Clinical trial NCT05881265: Treatment of Chidamide and Venetoclax for Retinoic Acid and Arsenic Resistant Acute Promyelocytic Leukemia
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: APL
Keywords: refractory，APL
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Shanghai Clinical Research Center
First posted: 2023-05-31
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Chi-Ven treatment
Primary purpose: TREATMENT

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.

Eligibility criteria: 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）

Primary outcomes:
measure: complete remission and complete remission with incomplete recovery of peripheral blood count
timeFrame: Day 42
Secondary outcomes:
measure: Overall survival
timeFrame: 1 year
measure: Leukemia-free survival
timeFrame: 1 year
measure: Non-relapse mortality
timeFrame: 1 year
measure: relapse
timeFrame: 1 year
measure: Early death
timeFrame: 42 days
Other outcomes:
Locations:
city: Huai'an
country: China
facility: The Affiliated Huai An No 1 Perople's Hospital of NanJing University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shanghai
country: China
facility: Jiong HU
state: Shanghai
city: Shanghai
country: China
facility: Zhaxin Hospital, Go Broad Health Care
state: Shanghai
city: Guangzhou
country: China
facility: NanFang Hospital
Study officials:
affiliation: Zhaxin Hospital, Go Broad Health Care
name: Chun Wang
role: STUDY_DIRECTOR
References: