- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00541866
Safety and Tolerability Study of Voreloxin and Cytarabine Combination in Acute Myeloid Leukemia in Humans
Phase 1b/2, Open-Label, Multicenter, Dose-Escalating, Clinical Study of the Safety, Tolerability, and PK and PD Profiles of Voreloxin Injection in Combination With Cytarabine in Patients With Relapsed or Refractory AML
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Colorado
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Denver, Colorado, United States, 80218
- Rocky Mountain Cancer Centers
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Denver, Colorado, United States, 80218
- HealthONE Presbyterian/St. Luke's Medical Center
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Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center
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Illinois
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Chicago, Illinois, United States, 60611
- Northwestern Memorial Hospital
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Chicago, Illinois, United States, 60611
- Northwestern Medical Faculty Foundation
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Indiana
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Indianapolis, Indiana, United States, 46206
- Indiana University Cancer Center
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Maryland
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Baltimore, Maryland, United States, 21205
- Johns Hopkins University - Sidney Kimmel Cancer Center
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New York
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New York, New York, United States, 10065
- New York Presbyterian Hospital-Weill Cornell Medical College
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Texas
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Houston, Texas, United States, 77030
- MD Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
KEY INCLUSION CRITERIA
- Relapsed or refractory AML subtypes defined by WHO, except acute promyelocytic leukemia. Relapsed/refractory disease may be de novo AML or secondary AML
- Treated with one to threee induction/reinduction AML regimens, prior induction or consolidation therapy with cytarabine allowed
- At least 10% blasts by BM biopsy or aspirate
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Clinical laboratory values of a) Serum creatinine ≤1.5 mg/dL and calculated or measured creatinine clearance (CRcl) of ≥50 mL/min, b) Total bilirubin ≤1.5 X upper limit of normal and c) Aspartate aminotransferase (AST) or alkaline phosphatase ≤2.5 X ULN.
KEY EXCLUSION CRITERIA
Patients with:
- Allogenic bone marrow transplant/stem cell transplant
- Persistent, clinically significant, chronic toxicities from prior AML therapy that would contraindicate the patient's participation in the clinical study due to safety concerns or compliance with study procedures
- Acute promyelocytic leukemia
- Disseminated intravascular coagulation
- Active infections, unless adequately treated with antibiotic, antiviral, or antifungal agents within in 7 days before Induction Day 1
- Active central nervous system involvement by AML
- Other active malignancies or other malignancies within the last 12 months except nonmelanoma skin cancer or cervical intraepithelial neoplasia
- A requirement for hemodialysis or peritoneal dialysis
- A history of myocardial infarction within the 3 months before treatment with vosaroxin
- A history of cerebrovascular accident/transient ischemic attack within the 3 months before treatment with vosaroxin
- A thromboembolic event (deep vein thrombosis or pulmonary embolus) within 28 days before treatment with vosaroxin
- Investigational products taken within 28 days before treatment with vosaroxin, and non-investigational cancer therapies or radiation therapy within 14 days before treatment with vosaroxin, with the exception of hydroxyurea.
- A known intolerance to cytarabine or known allergy to D-sorbitol or methanesulfonic acid (excipients used in vosaroxin)
- Prior exposure to vosaroxin
Any other medical, psychological, or social condition that contraindicates their participation in the clinical study due to safety concerns or compliance with study procedures in the opinion of the Investigator,or Sunesis Medical Monitor
In addition:
- Women who are pregnant or breastfeeding
- Women who are of childbearing potential or male patients who had partners of childbearing potential who were unwilling to use an approved, effective means of contraception according to the study site's standards
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Voreloxin injection and cytarabine
Dose-escalation Phase
Expansion Phase
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Dose-escalation Phase
Expansion Phase The MTD determined in the dose-escalation phase was used in the expansion phase.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
Time Frame: From start of treatment (Day 1) through Induction Day 29 or the start of reinduction, whichever occurred first.
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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.
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From start of treatment (Day 1) through Induction Day 29 or the start of reinduction, whichever occurred first.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
All Cause Mortality
Time Frame: 30 and 60 days
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Mortality of those patients enrolled in the study and receiving intervention
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30 and 60 days
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Remission Rates (CR+CRp)
Time Frame: Monthly after the end of treatment for the first year, then every 2 months thereafter for upto 2 years
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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. |
Monthly after the end of treatment for the first year, then every 2 months thereafter for upto 2 years
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Leukemia-free Survival (LFS)
Time Frame: 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.
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Leukemia-free survival is censored at the last known alive date without report of relapse.
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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.
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Overall Survival
Time Frame: 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
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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.
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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
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Sunesis Medical Monitor, MD, Sunesis Pharmaceuticals
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Cytarabine
Other Study ID Numbers
- SPO-0012
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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