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

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.