A Phase I Study of Azacitidine Combined With Mitoxantrone and Etoposide (A-NOVE) Chemotherapy for Patients Age >/= 60 With Poor Prognosis Acute Myeloid Leukemia (AML)
I. To determine the highest tolerated dose of two dosing schedules of azacitidine when
combined with mitoxantrone and etoposide (A-NOVE) chemotherapy in poor prognosis older
patients with acute myeloid leukemia (AML).
II. To evaluate the toxicity of this regimen.
I. To determine the complete response (CR) rate and using this regimen. II. To evaluate
changes in topisomerase II activity, DNA methylation and DNA expression arrays in leukemia
cells during azacitidine treatment, and to correlate these changes with responses to A-NOVE
III. To evaluate relapse-free survival (RFS) and overall survival (OS) in patients receiving
post-remission consolidation with A-NOVE in patients achieving CR.
OUTLINE: This is a multicenter, phase I dose-escalation study of azacitidine.
Patients receive induction therapy comprising azacitidine subcutaneously (SC) once daily on
days 1-7, mitoxantrone hydrochloride IV over 30 minutes, and etoposide IV over 1 hour on
days 4-8. Patients may receive up to 2 additional courses of the same treatment as
re-induction or consolidation therapy. Blood and bone marrow samples may be collected on
days 0 and 4 for laboratory correlative studies.
After completion of study treatment, patients are followed up periodically.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose of azacitidine that can be safely combined with mitoxantrone hydrochloride and etoposide chemotherapy
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Up to 2 courses of treatment
University Health Network-Princess Margaret Hospital
United States: Food and Drug Administration