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)

Study start date: June 6, 2012

Inclusion Criteria: Patients must have one of the following disease characteristics: Therapy-related myeloid neoplasm (t-MN) age >= 18 years Patients must have received cytotoxic chemotherapy, radiation, or a drug known to affect the properties of deoxyribonucleic acid (DNA) or cell growth, prior to current diagnosis of therapy-related myeloid neoplasm (t-MN); this broad definition is meant to include any prior therapy with chemicals that affect DNA replication, DNA integrity, or DNA structure, or chemicals that alter cell growth; this includes traditional cytotoxic chemotherapy, newer immunologic agents that have been shown to have cytotoxic activities in addition to immunosuppressive functions, and other chemicals; note that patients with primary AML could be diagnosed with a t- MN if morphology/cytogenetic analysis clearly indicated that the second process is not a relapse of the original disease AML arising from an antecedent hematological disorder age >= 18 years De novo AML in patients age >= 60 years Relapsed and/or refractory AML >= 18 years Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment Male and female patients must use an effective contraceptive method during the study and for at least 6 months after study treatment Patients must be at least 2 weeks from major surgery, radiation therapy, participation in other investigational trials and must have recovered from clinically significant toxicities of these prior treatments Ability to understand and willingness to sign the informed consent form Exclusion Criteria: Concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in this protocol Diagnosis of acute promyelocytic leukemia (APL) Use of investigational agents/any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea (note: for patients with hyperleukocytosis [white blood cell (WBC) > 20,000/uL], hydroxyurea [and leukapheresis, if clinically indicated] will be initiated and these patients will receive 5-azacytidine when the WBC count has decreased to =< 20,000/uL; hydroxyurea can be overlapped with 5-azacytidine in selected cases, after consultation with the study chair; hydroxyurea must be discontinued before the initiation of the HiDAC/mitoxantrone chemotherapy) Prior treatment with 5-azacytidine followed immediately by HiDAC and mitoxantrone as proposed in this study (note: prior therapy with 5-azacytidine or decitabine or HiDAC or mitoxantrone would be allowed-in patients with relapsed/refractory disease- unless the prior therapy was identical to the schema/schedule proposed in this study) Active second cancer other than specified; active cancer refers to cancer that requires systemic chemotherapy or biological therapy within 6 months of the study entry; patients who have received only hormonal therapy in the neoadjuvant or adjuvant setting in the past 6 months may participate in this study Have any other severe concurrent disease, or have a history of serious organ dysfunction (e.g. uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, infection, psychiatric illness) that may in the judgment of the treating physician/ principal investigator place the patient at undue risk to undergo treatment Pregnant or lactating patients Any significant concurrent illness that would, in the judgment of the treating physician/principal investigator, compromise patient safety or compliance, or study participation