Amonafide in Combination With Cytarabine in Secondary AML

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00273884
• Other study ID #: 0001A3-200-GL
• Status: Completed
• Phase: Phase 2
• First received: January 5, 2006
• Last updated: February 16, 2007
• Start date: August 2005
• Est. completion date: April 2009

Study information

• Verified date: February 2007
• Source: Xanthus Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Amonafide L-Malate

• Cytarabine

Locations

Country	Name	City	State
Canada	London Regional Cancer Program, London Health Science Center	London	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado Health Sciences Center, Anschutz Cancer Center	Aurora	Colorado
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	MUSC - Hollings Cancer Center	Charleston	South Carolina
United States	Northwestern University, Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	Baylor University Medical Center	Dallas	Texas
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida Health Science Center	Gainesville	Florida
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	UCLA Medical Center	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	West Virginia University Medical Center	Morgantown	West Virginia
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Scripps Cancer Center	San Diego	California
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Xanthus Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	- To determine the rate of complete remission with or without complete hematopoietic recovery (CR + CRi).
Secondary	Determine the median duration of complete remission with or without complete hematopoietic recovery (CR or CRi)
Secondary	Determine the proportion of subjects remaining in complete remission (CR +CRi) at 6 months, at 12 months and at 18 months
Secondary	Determine the median duration of overall survival (OS)
Secondary	Correlate clinical responses and duration of responses with specific cytogenetic abnormalities
Secondary	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
Secondary	Define the safety profile and confirm the acceptability of amonafide and cytarabine
Secondary	Correlate PK exposure of amonafide and acetylation of amonafide with safety and efficacy assessments in individual subjects