Amonafide in Combination With Cytarabine in Secondary AML

Sponsor

Xanthus Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00273884

Collaborator

(none)

Enrollment

Locations

Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Amonafide L-Malate Drug: Cytarabine	Phase 2

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 Design

Study Type:

Interventional

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2005

Study Completion Date :

Apr 1, 2009

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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