Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDE Study

Inclusion Criteria:

• Diagnosis of AML according to WHO diagnostic criteria (at least 20% blasts in theperipheral blood or bone marrow), with FAB classification other than M3 (AcutePromyelocytic Leukemia), documented by bone marrow aspiration and biopsy performedwithin 14 days prior to administration of 1st dose of remission inductionchemotherapy;

• Either: Known and documented exposure to specific leukemogenic therapy of a specifiednature for a non-myeloid condition; OR Documented diagnosis of MDS according to WHOcriteria for at least 3 months prior to study entry, with prior bone marrow aspirate,biopsy and peripheral blood smear documenting MDS available to be submitted forsubsequent central pathology review.

• Age 18 years or older;

• Eastern Cooperative Oncology Group (ECOG) performance score =< 2;

• Fertile sexually active patients (men and women) must use an effective method ofcontraception which must be continued throughout the study.

• Women of childbearing potential must have a negative serum pregnancy test.

• Left Ventricular Ejection Fraction (LVEF) >= 50%, as determined by multiple-gatedacquisition scan (MUGA) or echocardiogram (ECHO) within 14 days prior toadministration of 1st dose of remission induction chemotherapy;

• Adequate renal function as evidenced by the following laboratory test, obtained within 10 days prior to administration of 1st dose of remission induction chemotherapy: Serumcreatinine =< 1.5 x ULN;

• Adequate hepatic function as evidenced by the following laboratory tests, obtainedwithin 10 days prior to administration of 1st dose of remission induction chemotherapy (unless attributed to hepatic involvement with AML): Total serum bilirubin =< 1.5 xULN;Serum AST and ALT =< 1.5 x ULN;

• Ability of the patient to participate fully in all aspects of this clinical trial;

• Written Informed Consent and HIPAA authorization (USA sites only) must be obtained anddocumented.

Exclusion Criteria:

• Histologic diagnosis of FAB M3 Acute Promyelocytic Leukemia;

• Clinically active CNS leukemia;

• Prior induction therapy for AML;

• Known HIV positive;

• Known active hepatitis B or C, or any other active liver disease;

• Patients with parenchymal abnormality on screening chest x-ray must have no evidenceof pulmonary infection on chest tomography (CT) prior to starting remission inductiontherapy.

• Any major surgery or radiation therapy within 4 weeks prior to study entry;

• Prior cytotoxic chemotherapy for MDS within 4 weeks prior to study entry (patientswith rapidly rising blast count may be enrolled within 4 weeks of prior cytotoxicchemotherapy with waiver from the Medical Monitor);

• Persistent chronic non-hematologic toxicity (other than alopecia) greater than grade 1from prior therapy for MDS;

• Serious concomitant illnesses (for example, pulmonary infiltrate, unstable angina ormyocardial infarction or stroke within 3 months prior to study entry, congestive heartfailure AHA class 2 or greater, uncontrolled hypertension, uncontrolled diabetes,actively bleeding gastric ulcer, etc.), which in the investigator's opinion would notmake the patient a good candidate for the trial;

• Pregnant or breast feeding;

• History of clinically significant allergic reactions attributed to compounds ofsimilar chemical or biological composition to amonafide, cytarabine or daunorubicin;

• Prior enrollment in this trial;

• Any other known condition (e.g., familial, sociological, or geographical) or behavior (including substance dependence or abuse, psychological or psychiatric illness), whichin the investigator's opinion would make the patient a poor candidate for the trial.