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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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APL

Intervention / Treatment
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* Drug: Chidamide+venetoclax


Participation Criteria
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Eligibility Criteria
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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）

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Chi-Ven treatment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission and complete remission with incomplete recovery of peripheral blood count | 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 | Patients alive | 1 year | 
| Leukemia-free survival | Patients alive without leukemia relapse | 1 year | 
| Non-relapse mortality | Patients died without documentation of leukemia relapse | 1 year | 
| relapse | Patients with documentation of leukemia relapse | 1 year | 
| Early death | Patients died of any causes | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory，APL