Phase II Trial of Alisertib With Induction Chemotherapy in High-risk AML

Inclusion Criteria

• 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.

Exclusion Criteria

• Patients will be excluded from this study if they do not otherwise fulfill criteria mentioned in bullet 3.1.1, and are found to harbor "intermediate" or "favorable" risk cytogenetics 41:
• In such patients, a sample to evaluate patient cytogenetics will be sent at the time of diagnosis per standard clinical care and the absence of favorable or intermediate-risk cytogenetics must be confirmed by Day 8. If the cytogenetic analysis reveals that the patient harbors non-poor risk cytogenetics, or if the cytogenetic results are not received prior to Day 8, the participant will be removed from the study.
• Patients with acute bilineal/biphenotypic leukemia
• Participants who have had chemotherapy or radiotherapy within 14 days prior to entering the study, except for hydroxyurea or 6-MP as noted.
• Participants who are receiving or have received any other investigational agents within 14 days of enrollment.
• Chemo-, hormono-, radio- or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug
• Persistence of clinically relevant therapy related toxicity from previous anti-cancer therapy
• Prior allogeneic bone marrow or organ transplantation
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical