Pinometostat With Standard Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia and MLL Gene Rearrangement

PRIMARY OBJECTIVES: I. Determine a safe and tolerable schedule of pinometostat continuous intravenous infusion in combination with daunorubicin hydrochloride (daunorubicin) and cytarabine in patients with untreated, newly diagnosed acute myeloid leukemia harboring MLL rearrangement. II. Determine the rate of complete remission (complete remission \[CR\], CR with incomplete hematologic recovery \[CRi\]) in patients with newly diagnosed acute myeloid leukemia harboring MLL rearrangement after treatment with pinometostat in combination with daunorubicin and cytarabine. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. Estimate biologic activity of 7 day window treatment of pinometostat monotherapy. III. Estimate the toxicity profile of pinometostat alone (week 1) and in combination with daunorubicin and cytarabine. IV. Estimate event free and overall survival of patients with MLL rearranged acute myeloid leukemia after combination treatment with pinometostat, daunorubicin, and cytarabine. V. Estimate the early death rate (death =\< 30 days) of pinometostat, daunorubicin, and cytarabine. VI. Determine the rate of minimal residual disease (MRD) negativity by clinical flow cytometry on post-treatment recovery bone marrow. OUTLINE: This is a phase I, dose-escalation study of pinometostat followed by a phase II study. Patients are assigned to 1 of 2 cohorts. COHORT I: Patients receive higher dose pinometostat intravenously (IV) continuously on days 1-7 and lower dose pinometostrat IV continuously on days 8-35. Patients also receive daunorubicin hydrochloride IV over 10-30 minutes on days 8-10 and cytarabine IV continuously on days 8-14. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients who do not achieve CR/CRi after treatment receive pinometostat IV continuously on days 1-28, daunorubicin hydrochloride IV over 10-30 minutes on days 1 and 2 and cytarabine IV continuously on days 1-5 in the absence of disease progression or unacceptable toxicity. COHORT II: Patients receive higher dose pinometostat IV continuously on days 1-35. Patients also receive daunorubicin hydrochloride IV over 10-30 minutes on days 8-10 and cytarabine IV continuously on days 8-14. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients who do not achieve CR/CRi after treatment receive pinometostat IV continuously on days 1-28, daunorubicin hydrochloride IV over 10-30 minutes on days 1 and 2 and cytarabine IV continuously on days 1-5 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up monthly for 1 year, then every 3 months for up to 4 years.