Safety and Tolerability Study of Voreloxin and Cytarabine Combination in Acute Myeloid Leukemia in Humans

Phase 1

Completed

Conditions: Acute Myeloid Leukemia

Interventions: Drug: Voreloxin injection and cytarabine

Registration Number: NCT00541866

Lead Sponsor: Sunesis Pharmaceuticals

Brief Summary: This study will evaluate the safety and tolerability of voreloxin (vosaroxin) injection in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia.

Detailed Description: An open-label, Phase 1b/2 study using a dose-escalation design with expansion at the maximum tolerated dose (MTD) using 2 dosing schedules:

During the Schedule A dose-escalation phase, patients with relapsed or refractory acute myeloid leukemia (AML) enrolled in cohorts of at least 3 patients to identify the MTD. Begin with a starting dosing regimen of vosaroxin of 10 mg/m2 on Days 1 and 4 of each cycle in combination with a 24-hour continuous intravenous (CIV) infusion of cytarabine 400 mg/m2/day × 5 days. If none of the 3 patients or 1 of 6 patients experience a dose-limiting toxicity (DLT) at the vosaroxin starting dose, dose-escalate vosaroxin. If 2 of 6 patients experienced a DLT at the vosaroxin starting dose, reduce the dose of cytarabine to reduced to 200 mg/m2 (only case in which the cytarabine could have been reduced). The vosaroxin dose escalated following a modified Fibonacci schema.

For Schedule B dose-escalation phase, patients with relapsed or refractory AML enrolled in cohorts of at least 3 patients to identify the MTD. Begin with a starting dose regimen of vosaroxin of 70 mg/m2 on Days 1 and 4 in combination with cytarabine as a 2-hour infusion of 1 g/m2/day × 5 days. No reductions of cytarabine allowed in Schedule B. If none of the 3 patients or 1 of 6 patients experienced a DLT in the first cohort of Schedule B, escalate the dose of vosaroxin. If DLTs occurred in 2 of 6 patients during the starting dose, reduce the vosaroxin dose to 50 mg/m2.

For both Schedules, the highest dose at which fewer than 2 of 6 patients experienced a DLT during induction became the MTD and the recommended future dose.

Once the MTD of vosaroxin was determined for Schedule A, first relapse patients were enrolled in the expansion phase at that dose level to obtain additional safety and efficacy information. When the MTD of vosaroxin was determined for Schedule B, first relapse patients and patients with primary refractory disease were enrolled in the expansion phase at that dose level to characterize the safety and efficacy profile in this population.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 110

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Voreloxin injection and cytarabine	Voreloxin injection and cytarabine	Dose-escalation Phase * Schedule A: * Schedule B: Expansion Phase * Schedule A: * Schedule B:

Primary Outcome Measures

Name	Time	Method
Incidence of Dose-Limiting Toxicity (DLT) to Determine Maximum Tolerated Dose in Schedule A and Schedule B of Dose Escalation Phase (Group 1 and Group 2)	From start of treatment (Day 1) through Induction Day 29 or the start of reinduction, whichever occurred first.	Patients were treated in cohorts with escalating doses of vosaroxin administered in combination with cytarabine in Schedule A, and with vosaroxin in escalating doses in Schedule B. For both Schedules, the highest dose at which fewer than 2 of 6 (\<0.33) patients experienced a dose-limiting toxicity (DLT) during induction became the MTD and the recommended future dose.

Secondary Outcome Measures

Name	Time	Method
Remission Rates (CR+CRp)	Monthly after the end of treatment for the first year, then every 2 months thereafter for upto 2 years	Complete remission (CR) plus CR with incomplete platelet recovery (CRp) per The IWG criteria for remission modified by Sunesis, assessed by investigator. CR is defined as \>1000 Neutrophils (ul), \>100,000 Platelets (uL) and \<5 BM Blasts (%); CRp is defined as \>1000 Neutrophils (ul), \<=100,000 Platelets (uL) and \<5 BM Blasts (%); CRi is defined as \>1000 Neutrophils (ul), \<100,000 Platelets (uL) and \<5 BM Blasts (%); Investigators were to determine a response category for each patient by examination of bone marrow and blood counts at the time of hematologic recovery after induction or reinduction. Investigator assessment categories included CR, CRp, CRi (CR with morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.
Leukemia-free Survival (LFS)	From time of the start of CR or CRp to the earliest date of relapse, commencement of reinduction therapy, or death, assessed monthly up to 2 years after the end of study visit.	Leukemia-free survival is censored at the last known alive date without report of relapse.
Overall Survival	Time between the date of first study treatment and the date of death due to any cause for upto 2 years after the end of study visit	Overall survival is censored at the earlier of the cutoff date for analysis and the last date known to be alive for patients not known to have died.
All Cause Mortality	30 and 60 days	Mortality of those patients enrolled in the study and receiving intervention

Trial Locations

Locations (9): HealthOne Presbyterian/St. Luke's Medical Center
🇺🇸
Denver, Colorado, United States
Rocky Mountain Cancer Centers
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Denver, Colorado, United States
H. Lee Moffitt Cancer Center
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Tampa, Florida, United States
Johns Hopkins University - Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
MD Anderson Cancer Center
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Houston, Texas, United States
Northwestern Medical Faculty Foundation
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Chicago, Illinois, United States
Northwestern Memorial Hospital
🇺🇸
Chicago, Illinois, United States
Indiana University Cancer Center
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Indianapolis, Indiana, United States
New York Presbyterian Hospital-Weill Cornell Medical College
🇺🇸
New York, New York, United States