NCT01191801

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

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)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 711 (actual)
• Sponsor: Sunesis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study compared treatment groups of patients treated with vosaroxin and cytarabine versus patients treated with placebo and cytarabine.

Detailed description

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.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
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)
DRUG	placebo + cytarabine	Placebo days 1 and 4: volume matched to vosaroxin Cytarabine 1 g/m2 daily on days 1-5 (IDAC)

Timeline

• Start date: 2010-12-17
• Primary completion: 2014-09-26
• Completion: 2017-03-01
• First posted: 2010-08-31
• Last updated: 2018-08-22
• Results posted: 2017-05-09

Locations

124 sites across 15 countries: United States, Australia, Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, New Zealand, Poland, South Korea, Spain, United Kingdom