A Phase II Study of the Aurora A Kinase Inhibitor Alisertib in Combination With 7+3 Induction Chemotherapy in Patients With High-risk Acute Myeloid Leukemia
This research study is studying a targeted therapy (a form of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells) as a possible treatment for high-risk acute myeloid leukemia. The names of the study interventions involved in this study are: * Alisertib / MLN8237 * Cytarabine / Cytosine Arabinoside * Idarubicin / Idarubicin hydrochloride * Daunorubicin (Can be used in place of idarubicin)
• Participants must have pathologically confirmed, newly diagnosed high-risk acute myeloid leukemia, as defined by at least one of the following criteria
‣ Age greater than or equal to 65 years
⁃ Poor risk karyotype, as per Leukemianet criteria
⁃ Antecedent or underlying myelodysplastic syndrome or myeloproliferative neoplasm
⁃ AML with MDS-related changes
• Adults, age 18 years or older at the time of diagnosis, eligible for standard induction chemotherapy according to their treating physician.
• ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A)
• Left ventricular ejection fraction \> 50% as measured by echocardiogram or MUGA scan
• Must not have received systemic antineoplastic therapy including radiation therapy within 14 days of the study enrollment, except hydroxyurea or 6-mercaptopurine for the purposes of cytoreduction. Patients may also have received all-trans retinoic acid (ATRA) if there is an early suspicion of acute promyelocytic leukemia (APL, M3-AML), although if confirmed to have APL these patients will be excluded from the study.
• Adequate renal function as defined by: calculated creatinine clearance ≥40 mL/min (Cockcroft-Gualt Formula)
• Direct bilirubin \< 2.0 x upper limit of normal (ULN), SGOT (AST) and SGPT (ALT)\< 2.5 x ULN. AST and/or ALT may be up to 5X ULN if thought to be secondary to leukemia.
• The effects of alisertib on the developing human fetus are unknown. For this reason and because other chemotherapeutic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation, and 6 months after completion of therapy.
• Subject must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after alisertib administration.
• Ability to understand and the willingness to sign a written informed consent document.