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

Phase 2

Recruiting

• Conditions: APL
• Interventions: Drug: Chidamide+venetoclax

• Registration Number: NCT05881265
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief Summary

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.

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 Timeline

• Study Start: 2023-05-15
• Study First Submitted: 2023-05-16
• Study First Submitted QC: 2023-05-30
• Study First Posted: 2023-05-31
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-14
• Last Update Posted: 2025-02-18
• Primary Completion: 2026-01-01
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Chi-Ven treatment	Chidamide+venetoclax	Patients receive chidamide and venetoclax treatment

Primary Outcome Measures

Name	Time	Method
complete remission and complete remission with incomplete recovery of peripheral blood count	Day 42	patients with \<5% promyelocytes in bone marrow with or without full recovery of peripheral cell count

Secondary Outcome Measures

Name	Time	Method
Non-relapse mortality	1 year	Patients died without documentation of leukemia relapse
Early death	42 days	Patients died of any causes
Overall survival	1 year	Patients alive
Leukemia-free survival	1 year	Patients alive without leukemia relapse
relapse	1 year	Patients with documentation of leukemia relapse

Trial Locations

Locations (5)

Zhaxin Hospital, Go Broad Health Care; 🇨🇳 Shanghai, Shanghai, China

Jiong HU; 🇨🇳 Shanghai, Shanghai, China

The Affiliated Huai An No 1 Perople's Hospital of NanJing University; 🇨🇳 Huai'an, Jiangsu, China

The First Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

NanFang Hospital; 🇨🇳 Guangzhou, China