Decitabine Followed by Mitoxantrone Hydrochloride, Etoposide, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

PRIMARY OBJECTIVES: I. Estimate the maximum tolerated dose (MTD) of decitabine priming followed by sequential mitoxantrone hydrochloride/etoposide/cytarabine (MEC) chemotherapy in adults with relapsed/refractory acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. Determine, within the limits of a Phase 1/2 study, disease response and duration of remission. II. Identify biomarkers (e.g., deoxyribonucleic acid \[DNA\] methylation and/or gene expression changes) associated with treatment responses. OUTLINE: This is a phase I, dose-escalation study of decitabine followed by a phase II study. Patients receive decitabine intravenously (IV) on days -9 to -5 (dose level 1), days -11 to -5 (dose level 2), or days -14 to -5 (dose level 3). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving complete response (CR) or CR with incomplete platelet count recovery (CRp) may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. After completion of study treatment, patients are followed up every 3 months for up to 5 years.