Ignite Creation Date:
2025-12-24 @ 9:54 PM
Ignite Modification Date:
2025-12-25 @ 7:32 PM
Study NCT ID:
NCT05627232
Status:
SUSPENDED
Last Update Posted:
2025-11-03
First Post:
2022-11-16
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Tazemetostat and Palbociclib With CPX-351for R/R AML
Sponsor:
Thomas Jefferson University
Organization:
Study Overview
Official Title:
A Two-Part Phase 1b Study Evaluating the Combination of Tazemetostat and CPX-351 (Part 1) and Tazemetostat and CPX-351 Following Pre-Treatment With Palbociclib (Part 2) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
Status:
SUSPENDED
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Cohort Closed
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: