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

Sponsor

Shanghai Jiao Tong University School of Medicine (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05881265

Collaborator

Shanghai Clinical Research Center (Other)

Enrollment

Location

Arm

31.6

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
APL	Drug: Chidamide+venetoclax	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Chi-Ven treatmentChi-Ven treatment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

May 15, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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）

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jiong HU	Shanghai	Shanghai	China	200025

Sponsors and Collaborators

Shanghai Jiao Tong University School of Medicine
Shanghai Clinical Research Center

Investigators

Study Director: Chun Wang, Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jiong HU, Head, Blood & Marrow Transplantation Center, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine

ClinicalTrials.gov Identifier:

NCT05881265

Other Study ID Numbers:

R/R-APL-2023

First Posted:

May 31, 2023

Last Update Posted:

May 31, 2023

Last Verified:

May 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Jiong HU, Head, Blood & Marrow Transplantation Center, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine

refractory，APL

Additional relevant MeSH terms:

Leukemia, Promyelocytic, Acute

Venetoclax

Study Results

No Results Posted as of May 31, 2023