NCT05627232

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

A Two-Part Phase 1b Study Evaluating the Combination of Tazemetostat and CPX-351 (Part 1) and Palbociclib Pre-Treatment Followed by CPX-351 (Part 2) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Thomas Jefferson University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a two-part phase Ib dose escalation study to evaluate the safety and preliminary efficacy of the combination of tazemetostat and CPX-351 (Part 1) and of pre-treatment with palbociclib followed by CPX-351 (Part 2) for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). Part 1 of the study will seek to establish the safety, tolerability, biological activity and recommended dose for further evaluation (RDFE) of tazemetostat in combination with standard-dose CPX-351. Part 2 of the study will seek to establish the safety, tolerability, biological activity RDFE of pre-treatment palbociclib prior CPX-351.

Detailed description

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.

Conditions

• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Tazemetostat	Given PO
DRUG	Liposome-encapsulated Daunorubicin-Cytarabine	Given IV
PROCEDURE	Bone Marrow Aspiration and Biopsy	Undergo bone marrow aspiration and biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Palbociclib	Given PO

Timeline

• Start date: 2023-08-28
• Primary completion: 2028-01-01
• Completion: 2029-01-01
• First posted: 2022-11-25
• Last updated: 2026-03-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study