Amonafide in Combination With Cytarabine in Secondary AML

NCT ID: NCT00273884

Last Updated: 2007-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2009-04-30

Brief Summary

This protocol is designed to assess the safety and efficacy of amonafide in combination with cytarabine in subjects with previously untreated secondary AML.

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

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Amonafide L-Malate

Intervention Type: DRUG

Cytarabine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologic diagnosis of AML (≥20% blasts of myeloid lineage in bone marrow), with FAB classification other than M3, secondary to either:

1. Known and documented exposure to prior leukemogenic chemotherapy or radiotherapy, OR

2. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xanthus Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Principal Investigators

Steven Allen, MD

Role: PRINCIPAL_INVESTIGATOR

North Shore Hospital

Locations

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

City of Hope National Medical Center

Duarte, California, United States

UCLA Medical Center

Los Angeles, California, United States

Scripps Cancer Center

San Diego, California, United States

University of Colorado Health Sciences Center, Anschutz Cancer Center

Aurora, Colorado, United States

University of Florida Health Science Center

Gainesville, Florida, United States

Northwestern University, Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

St. Francis Cancer Research Foundation (formerly Indiana Oncology Hematology Consultants and American Health Network of Indiana LLC, Oncology Division)

Indianapolis, Indiana, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

MUSC - Hollings Cancer Center

Charleston, South Carolina, United States

Baylor University Medical Center

Dallas, Texas, United States

West Virginia University Medical Center

Morgantown, West Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Vancouver General Hospital

Vancouver, British Columbia, Canada

London Regional Cancer Program, London Health Science Center

London, Ontario, Canada

Countries

United States; Canada

Other Identifiers

0001A3-200-GL

Identifier Type: -

Identifier Source: org_study_id