Mitoxantrone, Etoposide, and Cytarabine (MEC) Following Epigenetic Priming With Decitabine in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS): A Phase 1/2 Study
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).
I. Determine, within the limits of a Phase 1/2 study, disease response and duration of
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
Patients receive decitabine intravenously (IV) over 60 minutes 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 over 30 minutes on days
1-5, etoposide IV over 1 hour on days 1-5, and cytarabine IV over 1 hour 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
After completion of study treatment, patients are followed up every 3 months for up to 5
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of decitabine defined as the highest dose in which the incidence of dose limiting toxicity (DLT) is < 33%, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Federal Government
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