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

NCT ID: NCT05627232

Last Updated: 2025-11-03

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-28
• Study Completion Date: 2026-01-31

Brief 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 following pre-treatment with palbociclib 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 Part 2 dose of tazemetostat in combination with standard-dose CPX-351. Once the recommended Part 2 dose is established, the study will proceed to Part 2 where pre-treatment with palbociclib will be administered prior to the tazemetostat/CPX-351 dose combination. The objective of Part 2 is to establish the optimal dose of palbociclib.).

Detailed Description

PRIMARY OBJECTIVE:

Part 1: To determine the optimal dose of tazemetostat in combination with CPX-351 in patients with R/R-AML.

Part 2: To determine the optimal dose of palbociclib pre-treatment prior to combination of tazemetostat/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 Tazemetostat and Palbociclib with CPX-351for R/R AML pre-treatment prior to tazemetostat/CPX-351 combination (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 1, single-institution, two-part, dose-escalation study utilizing tazemetostat in combination with CPX-351 (Part 1) and palbociclib pre-treatment followed by tazemetostat/CPX-351 combination (Part 2) for patients with relapsed or refractory 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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part I (tazemetostat, CPX-351)

Patients receive tazemetostat PO BID on days -1 to 6, 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.

Group Type: EXPERIMENTAL

Tazemetostat

Intervention Type: DRUG

Given PO

Liposome-encapsulated Daunorubicin-Cytarabine

Intervention Type: DRUG

Given IV

Bone Marrow Aspiration and Biopsy

Intervention Type: PROCEDURE

Undergo bone marrow aspiration and biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Part II: palbociclib Pre-Treatment Followed by Tazemetostat + CPX-351

Patients receive palbociclib PO QD on days -3 to -1, then tazemetostat PO twice daily (Days -1 to 6), 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.

Group Type: EXPERIMENTAL

Tazemetostat

Intervention Type: DRUG

Given PO

Liposome-encapsulated Daunorubicin-Cytarabine

Intervention Type: DRUG

Given IV

Bone Marrow Aspiration and Biopsy

Intervention Type: PROCEDURE

Undergo bone marrow aspiration and biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Palbociclib

Intervention Type: DRUG

Given PO

Interventions

Tazemetostat

Given PO

Intervention Type: DRUG

Liposome-encapsulated Daunorubicin-Cytarabine

Given IV

Intervention Type: DRUG

Bone Marrow Aspiration and Biopsy

Undergo bone marrow aspiration and biopsy

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Palbociclib

Given PO

Intervention Type: DRUG

Other Intervention Names

1403254-99-8; E7438; EPZ-6438; EPZ6438; N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(oxan-4-yl)amino)-4-methyl-4'-((morpholin-4-yl)methyl)(1,1'-biphenyl)-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide; CPX-351; Cytarabine-Daunorubicin Liposome for Injection; Daunorubicin and Cytarabine (Liposomal); Liposomal AraC-Daunorubicin CPX-351; Liposomal Cytarabine-Daunorubicin; Liposome-encapsulated Combination of Daunorubicin and Cytarabine; Vyxeos; Biological Sample Collection; Biospecimen Collected; Specimen Collection; 571190-30-2; 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one; Ibrance; PD 0332991; PD 332991; PD 991; PD-0332991; Pyrido(2,3-d)pyrimidin-7(8H)-one; 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(1-piperazinyl)-2-pyridinyl)amino)-

Eligibility Criteria

Inclusion Criteria

• Provide signed and dated informed consent form
• Willing to comply with all study procedures and be available for the duration of the study
• Male or female >= 18 years of age
• Histologically confirmed acute myeloid leukemia (non-M3) relapsed from or refractory to at least 1 prior line of therapy. Bone marrow aspirate and biopsy within 28 days of screening is acceptable. If no prior bone marrow biopsy is available, bone marrow biopsy must be performed during screening unless:

• If the subject has >= 20% myeloblasts present in the peripheral blood, a bone marrow biopsy is not necessary to meet this criterion
• Treatment with a prior investigational agent is acceptable so long as it has not been administered within 2 weeks of enrollment and any prior adverse effects have resolved to grade 1 or less with the exception of alopecia
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Life expectancy of at least 4 weeks
• Must be able to consume oral medication
• Subjects must have recovered from the toxic effect of any prior therapy to =< grade 1 (except alopecia)
• Creatine clearance (CrCL) >= 45
• Total bilirubin < 2 x upper limit of normal (ULN)
• Female subjects of childbearing age must have a negative pregnancy test

Exclusion Criteria

• Subjects with acute promyelocytic leukemia
• Subjects receiving any active chemotherapy agents (except hydroxyurea). Intrathecal methotrexate and cytarabine are permissible
• Subjects whose participation would result in a total cumulative dose of daunorubicin greater than 550 mg/m^2 or greater than 450 mg/m^2 if they previously received mediastinal radiation
• Subjects with evidence of active central nervous system (CNS) leukemia involvement. Lumbar puncture is not required for enrollment in the absence of neurologic symptoms
• Subjects must not be receiving growth factors (except erythropoietin)
• Subjects with currently active second malignancy with the exception of nonmelanoma skin cancer, carcinoma in situ of the cervix, resected prostate cancer with Gleason score =< 6
• Subjects with unstable cardiac disease or uncontrolled arrhythmia
• Subjects with other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate to receive high-intensity therapy
• Subjects who are pregnant or breastfeeding
• Subjects with known allergic reactions to components of the study product(s)
• Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pennsylvania Department of Health

OTHER_GOV

Sponsor Role: collaborator

Thomas Jefferson University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gina Keiffer, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

JT 24252

Identifier Type: OTHER

Identifier Source: secondary_id

4100095617

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

22G.769

Identifier Type: -

Identifier Source: org_study_id