APL
Conditions
Keywords
refractory，APL
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.
Interventions
DRUGChidamide+venetoclax
Chidamide 30mg BIW x 4 weeks; Venetoclax 100mg D1, 200mg D2 and 400mg D3-28
Sponsors
Shanghai Clinical Research Center
Shanghai Jiao Tong University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Chi-Ven treatment
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
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）
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China
Contacts
Primary ContactChun Wang, M.D.,
Outcome results
None listed