Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

PRIMARY OBJECTIVES: I. To establish the recommended phase II dose of 5-azacytidine (azacitidine) when combined with high-dose cytarabine (HiDAC) and mitoxantrone (mitoxantrone hydrochloride) chemotherapy in high-risk acute myeloid leukemia (AML) patients. SECONDARY OBJECTIVES: I. To determine the complete remission (CR) rate following the use of induction chemotherapy regimen of 5-azacytidine followed by high-dose cytarabine (HiDAC) and mitoxantrone chemotherapy in high-risk AML patients. II. To determine the toxicity of the combination regimen. III. To determine the disease-free survival (DFS) and overall survival (OS) of the patient population. IV. To determine the gene expression levels of topoisomerase II and deoxycytidine kinase in leukemia blasts pre-treatment and following therapy with 5-azacytidine. V. To collect specimens for banking for use in future research studies with a view to elucidating the predictors of response to epigenetic therapies. OUTLINE: This is a dose-escalation study of azacitidine. INDUCTION: Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) once daily (QD) on days 1-5, cytarabine IV over 4 hours on days 6 and 10, and mitoxantrone hydrochloride IV over 60 minutes on days 6 and 10. CONSOLIDATION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients ineligible for allogeneic stem cell transplantation continue on to maintenance. MAINTENANCE: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.