PRIMARY OBJECTIVE:~I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of tazemetostat in combination with anthracycline-based chemotherapy following pre-treatment with standard-dose palbociclib in patients with relapsed/refractory (R/R)-acute myeloid leukemia (AML).~SECONDARY OBJECTIVES:~I. To evaluate the safety and tolerability of tazemetostat in combination with anthracycline based chemotherapy following pre-treatment with standard-dose palbociclib in patients with R/R-AML.~II. To evaluate the preliminary efficacy of tazemetostat in combination with anthracycline based chemotherapy following pre-treatment with standard-dose palbociclib in patients with R/R-AML.~EXPLORATORY OBJECTIVE:~I. To determine whether cell cycle re-entry of AML cells after palbociclib treatment influences deoxyribonucleic acid (DNA) damage and apoptosis induced by combining EZH2 inhibition with anthracycline-based therapy.~OUTLINE: This is a dose-escalation study of tazemetostat.~Patients receive palbociclib and tazemetostat orally (PO) and liposome-encapsulated daunorubicin-cytarabine (CPX-351) intravenously (IV) on study. Patients undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
This phase I trial tests the safety, side effects, and best dose of palbociclib and tazemetostat in combination with CPX-351 in treating patients with acute myeloid leukemia (AML) that has come back (relapsed) or does not respond to treatment (refractory). CPX-351 is a combination of the chemotherapy drugs, daunorubicin and cytarabine, which is the standard of care for AML. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Palbociclib and tazemetostat are enzyme inhibitor drugs that are approved for treating certain cancers but not AML. These drugs may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CPX-351 chemotherapy with enzyme inhibitors palbociclib and tazemetostat may kill more cancer cells.