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

Phase 2
18 Years
Not Enrolling
Acute Myeloid Leukemia

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Trial Information

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

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

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

- 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.

Type of Study:


Study Design:

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

Outcome Measure:

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

Principal Investigator

Steven Allen, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

North Shore Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

August 2005

Completion Date:

April 2009

Related Keywords:

  • Acute Myeloid Leukemia
  • AML
  • Secondary AML
  • Leukemia
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



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