- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00273884
Amonafide in Combination With Cytarabine in Secondary AML
Phase 2 Open-Label Study of Amonafide L-Malate in Combination With Cytarabine in Subjects With Secondary Acute Myeloid Leukemia (AML)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a two-stage, open-label, phase 2, multicenter study of amonafide L-malate in combination with standard-dose cytarabine in subjects with secondary AML.
Amonafide is a DNA intercalating agent and inhibitor of topoisomerase II that has been extensively studied in patients with malignant solid tumors. Amonafide has also been studied in patients with AML. In three phase I clinical trials, amonafide demonstrated anti-leukemic activity, both as monotherapy and in combination with cytarabine. This protocol is designed to further assess the safety and efficacy of amonafide in combination with cytarabine in subjects with previously untreated secondary AML.
The duration of the study is approximately 42 months: enrollment approximately 18 months and subject duration up to 24 months
Study Type
Enrollment
Phase
- Phase 2
Contacts and Locations
Study Locations
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 4E3
- Vancouver General Hospital
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Ontario
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London, Ontario, Canada, N6A 4L6
- London Regional Cancer Program, London Health Science Center
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Alabama
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Birmingham, Alabama, United States, 35294-3300
- University of Alabama at Birmingham Comprehensive Cancer Center
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California
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Duarte, California, United States, 91010
- City of Hope National Medical Center
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Los Angeles, California, United States, 90024
- UCLA Medical Center
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San Diego, California, United States, 92121
- Scripps Cancer Center
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Colorado
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Aurora, Colorado, United States, 80010
- University of Colorado Health Sciences Center, Anschutz Cancer Center
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Florida
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Gainesville, Florida, United States, 32610-0277
- University of Florida Health Science Center
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Illinois
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Chicago, Illinois, United States, 60611
- Northwestern University, Robert H. Lurie Comprehensive Cancer Center
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Indiana
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Indianapolis, Indiana, United States, 46202
- St. Francis Cancer Research Foundation (formerly Indiana Oncology Hematology Consultants and American Health Network of Indiana LLC, Oncology Division)
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana Farber Cancer Institute
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Worcester, Massachusetts, United States, 01655
- University of Massachusetts Memorial Medical Center
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Michigan
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Ann Arbor, Michigan, United States, 48109-0848
- University of Michigan
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Nebraska
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Omaha, Nebraska, United States, 98198 7835
- University of Nebraska Medical Center
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New York
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Buffalo, New York, United States, 75246
- Roswell Park Cancer Institute
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke University Medical Center
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences
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South Carolina
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Charleston, South Carolina, United States, 29425
- MUSC - Hollings Cancer Center
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Texas
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Dallas, Texas, United States, 75246
- Baylor University Medical Center
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West Virginia
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Morgantown, West Virginia, United States, 26506-9162
- West Virginia University Medical Center
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- Medical College Of Wisconsin
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologic diagnosis of AML (≥20% blasts of myeloid lineage in bone marrow), with FAB classification other than M3, secondary to either:
- Known and documented exposure to prior leukemogenic chemotherapy or radiotherapy, OR
- Diagnosis of MDS for ≥3 months prior to study entry (prior BM slides documenting MDS must be available for central pathology review).
- Age 18 years or older.
- ECOG performance status ≤2.
- No prior induction chemotherapy for AML; at least 4 weeks since completion of prior chemotherapy for MDS. (Subjects with rapidly rising blast count may be enrolled within 4 weeks of prior cytotoxic chemotherapy).
- Fertile and sexually active men and women must use effective contraception throughout study. Women of childbearing potential must have a negative pregnancy test.
- LVEF ≥50% by MUGA or ECHO.
- Adequate renal function: serum creatinine ≤1.5 x ULN.
- Adequate hepatic function: total serum bilirubin ≤1.5 x ULN as well as serum AST and ALT ≤1.5 x ULN.
- Subject must be able to participate fully in all aspects of the trial.
- Subject must give voluntary, written consent and HIPAA authorization (US only).
Exclusion Criteria:
- Histologic diagnosis of FAB M3 AML (acute promyelocytic leukemia).
- Clinically active CNS leukemia.
- Known to be HIV positive.
- Prior induction chemotherapy for AML.
- Known active hepatitis B or C or other active liver disease.
- Any major surgery or radiation therapy within 4 weeks prior to study entry.
- Prior cytotoxic chemotherapy within 4 weeks prior to study entry.(Subjects with rapidly rising blast count may be enrolled within 4 weeks of prior cytotoxic chemotherapy).
- Persistent chronic non-hematologic toxicity from prior chemotherapy (other than alopecia) that is > than grade 1.
- Serious concomitant illness (e.g., active pulmonary infection, unstable angina or myocardial infarction within 3 months of study entry, congestive heart failure ≥AHA class 2, stroke within 3 months prior to study entry, uncontrolled hypertension, uncontrolled diabetes, actively bleeding gastric ulcer, etc.).
- Women who are pregnant or lactating.
- History of clinically significant allergic reactions attributed to compounds similar to amonafide or cytarabine.
- Prior enrollment on this trial.
- Any other known condition (familial, sociological, or geographic) or behavior (including substance abuse, psychological or psychiatric illness), which in the investigator's opinion would make the subject a poor candidate for this trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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- To determine the rate of complete remission with or without complete hematopoietic recovery (CR + CRi).
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Secondary Outcome Measures
Outcome Measure |
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Determine the median duration of complete remission with or without complete hematopoietic recovery (CR or CRi)
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Determine the proportion of subjects remaining in complete remission (CR +CRi) at 6 months, at 12 months and at 18 months
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Determine the median duration of overall survival (OS)
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Correlate clinical responses and duration of responses with specific cytogenetic abnormalities
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Define the population pharmacokinetic (PK) profile of amonafide and its metabolites when administered as an intravenous infusion daily x 5 days in combination with a standard-dose of cytarabine
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Define the safety profile and confirm the acceptability of amonafide and cytarabine
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Correlate PK exposure of amonafide and acetylation of amonafide with safety and efficacy assessments in individual subjects
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Steven Allen, MD, North Shore Hospital
Study record dates
Study Major Dates
Study Start
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Cytarabine
- Amonafide
Other Study ID Numbers
- 0001A3-200-GL
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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