Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Diseases

Neoplasms by Histologic Type

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

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

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

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)

vosaroxin + cytarabine

Placebo days 1 and 4: volume matched to vosaroxin

Cytarabine 1 g/m2 daily on days 1-5 (IDAC)

placebo + cytarabine

Linda Neuman, MD

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

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.

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)

De-identified data of individual participants experiencing Serious Adverse Events

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.

Durability of remission (CR) assessed by LFS

Vosaroxin + cytarabine patient survival versus placebo + cytarabine patient survival

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.

Vosaroxin + cytarabine mortality versus placebo + cytarabine mortality

Sunesis Pharmaceuticals

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 A (Vosaroxin/Cytarabine)

Placebo (volume matched to vosaroxin) on Days 1 and 4; cytarabine 1 g/m2 daily on Days 1 through 5

Group B (Placebo/Cytarabine)

Total

Age, Continuous

Sex: Female, Male

Hungary

United States

United Kingdom

Spain

New Zealand

Canada

Czech Republic

Austria

Belgium

Poland

Korea, Republic of

Italy

Australia

France

Germany

Region of Enrollment

Intent to Treat Population: Patients who were randomized.

Judy Fox, Chief Scientific Officer

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

Overall Survival

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory AML	NCT01191801	Acute Myeloid L...	vosaroxin + cyt... placebo + cytar...	18 Years -	Sunesis Pharmaceuticals
Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory AML	NCT01191801	Acute Myeloid L...	vosaroxin + cyt... placebo + cytar...	18 Years -	Sunesis Pharmaceuticals
Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory AML	NCT01191801	Acute Myeloid L...	vosaroxin + cyt... placebo + cytar...	18 Years -	Sunesis Pharmaceuticals

Spots Global Cancer Trial Database for first relapsed aml