This study aims to evaluate the safety and efficacy of homoharringtonine combined with venetoclax and azacitidine regimen (HVA) in newly diagnosed MPAL patients, providing a basis for the use of the HVA regimen in the treatment of MPAL.
Our preliminary studies show that MPAL not only highly expresses BCL-2, but also highly expresses MCL-1, suggesting the need to explore combining MCL-1 inhibitors on the basis of Ven and HMAs. Our preliminary research confirmed that homoharringtonine (HHT) significantly enhances the anti-leukemia effect of Ven/AZA via inhibition of MCL-1. Originally, we designed the HVA regimen by combining HHT with Ven/AZA for the treatment of AML, and achieved better efficacy and safety. Then we exploratively treated 11 MPAL patients with HVA regimen and acquired promising response and safety. In this study, we conduct a multicenter, prospective, single arm trial to evaluate the efficacy and safety of HVA in the treatment of newly diagnosed MPAL.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
HVA regimen: Venetoclax: 100 mg on day 1, 200 mg on Day 2, 400 mg per day from Day 3 to Day 14; Azacitidine: 75 mg/m2 per day by subcutaneous injection from Day 1 to Day 7; Homoharringtonine : 1mg/m2 per day by intravenous infusion from Day 1 to Day 7. If co-administered with CYP3A inhibitors, the dose of venetoclax was adjusted in accordance with prescribing recommendations. Fms-related receptor tyrosine kinase 3 (FLT3) inhibitors were recommended in patients with FLT3-ITD/TKD mutations. Also tyrosine kinase inhibitors were recommended in patients with BCR/ABL-positive.
Department of Hematology, Guangdong Second Provincial General Hospital
Guangzhou, Guangdong, China
Composite Complete Remission (CRc)
The rate of composite complete remission including complete remission (CR) and CR with incomplete blood count recovery (CRi)
Time frame: At the end of cycle 2 (28 days for a cycle)
Complete remission (CR)
Camplete remission is defined as BM with\>5% blasts and wthout extramedullary infltration and recovery of peripheral blood cells.
Time frame: At the end of cycle 2 (28 days for a cycle)
Overall response rate (ORR)
ORR includes CRc, partial response (PR), and morphologic leukemia-free state(MLFS).
Time frame: At the end of cycle 2 (28 days for a cycle)
Rate of Measurable residual disease (MRD) negative
MRD is monitored using flow cytometric analysis with a positive MRD threshold of 0.1%.
Time frame: At the end of cycle 2 (28 days for a cycle)
Adverse events
Adverse events including hematologic and nonhematologic toxicities in the treatment of HVA regimen
Time frame: At the end of cycle 2 (28 days for a cycle)
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