Amonafide in Combination With Cytarabine in Secondary AML

February 16, 2007 updated by: Xanthus Pharmaceuticals, Inc.

Phase 2 Open-Label Study of Amonafide L-Malate in Combination With Cytarabine in Subjects With Secondary Acute Myeloid Leukemia (AML)

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

Study Overview

Status

Completed

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

Interventional

Enrollment

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E3
        • Vancouver General Hospital
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program, London Health Science Center
    • Alabama
      • Birmingham, Alabama, United States, 35294-3300
        • University of Alabama at Birmingham Comprehensive Cancer Center
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • Los Angeles, California, United States, 90024
        • UCLA Medical Center
      • San Diego, California, United States, 92121
        • Scripps Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80010
        • University of Colorado Health Sciences Center, Anschutz Cancer Center
    • Florida
      • Gainesville, Florida, United States, 32610-0277
        • University of Florida Health Science Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University, Robert H. Lurie Comprehensive Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • St. Francis Cancer Research Foundation (formerly Indiana Oncology Hematology Consultants and American Health Network of Indiana LLC, Oncology Division)
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Memorial Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0848
        • University of Michigan
    • Nebraska
      • Omaha, Nebraska, United States, 98198 7835
        • University of Nebraska Medical Center
    • New York
      • Buffalo, New York, United States, 75246
        • Roswell Park Cancer Institute
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • MUSC - Hollings Cancer Center
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506-9162
        • West Virginia University Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College Of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
- To determine the rate of complete remission with or without complete hematopoietic recovery (CR + CRi).

Secondary Outcome Measures

Outcome Measure
Determine the median duration of complete remission with or without complete hematopoietic recovery (CR or CRi)
Determine the proportion of subjects remaining in complete remission (CR +CRi) at 6 months, at 12 months and at 18 months
Determine the median duration of overall survival (OS)
Correlate clinical responses and duration of responses with specific cytogenetic abnormalities
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
Define the safety profile and confirm the acceptability of amonafide and cytarabine
Correlate PK exposure of amonafide and acetylation of amonafide with safety and efficacy assessments in individual subjects

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Steven Allen, MD, North Shore Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2005

Study Completion

April 1, 2009

Study Registration Dates

First Submitted

January 5, 2006

First Submitted That Met QC Criteria

January 5, 2006

First Posted (ESTIMATE)

January 9, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

February 19, 2007

Last Update Submitted That Met QC Criteria

February 16, 2007

Last Verified

February 1, 2007

More Information

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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