Tazemetostat and Palbociclib With CPX-351for R/R AML

PRIMARY OBJECTIVE: Part 1: To determine the RDFE of tazemetostat in combination with CPX-351 in patients with R/R-AML. Part 2: To determine the RDFE of palbociclib pre-treatment prior to CPX-351 in patients with R/R-AML. SECONDARY OBJECTIVE: I. To evaluate the preliminary efficacy of tazemetostat in combination with CPX-351 (Part 1) and of palbociclib pre-treatment followed by CPX-351 (Part 2). EXPLORATORY OBJECTIVES: 1. To determine whether treatment with the EZH2 inhibitor tazemetostat de-condenses the H3K27me3-marked chromatin of AML blasts. 2. To determine whether cell cycle re-entry of AML cells after palbociclib treatment influences DNA damage and apoptosis induced by combining EZH2 inhibition with anthracycline-based therapy This is a phase 1b, single-institution, two-part, dose-escalation study utilizing tazemetostat in combination with CPX-351 (Part 1) and palbociclib pre-treatment followed by CPX-351 (Part 2) for patients with R/R-AML who are fit to receive intensive chemotherapy. The study will take place in two parts: Part 1: Dose escalation via traditional 3+3 design of tazemetostat in combination with CPX-351 . Part 2: Dose escalation via traditional 3+3 design of palbociclib pre-treatment followed by tazemetostat/CPX-351combination. Once the RDFE of tazemetostat in combination with CPX-351 and the RDFE of palbociclib pre-treatment followed by CPX-351 have been determined, we hope to pursue further evaluation of the safety and preliminary efficacy of the three-drug combination pending further protocol amendment.. After completion of study treatment, patients are followed up at 3 months, 6 months, and 1 year for clinical outcomes including survival.