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

Shanghai Jiao Tong University School of Medicine

Status and phase: Enrolling; Phase 2

Conditions: APL

Treatments: Drug: Chidamide+venetoclax

Study type: Interventional

Funder types: Other

Identifiers

NCT05881265

R/R-APL-2023

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 16 to 70 years old

Volunteers: No 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）

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Chi-Ven treatment

Experimental group

Description:

Patients receive chidamide and venetoclax treatment

Treatment:

Drug: Chidamide+venetoclax