 
xxx/1•'./45/ 
XXX 
xxx:,;:xz:- x:-:zxxx;,:xxxxx 
xxxx:o:;,;:x:-:xxxxxvxx/ 
iJD:":c"J1'1vvvy 
(z :) 
'-E'..:M"-' 
r;o 
':'es 
Yes, 
c:2::::- o_,_c 
xx;,: 
Re- 
solved 
,; 
xxxxxz;,:xxxxx:,::::x/ 
;'<D\IMl,l\'V'fV 
(zx) 
-,;:v·-·;,··.;;, -..·••:,••,:y·• ,·r•:·,;:vxx 
i-i :Mi"'. /xx 
DDM11i,1YYT-. 
Yes 
r:;c 
I'i:::: 
;-:;,;:zz 
:atal 
5 
(xx)/ 
xxxxxxxxxzx:-:>:x:o;:x/ 
 D'.-,'.M:-'.\'V\"V 
·r,;:·,::zzyy:,•· v:-:v -:xz/ 
(xx) /xx 
::--:x 
x:-<z 
xzz:-:zxx;-..::xzxxzxxx);xx 
xxxxxxxxxxx:s:xxxxx/ 
slDM!-1lr,, 
'.:n:)/ 
Ongoing 
Yes 
Yes 
Yes, 
''cc-:  :·::::;::: 
x:-:xx 
Re- 
solved 
,-,it , 
3 
x:-::xxxxxxxxx:s:xxx/ 
sequela 
  
e 
 
'.aj Coded using Me6DRA Dictiona:::-::· (Vel'."sion xx.xx) 
[bi Relative to the day cf l'."ar,dor;-;i::ac.:i.o" 
 
P,rog_r-a.imni,ng _N_oteS: 
-?-e_p at- f_or a:11 Treatment· gio1lps. _1fort'"by --_Treatm,mt, --gr,,9up/--Sf t'e-;_,, _patient, -_st<(:tt -_a<i te_- and, s,ac. 
F,oi'·,Action    taken   with   study,    drug.  list all 
drugs that ,:apply:-;_--,pame-with pro_bable s,t"lidY dru:g caused' AE colµ:inn. 
Program Name: 
Listing Source: 
Date Gene::-ated: 
Page x of y 
Listing l6.2.2l 
Serious   Ad0 _re  r  s  e    Eve:it.s 
$af'a+.y ;;, :;::,u' a-,..; "' 
Treat.me:;::. g::::o'-'.p: Treat.:1ent 
Site 
p--,..; """".,.. 
System Organ C.1.ass/ 
Sta:::t Date ',r,:,a.,.......,e.,.,, 
AE is due to 
=':cobao..:.e 
Action 
Ou.tcorr,e 
NC:- 
/Sex/Age/ 
Preferreci Term/ 
(day.\ 
:-,cc.e_ge.,,.., 
. .r. ·e:::-, '::.>  
$-,..,,,..;::, rl-'l'; 
Taken 
CTCAS 
Race 
··e:cbatir:, :a; 
Tiffie 
disease or 
cac:sed AE? 
wit!"': 
Grade 


 
 
 
 
 
 
 
 
 
 
T:reatmer,t group: Treat.«ent 
Listing    16.2.22 
Laboratory FinCings - Bone Marrow 
Safety ?op..:.la ion 
 
Site 
.::atient' 
/Sex/;:,.ge 
C"7' e ,-" S"' 
eye.le 
':isit 
Date  (de: 
[aj 
Type of 
e;,:amination 
b.1..as:: 
in 3one 
11arro,,· 
.Auer 
Respo;:;se 
Rods 
  
/Race, 
 
zx 
:,,,:.:x/M/ 45 
Ir,d;_,ct.ion 
3aseline 
DJ::01-:'.l'-ri·::·yy (  l) 
/xxx 
x:,x;.: 
DD11EI::--'.Y'-'... iY 
(xx·, 
::. i : ! 
Bi:::::_psv 
xx 
xx 
 
xx 
xx 
C? 
 
rO""'::-'' "',-,=, 
remissionj 
 
 
 
 
 
 
 
[a] Relative tc the day of rando:.,ization 
Prdgr:,axb.;nin,j .HOteS: 
Rep·eat ·for· ·ail .T.reat!'n,c;nt groups, Soit ·by·_. -r·reatni:::ht group, ·site, p·atien"t: :and. "tris:'3.·-t"-: 
Progran Nane: 
Listing Sci..:rcf>. 
Date   Ger,erac:ed; 
Page x 8£ 


 
 
 
 
 
 
 
Listing 16.2.23 
Laboratory    Fir,dings 
:-',e,T-atology i>.'itl'. C3C 
Safety Popula"'.:ion 
 
T:ceat:r,ent group: Treat:Teer;t 
Site 
?atient 
/Se;z/P..ge 
Cycle 
'hsit 
Col2.ection 
··,,,,.._,
Date !day) [a] 
,s ob;,., 
W3C 
Platelet 
Cou:-:t 
Neutrcp::ils 
Absolate 
Seg. 
Nec,trophils 
/?-ace 
Count (ANC'.) 
,/3ands 
c.:.,,,uc- apr,; 's 
 
xx 
xxx/'c-1/ 45 
'"ci"-:::--r' ,---,,, 
Baseline 
DDMM'.·lYYYY 
xx 
xx 
xx 
/;-:; X 
z :xx 
nrn1::,1r-:YYYY (xx) 
xx 
zx 
xx 
xx 
xx 
 
 
 
 
 
 
 
[a] Relative ::.o t:ne Cay of ;:"a:-:cio:mizatiou 
Pr'cigrammi:r1g Note _-:- 
Repeat-:for al-.l T.reatmefrt groups·, S6it )?Y.' Trea:t:inib:f:.. 9":Coup, site, patiei-rt ·k:Ud 'Visit. 
Prograrr:. Kame: 
Date Generated: 
Listir,g- Source: 
 
 
 
 
 
 
 
 
 
 
Page x o.:' 


 
 
 
 
 
 
 
 
 
 
 
T:::eatment group: Treat::1eict: 
Listing 16.2.24 
Laborato::-y Fir,dir,gs - Coag,..1.latior, 
Safet·,, ?opulation 
 
Site 
?atient 
/Sex/Age 
 
Cycls 
VlSl"C 
:::o.llection 
Date (day) [a] 
 
An,::i-factor 
xa 
 
?1' 
aP:T 
:NR 
t  :· ::'.. 0·vse:-::. 
D-diner 
  
/Race 
 
 
xx 
xxx/M/45 
/xxx 
, na'"._,  : GY. 
saselh1e 
,.,o:,,:-;u 
xx 
;n: 
xx 
x:-: 
;-::,: 
:•:x 
X:<XX 
1.;C;,;:,·: ffYYY   (xx) 
xx 
xx 
xx 
xx 
x:;: 
 
 
 
'a· Relative to the da:,r ::Jf Yandomizatior, 
P:rog'rar!lTtiTlg'-) _O_teS·_: 
Repeat Ioc-all· Treatment g·roups. Sort by_. 7-reatm8nt··g:fo_up, site;:_-,pa:t_i&nt-"--arid visit. 
?Ycgram Name: 
Lis-::ing Source: 
Date Generated: 
Page x of 


 
 
 
 
 
 
 
 
 
 
 
Treat:.,erit 9 
 
 
 
 
£ou_p: Treat,11ent l 
:;:,isti:.:::g 16.2.25 
Laborato;:"y ?i:::dings - Sers,: Che:r,istry ?art 
Safety i?opulatior:. 
 
Site 
Patient 
/Sex/Age 
/Race 
Cycle 
Visit 
Collectior. 
Date (day) taJ 
A'b·L7l:" 
Tor:al 
?:::-otein 
Total 
Bilirubi::-i 
Blood 
Drea 
Nitrogen 
Seru.o-n 
C.r-eatin 
-ine 
Sodiu."'.l 
Pot- 
assiw-:-, 
xx 
xxx/?:-5/45 
/xxx 
Ir:.di..:_ction 
Baseline 
xxxx 
DD:"1Mll:YYYY ! l) 
DDMMNYYYY (}'.X) 
xx 
xx 
xx 
:,:x 
xx 
xx 
;,c;x 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
[a} Relative to the day of rando:Ttiza-::ion 
PrOgr·airiJr,.it g· Notes.: 
Repeat·. for:·.a11 •'.l'Teat.-nent groups·. •_S6_.rt)i::{,:.Treatmerit group,. :·si-.t.e,. ·patient.-an,ct· vi._S.ft,. 
Program Narae: 
Listi:1g Sot.:..rce: 
Date   Generated: 
Page x of 


 
 
 
 
 
 
 
Listing  ::._6.2.26 
Laboratory Findings 
Serum  Cherr.istry  ?art 2 
Safety Pop,.:.lation 
 
 
 
 
I 
 
 
 
 
 
 
[a] Re.1.ati·v·e to the Cay of randorr:.izatior.  
P,io_g_timri1in_g_ -Nbt:eS'! 
Rei,e"ci't-£0'1'.' :all "freatment groups.-. ·sort by_ Treatment ._grcup_, s-ite", p-2.tient aii.d· visit. 
Prograr,, Name: 
Listing Source: 
:Jate   Generated: 
Page x of y 
Treatment 9-ro;i:9: Treat:,1ent 1 
Site 
Patient 
Cycle 
\:.'csit 
l./"' 7    "'   i  -, 
Calciur:: 
.D..lkaline 
::Jric 
SGOT 
SG?T 
1DE 
/Sex/Age 
Cate ·:'daJ) 
[a] 
Phosphatase 
Ac.id 
/AST 
f r.1..,,,
 
 
/ ace 
xx 
xxx/:-1/ 45 
 ,. ;.. '-. : o,·  
3ase.line 
om,n,1t,1YYYY ( l) 
xx 
xx 
xx 
xx 
x:-:: 
xx 
/xx:-: 
xxxx 
DD1•ltfc'.,JYYYY {xx) 
xx 
xx 
x;,:; 
xx 
xx 
xx 


 
 
 
 
 
 
 
List in; lE.2.27 
i??( listing 
Safety  ?opulation 
T:reat ,er,t g:roup: Treatment 
 
Site 
Patient/Age/Sex 
Visit 
Date  (d2y) 
PK Parar:sete:r 
Pf. value 
  
a 
zx 
xzx/xz/F 
zx 
zz 
xx 
xx 
 
 
 
 
 
 
 
[a]      Re l a t  i--0   e   to     the 
day     cf     randor::.ization 
Pr,cgr --n,-rcing ·Not_es-:: 
Repeat .for -all _T_.reat,m'2nt>9'i:oiiP.s-:,,-,t,in't by Treatment- group, -:si_te., patien\::an·a_:v:iSit-. 
-;:,,..,. 7.,.."'"' 7-,.,,c· 
Listing Source: 
Date   Gene:rated: 
2age x of 


 
 
 
 
 
 
 
Listing 16.2.28 
Vital   Signs   
Safety Population 
 
s'reat:;1e:1t group: T:::eatment 
 
Site 
?atient 
Visi;:: 
Date Time (day) '.a] 
/Sex/Age 
 
 
Systolic BP 
\ibl   •.g: 
 
 
Diasc:olic 32 
:rmn :-tg) 
 
 
'leart Rate 
(beat/min) 
 
 
Weight 
(kg) 
 
 
Eeight 
(cm) 
  
/Race 
 
xx 
xxx/1-1/ 4 .S 
xx :x:,:xx 
/xxx 
JJMMMY.Y.·-:.y HE:ME (xx) 
XXX 
XXX 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
[a] Relative to the dc.y of .::ar,dorcization 
Pr69'faTiliiling,-Not'e,'s:: 
1<:epeat £cr_,--E.l1 T.teatment' gl:'o_ups. sOrt by Tie:a:tment:_g,:i.:-Oijp, 'sfre:, pati'-et-it and: vis-it. 
?rogram Name: 
Listi:::g Source: 
Da"'.:e Generated: 
Page x of Y 


 
 
 
 
 
 
 
 
 
 
 
Treatment group: Treatme,,t 
List.ir,g 16 2.29 
ECG ?,esu ts 
Sa::"ety Pope:: ation 
s. ::.,te Patient 
/Sex/Age 
/?-ace 
Visit 
.i".ssessnent:: 
Date Tir;-,.e 
(da_;[) taJ 
ECG 
_performed? 
..Z:..ny clinically 
sigr,.ificant 
"'br,or:na2-i t::ies? 
 
xx 
xxx/t,;/ 45 
xxx 
/xxx 
XX}'. 
 
DDMMMY 
HH:YJM xx;· 
DDMMMY YY 
HH:r1M    x:-:' 
 
y,33 
 
i'io, ?artial 
refusal 
 
Yes 
 
xx 
xxx/F/45 
xx:,: 
/:-:xx 
DDMMl·1YY'!."Y 
H2:t1M (:-:x) 
::es 
-Jo 
XX}: 
DDMM.!Y:YYY 
HE.!"iM (:<:x) 
Yes 
No 
 
 
 
 
[aJ ?,elative t::o the day of ra'1.do::nizat::icn 
PrCi'gri:l.rrtmfn_g_ ·!-:jO;te:s; 
R€pe:,i :.:fO:r,:.a_l-_1 .T.reatmE!Ut :g:r_o;jps,.. Sort by .T:ti:-i_Ei-trrient ·group·, :site\ ::t,a:tie:nt_:·a_Il_d :;:'.isi.t:: 
?:::og::::a:m. Name; 
L ..stirrg   Sou:::ce: 
Date Ger::erated: 
?age x of Y 


 
 
 
 
 
 
 
Treat.me21t. g:::-oup: Treatment 1 
:ist.'.r1g 16.2.30 
?hysica2. Examination ?,esult.s 
Safety Population 
 
Site 
?atient 
Visit 
Assessrrcent Date Time 
Was 
Body 
?esults Normal 
Specify 
/Se:-:/Age 
/Race 
(day) [a] 
done? 
Syste2. 
Examined 
o Ah'"'O'""''T'2 7?  
if 
J.:..bnormal 
x: 
X)'.X/M/45 
/,-:xx 
3aS8line 
DDlC:MMYYYY HH:t1!-'l (xx) 
Yes 
Cardio--,-asc 
ular 
':Jo:::mal 
RepiratcJr· 
Ab:r;orr,al 
·,•:•::-:x 
Gastroir,te 
stinal  
Skin 
(0-ther 
?,JC:::-:na; 
:,Jormal 
t:l.a:1 
pri:;;-,.ar 
site o 
infect on} 
:'luscc.:losh:e 
let.al 
E"'°'or- ; .,--..,, 
No:::r:2 
'•,:o:::rr,a- 
Ne·ccrolcgic 
:-Jormal 
al 
HEElsT 
Jo.::-sal 
Genitourin 
ary 
No:::mal 
Wee:-: x 
"DEMMYYYY .EE: 111":: (x;-,:) 
No 
i one 
[a] ?elative to the day of rando:nization 
Progr,amtr,i-rig'Jfotes: 
-Repeat_-:fcr,_  ll 
T_r,eatme,nt' - = ups._ 'S◊-r-t::- y/I',f "? rnent -_-group, site pat,ieiit- and ,vi_sit_. ◊-fl- Y_::ptes_e_nt abTlortnal bO'dy s:/stems'. If all 
body systems are,normal at -a visit;. output '_None'--<-i_n,-,_Body System iTonorw..a:Uti•es-,cc-lurtm. for the visit-. 
... og..c.-"   Ne.me. 
Listing Source: 
Date   Generated: 
Page z of y