Trial Outcomes & Findings for Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory AML (NCT NCT01191801)

NCT ID: NCT01191801

Last Updated: 2018-08-22

Results Overview

Vosaroxin + cytarabine patient survival versus placebo + cytarabine patient survival

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

711 participants

Primary outcome timeframe

Up to 5 years or duration of study

Results posted on

2018-08-22

Participant Flow

320 patients enrolled in 30 US sites:391 patients enrolled at 71 sites outside of the US (Canada, Europe, Australia, New Zealand, and Republic of Korea)

Six patients were randomized but never received treatment due to death prior to beginning treatment: 4 assigned to receive vosaroxin/cytarabine; 2 assigned to receive placebo/cytarabine.

Participant milestones

Participant milestones
Measure	Group A (Vosaroxin/Cytarabine) Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
Overall Study STARTED	356	355
Overall Study COMPLETED	40	18
Overall Study NOT COMPLETED	316	337

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A (Vosaroxin/Cytarabine) Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
Overall Study Death	36	12
Overall Study Lack of Efficacy	176	258
Overall Study Adverse Event	9	8
Overall Study Protocol Violation	2	4
Overall Study Physician Decision	47	24
Overall Study Withdrawal by Subject	1	4
Overall Study Not Provided	45	27

Baseline Characteristics

Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory AML

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A (Vosaroxin/Cytarabine) n=356 Participants Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) n=355 Participants Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5	Total n=711 Participants Total of all reporting groups
Age, Continuous	61 years STANDARD_DEVIATION 11.51 • n=5 Participants	60.2 years STANDARD_DEVIATION 12.49 • n=7 Participants	60.6 years STANDARD_DEVIATION 12.01 • n=5 Participants
Sex: Female, Male Female	154 Participants n=5 Participants	163 Participants n=7 Participants	317 Participants n=5 Participants
Sex: Female, Male Male	202 Participants n=5 Participants	192 Participants n=7 Participants	394 Participants n=5 Participants
Region of Enrollment Hungary	8 participants n=5 Participants	11 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment United States	161 participants n=5 Participants	159 participants n=7 Participants	320 participants n=5 Participants
Region of Enrollment United Kingdom	15 participants n=5 Participants	10 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Spain	9 participants n=5 Participants	8 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment New Zealand	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Canada	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Czech Republic	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Austria	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Belgium	17 participants n=5 Participants	19 participants n=7 Participants	36 participants n=5 Participants
Region of Enrollment Poland	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Korea, Republic of	10 participants n=5 Participants	5 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Italy	20 participants n=5 Participants	18 participants n=7 Participants	38 participants n=5 Participants
Region of Enrollment Australia	25 participants n=5 Participants	20 participants n=7 Participants	45 participants n=5 Participants
Region of Enrollment France	38 participants n=5 Participants	50 participants n=7 Participants	88 participants n=5 Participants
Region of Enrollment Germany	27 participants n=5 Participants	31 participants n=7 Participants	58 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years or duration of study

Population: The intent-to-treat (ITT) population which consists of all patients enrolled (randomly assigned to treatment group).

Vosaroxin + cytarabine patient survival versus placebo + cytarabine patient survival

Outcome measures

Outcome measures
Measure	Group A (Vosaroxin/Cytarabine) n=356 Participants Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) n=355 Participants Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
Overall Survival	7.5 Months Interval 6.4 to 8.5	6.1 Months Interval 5.2 to 7.1

SECONDARY outcome

Timeframe: Up to 5 years or duration of study

Population: The percentage of patients who achieved CR was adjudicated by the CPARR (Central Pathology and Response Review) panel using modified IWG response criteria. The outcome measure reflects the Intent to Treat Population.

Group A (Vosaroxin + cytarabine) patient CR as compared to Group B (placebo + cytarabine) patient CR. Complete remission (CR) is typically defined using IWG criteria as bone marrow blast count of less than 5% with adequate recovery of peripheral blood counts.

Outcome measures

Outcome measures
Measure	Group A (Vosaroxin/Cytarabine) n=356 Participants Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) n=355 Participants Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
Complete Remission (CR) Rate Based on Modified International Working Group (IWG) Criteria.	30.1 percentage of particpants Interval 25.3 to 35.1	16.3 percentage of particpants Interval 12.6 to 20.6

SECONDARY outcome

Timeframe: 30 Days

Population: Safety Population (705)

Vosaroxin + cytarabine mortality versus placebo + cytarabine mortality

Outcome measures

Outcome measures
Measure	Group A (Vosaroxin/Cytarabine) n=355 Participants Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) n=350 Participants Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
All Cause Mortality	7.9 percentage of Participants in the Group Interval 5.3 to 11.2	6.6 percentage of Participants in the Group Interval 4.2 to 9.7

SECONDARY outcome

Timeframe: 60 Days

Population: Safety Population (705)

Vosaroxin + cytarabine mortality versus placebo + cytarabine mortality

Outcome measures

Outcome measures
Measure	Group A (Vosaroxin/Cytarabine) n=355 Participants Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) n=350 Participants Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
All Cause Mortality	19.7 percentage of Participants Interval 15.7 to 24.2	19.4 percentage of Participants Interval 15.4 to 24.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years or the duration of the study

Population: Intent to Treat Population

Group A patient OR compared to Group B patient OR Overall Remission includes Complete Remission (CR), Complete Remission with incomplete platelet recovery (CRp), Complete Remission with incomplete blood count recovery (CRi), and Partial Remission (PR). Complete remission means bone marrow blast count of less than 5% with adequate recovery of peripheral blood counts as typically defined by the IWG. Both CRi and CRp refer complete remission but with incomplete blood count and platelet recovery, respectively. PR, or partial remission, refers to remission in which bone marrow contains blast counts between 5 and 25 percent.

Outcome measures

Outcome measures
Measure	Group A (Vosaroxin/Cytarabine) n=356 Participants Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) n=355 Participants Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
Overall Remission (OR) Rate Based on the IWG Response Criteria	37.9 percentage of participants Interval 32.9 to 43.2	18.9 percentage of participants Interval 14.9 to 23.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years or duration of study

Population: Intent to Treat Population

Outcome measures

Outcome measures
Measure	Group A (Vosaroxin/Cytarabine) n=356 Participants Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) n=355 Participants Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
Event Free Survival (EFS)	1.9 months Interval 1.6 to 2.2	1.3 months Interval 1.2 to 1.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years or the duration of the study

Population: Subset of Intent to Treat patients that have a Measured CR

Durability of remission (CR) assessed by LFS

Outcome measures

Outcome measures
Measure	Group A (Vosaroxin/Cytarabine) n=107 Participants Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) n=58 Participants Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
Leukemia-Free Survival (LFS)	11 Months Interval 8.3 to 14.3	8.7 Months Interval 6.5 to 18.0

Adverse Events

Group A (Vosaroxin/Cytarabine)

Serious events: 197 serious events

Other events: 354 other events

Deaths: 273 deaths

Group B (Placebo/Cytarabine)

Serious events: 125 serious events

Other events: 349 other events

Deaths: 288 deaths

Serious adverse events

Other adverse events

Additional Information

Judy Fox, Chief Scientific Officer

Sunesis Pharmaceuticals, Inc

Phone: (650) 266-3736

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	Group A (Vosaroxin/Cytarabine) n=355 participants at risk Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) n=350 participants at risk Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
Vascular disorders Venous thrombosis	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Blood and lymphatic system disorders Anaemia	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.57% 2/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Blood and lymphatic system disorders Febrile neutropenia	11.3% 40/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	7.4% 26/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Blood and lymphatic system disorders Neutropenia	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Blood and lymphatic system disorders Pancytopenia	0.56% 2/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Blood and lymphatic system disorders Pure white cell aplasia	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Blood and lymphatic system disorders Thrombocytopenia	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Atrial fibrillation	0.56% 2/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Atrial flutter	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Cardiac failure congestive	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Cardiomyopathy	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Diastolic dysfunction	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Left ventricular dysfunction	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Myocardial infarction	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Myocardial ischaemia	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Myopericarditis	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Tachycardia	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Endocrine disorders Diabetes insipidus	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Eye disorders Conjunctivitis	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Eye disorders Vitreous haemorrhage	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Anal fistula	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Caecitis	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Colitis	1.4% 5/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Diarrhoea	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Enteritis	0.56% 2/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Enterocolitis	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Gastric ulcer perforation	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Gastritis	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.56% 2/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Gastrointestinal inflammation	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Haemorrhoids	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.57% 2/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Ileitis	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Ileus	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Nausea	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Neutropenic colitis	0.28% 1/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Oesophagitis	0.85% 3/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.00% 0/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Periodontitis	0.00% 0/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	0.29% 1/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Stomatitis	3.4% 12/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	1.4% 5/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.

Other adverse events
Measure	Group A (Vosaroxin/Cytarabine) n=355 participants at risk Vosaroxin on Days 1 and 4 (90 mg/m2 induction 1; 70 mg/m2 all other cycles); cytarabine 1 g/m2 daily on Days 1 through 5	Group B (Placebo/Cytarabine) n=350 participants at risk Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5
Blood and lymphatic system disorders Anaemia	26.8% 95/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	29.7% 104/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Blood and lymphatic system disorders Febrile neutropenia	40.3% 143/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	27.7% 97/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Blood and lymphatic system disorders Neutropenia	19.7% 70/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	14.3% 50/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Blood and lymphatic system disorders Thrombocytopenia	24.8% 88/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	25.7% 90/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Atrial fibrillation	6.2% 22/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	4.6% 16/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Cardiac disorders Tachycardia	9.0% 32/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	8.3% 29/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Abdominal distension	5.6% 20/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	2.9% 10/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Abdominal pain	22.3% 79/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	13.1% 46/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Abdominal pain upper	8.7% 31/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	9.4% 33/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Constipation	38.3% 136/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	40.3% 141/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Diarrhoea	68.5% 243/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	34.6% 121/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Dry mouth	6.2% 22/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	3.4% 12/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Dyspepsia	13.0% 46/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	4.9% 17/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Dysphagia	5.6% 20/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	2.0% 7/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Haemorrhoids	8.5% 30/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	4.0% 14/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Nausea	61.4% 218/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	47.7% 167/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Oral pain	5.9% 21/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	1.7% 6/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Stomatitis	47.6% 169/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	18.3% 64/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Gastrointestinal disorders Vomiting	38.0% 135/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	20.9% 73/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
General disorders Asthenia	16.9% 60/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	12.3% 43/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
General disorders Chest pain	8.2% 29/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	5.4% 19/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
General disorders Chills	17.2% 61/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	13.1% 46/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
General disorders Fatigue	30.1% 107/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	26.9% 94/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
General disorders Oedema peripheral	27.0% 96/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	19.7% 69/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
General disorders Pain	5.9% 21/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	9.1% 32/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
General disorders Pyrexia	33.2% 118/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	30.3% 106/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Infections and infestations Bacteraemia	5.1% 18/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	1.7% 6/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Infections and infestations Oral candidiasis	5.1% 18/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	4.6% 16/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Infections and infestations Oral herpes	6.5% 23/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	1.1% 4/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Infections and infestations Pneumonia	6.2% 22/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	5.4% 19/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Injury, poisoning and procedural complications Procedural pain	2.3% 8/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	5.7% 20/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Injury, poisoning and procedural complications Transfusion reaction	5.1% 18/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	4.6% 16/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Investigations Alanine aminotransferase increased	8.2% 29/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	4.9% 17/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Investigations Aspartate aminotransferase increased	6.8% 24/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	4.6% 16/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Investigations Blood creatinine increased	5.1% 18/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	2.9% 10/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Investigations Platelet count decreased	6.5% 23/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	8.3% 29/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Investigations White blood cell count decreased	6.8% 24/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	6.0% 21/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Metabolism and nutrition disorders Decreased appetite	35.5% 126/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	16.9% 59/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Metabolism and nutrition disorders Fluid overload	5.1% 18/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	4.6% 16/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.
Metabolism and nutrition disorders Fluid retention	5.4% 19/355 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.	6.6% 23/350 • Adverse Event reported below reflects time from first patient randomization 17 December 2010 to database lock for primary analysis 26 September 2014. The Tables show Incidence of Treatment Emergent Adverse Events.