Phase I Investigation of the Feasibility of Combining 5-azacytidine With Highdose Cytarabine (HiDAC) and Mitoxantrone Chemotherapy in a Sequential Manner for Remission Induction in High-risk Acute Myelogenous Leukemia (AML)
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.
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
After completion of study treatment, patients are followed up every 3 months for 2 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase II dose of azacitidine when combined with high-dose cytarabine and mitoxantrone hydrochloride, based on incidence of dose limiting toxicity (DLT) graded according to the National Cancer Institute Common Toxicity Criteria, version 4
DLT defined as any grade 4 or greater non-hematologic toxicity (except transient [less than 48 hours] nausea/vomiting, transient [less than 48 hours] liver function test derangements) or a grade 3 non-hematological toxicity lasting more than 7 days. Persistent bone marrow aplasia (in the absence of bone marrow involvement with disease) lasting more than 56 days would also be regarded as a DLT.
University of Chicago Comprehensive Cancer Center
United States: Institutional Review Board
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