Palbociclib or Tazemetostat in Combination With CPX-351 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Refractory Acute Myeloid Leukemia Clinical Trial

Official title: A Two-Part Study Evaluating the Combination of Tazemetostat and CPX-351 (Part 1) and Palbociclib With CPX-351 (Part 2) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Status Recruiting

Clinical Trial Summary

This phase I trial tests the safety, side effects, and best dose of palbociclib or 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 or tazemetostat may kill more cancer cells.

Clinical Trial Description

PRIMARY OBJECTIVE:

Part 1: To determine the maximum tolerated dose (MTD) of tazemetostat in combination with CPX-351 in patients with relapsed/refractory (R/R)-acute myeloid leukemia (AML).

Part 2: To determine the maximum tolerated dose (MTD) of palbociclib in combination with 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 CPX-351 following pre-treatment with palbociclib (part 2).

EXPLORATORY OBJECTIVES:

I. To determine whether treatment with the EZH2 inhibitor tazemetostat de-condenses the H3K27me3-marked chromatin of AML blasts.

Il. 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.

OUTLINE: This is a dose-escalation study of tazemetostat or palbociclib in combination with fixed dose CPX-351. Patients are assigned to 1 of 2 parts.

PART I: Patients receive tazemetostat orally (PO) twice a day (BID) on days -1 to 6, and CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.

PART II: Patients receive palbociclib PO daily (QD) on days -3 to -1, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.

After completion of study treatment, patients are followed up at 3 months, 6 months, and 1 year for clinical outcomes including survival. ;

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

• NCT number: NCT05627232
• Study type: Interventional
• Source: Thomas Jefferson University
• Contact: Gina Keiffer, MD
• Phone: 215-955-2929
• Email: gina.keiffer@jefferson.edu
• Status: Recruiting
• Phase: Phase 1
• Start date: August 28, 2023
• Completion date: January 2026