Treatment of Chidamide and Venetoclax for Retinoic Acid and Arsenic Resistant Acute Promyelocytic Leukemia

February 14, 2025 updated by: Jiong HU, Shanghai Jiao Tong University School of Medicine

Multi-center Phase II Prospective Study for the Treatment of Chidamide and Venetoclax in Patients With All-trans Retinoic Acid (ATRA) and Arsenic (As) Resistant Acute Promyelocytic Leukemia (APL)

Based on the current treatment with retinoic acid (ATRA) and arsenic (As), most patients with APL achieved long-term survival. There are few patients relapsed and became refractory to the RA and As treatment. In our pre-clinical study, we found that targeting histone deacetylase inhibitor 3 (HDAC3)degraded PML-RARa oncoprotein and induced differentiation and apoptosis of RA and As resistant APL in vitro and in vivo. In this study, we evaluate the efficacy and feasibility of combination therapy for HDAC3 inhibitor and venetoclax in patients with refractory APL.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

For patients with newly-diagnosed acute promyelocytic leukemia (APL), the combination therapy retinoic acid (ATRA) combined with arsenic (As) is the mainstay upfront treatment. Most patients enjoy long-term survival with or without chemotherapy. Even though with such good prognosis, there are still some patients relapsed and eventually became refractory to RA and As treatment. In our pre-clinical study, we demonstrate that targeting histone deacetylase inhibitor 3 (HDAC3) could degrade PML-RARa oncoprotein and induce differentiation and apoptosis of RA and As resistant APL in vitro and in vivo. In this multi-center prospective study, we evaluate the efficacy and feasibility of combination therapy for HDAC3 inhibitor (chidamide) and venetoclax in patients with refractory APL.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Guangzhou, China
        • Recruiting
        • Nanfang Hospital
        • Contact:
    • Jiangsu
      • Huai'an, Jiangsu, China
        • Not yet recruiting
        • The Affiliated Huai An No 1 Perople's Hospital of NanJing University
        • Contact:
    • Jiangxi
      • Nanchang, Jiangxi, China
        • Not yet recruiting
        • The First Affiliated Hospital of Nanchang University
        • Contact:
          • Wenhua Zhou
    • Shanghai
      • Shanghai, Shanghai, China, 200025
        • Recruiting
        • Jiong HU
        • Contact:
        • Contact:
      • Shanghai, Shanghai, China
        • Active, not recruiting
        • Zhaxin Hospital, Go Broad Health Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with PML-RARα+ APL
  • Patients in non-remission status after treatment of RA combined with As
  • Patients with life expectance >=3 months
  • Inform consent provided

Exclusion Criteria:

  • Patients with incontrollable infection
  • Patients with life-expectancy less than 2 months
  • Patients with abnormal liver (>3XN) and renal function (>3XN）

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Chi-Ven treatment
Patients receive chidamide and venetoclax treatment
Drug: Chidamide+venetoclax
Chidamide 30mg BIW x 4 weeks; Venetoclax 100mg D1, 200mg D2 and 400mg D3-28
Other Names:
  • Chi-VEN

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
complete remission and complete remission with incomplete recovery of peripheral blood count
Time Frame: Day 42
patients with <5% promyelocytes in bone marrow with or without full recovery of peripheral cell count
Day 42

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 1 year
Patients alive
1 year
Leukemia-free survival
Time Frame: 1 year
Patients alive without leukemia relapse
1 year
Non-relapse mortality
Time Frame: 1 year
Patients died without documentation of leukemia relapse
1 year
relapse
Time Frame: 1 year
Patients with documentation of leukemia relapse
1 year
Early death
Time Frame: 42 days
Patients died of any causes
42 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Jiao Tong University School of Medicine

Collaborators

Shanghai Clinical Research Center

Investigators

  • Study Director: Chun Wang, Zhaxin Hospital, Go Broad Health Care

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2023

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

May 16, 2023

First Submitted That Met QC Criteria

May 30, 2023

First Posted (Actual)

May 31, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 14, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R/R-APL-2023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data is available only based on request to study director or principle investigator

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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