Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory AML (VALOR)
|Acute Myeloid Leukemia||Drug: vosaroxin + cytarabine Drug: placebo + cytarabine||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase 3, Randomized, Controlled, Double-Blind, Multinational Clinical Study of the Efficacy and Safety of Vosaroxin and Cytarabine Versus Placebo and Cytarabine in Patients With First Relapsed or Refractory Acute Myeloid Leukemia (VALOR)|
- Overall Survival [ Time Frame: Up to 5 years or duration of study ]Vosaroxin + cytarabine patient survival versus placebo + cytarabine patient survival
- Complete Remission (CR) Rate Based on Modified International Working Group (IWG) Criteria. [ Time Frame: Up to 5 years or duration of study ]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.
- All Cause Mortality [ Time Frame: 30 Days ]Vosaroxin + cytarabine mortality versus placebo + cytarabine mortality
- All Cause Mortality [ Time Frame: 60 Days ]Vosaroxin + cytarabine mortality versus placebo + cytarabine mortality
- Overall Remission (OR) Rate Based on the IWG Response Criteria [ Time Frame: Up to 5 years or the duration of the study ]
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.
- Event Free Survival (EFS) [ Time Frame: Up to 5 years or duration of study ]
- Leukemia-Free Survival (LFS) [ Time Frame: Up to 5 years or the duration of the study ]Durability of remission (CR) assessed by LFS
|Study Start Date:||December 17, 2010|
|Study Completion Date:||March 1, 2017|
|Primary Completion Date:||September 26, 2014 (Final data collection date for primary outcome measure)|
Experimental: Group A: vosaroxin + cytarabine
vosaroxin (short IV infusion within 10 minutes) on days 1 and 4: cytarabine on days 1 through 5; a maximum of 2 cycles of Induction and 2 cycles for Consolidation
Drug: vosaroxin + cytarabine
Vosaroxin days 1 and 4: 90 mg/m2 for induction 1; 70 mg/m2 for all other cycles
Cytarabine 1 g/m2 daily on days 1-5 (IDAC)
Placebo Comparator: Group B: placebo + cytarabine
placebo (short IV infusion within 10 minutes and volume matched to vosaroxin) on days 1 and 4: cytarabine on days 1 through 5; a maximum of 2 cycles of Induction and 2 cycles for Consolidation
Drug: placebo + cytarabine
Placebo days 1 and 4: volume matched to vosaroxin
Cytarabine 1 g/m2 daily on days 1-5 (IDAC)
Other Name: control
The study includes additional objectives to ones listed above as Outcome Measures. These additional objectives also compared treatment groups in the following:
CR + CRp rate, defined as CR + CRp based on modified IWG response criteria.
Combined CR rate (CR+CRp+CRi).
Percentage of patients who have post-treatment (subsequent) transplantation.
Percentage of patients who received subsequent non-protocol therapy (including transplantation).
Safety and tolerability.
In keeping with FDA guidance for adaptive trial designs, the study incorporated an independent DSMB (Drug Safety Monitoring Board) to address potential uncertainty concerning the true treatment affect between the treatment groups and to address a deterioration of power from a small difference. Sunesis remained blinded and had no involvement in the interim data analysis, interpretation, or adaptive design. Based on the results of the interim data analysis the DSMB recommended an increase in the target number of deaths from 375 in 450 patients to 562 in 675 patients which based on a 5% dropout rate increased enrollment from 475 to 712.
The primary analysis was performed when the target number of deaths had been achieved based on a permuted block randomization procedure, stratified by disease status (refractory, first relapse with duration of first CR or CRp ≥ 90 days and < 12 months, or first relapse with duration of first CR or CRp ≥ 12 months and ≤ 24 months), age (< 60 years or ≥ 60 years), and geographic location (US or outside US). The study included periods of screening, treatment / hematologic recovery, post-treatment follow-up, and long-term follow-up for survival.
Follow-up was monthly during the first year, every 2 months during the second year, and every 3 months thereafter until death, withdrawal of consent, or loss to follow-up, whichever occurred first. Long-term follow-up began for all patients when the required number of deaths for primary analysis had been met; thereafter, survival data were collected every 4 months until death, withdrawal of consent, or loss to follow-up, whichever occurred first.
The long term follow-up for this study continues at this time and the September 2014 date reflects database lock for primary analyses reflected in the Results Section. During long term follow-up Sunesis is not collecting Adverse Events.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01191801
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|Study Director:||Linda Neuman, MD||Sunesis Pharmaceuticals|