The aim of this study is to evaluate the safety and efficacy of homohartonine combined with venetoclax and azacitidine (HVA) versus intensive chemotherapy (IA/DA) or venetoclax combined with azacitidine (VA) in newly diagnosed high-risk AML patients.
The HVA regimen exerts a synergistic pro-apoptotic effect and has demonstrated significant clinical efficacy against R/R AML and also overcomes adaptive resistance observed in the VA regimen. Exploratory work with small sample sizes in first-line settings suggests that combination of HHT and Ven+AZA exhibits potent anti-AML effects with good safety profiles, particularly in overcoming the impact of high-risk factors associated with AML relative to standard treatments. This indicates its potential as a more ideal option for the treatment of newly diagnosed AML with high risk factors. Therefore a prospective, multi-center, randomized controlled clinical study is planned to evaluate the efficacy and safety of the HVA regimen compared to intensive chemotherapy (IA/DA) or Venetoclax plus azacitidine (VA) regimens in newly diagnosed high-risk fit-AML or unfit AML patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
876
Homoharringtonine (HHT) is given by venous drip daily at 1 mg/m2 from day 1 to 7. Venetoclax (VEN) is given 100 mg on day 1, 200 mg on day 2, and 400 mg orally from day 3 to day 14. Azacitidine (AZA) is given 75 mg/m2 subcutaneously from day 1 to 7.
VEN is given 100 mg on day 1, 200 mg on day 2, and 400 mg orally from day 3 to day 28, and AZA (75 mg/m2) is given subcutaneously from day 1 to 7.
Standard Chemotherapy includes IA(Idarubicin combined with Cytarabine) or DA(Daunorubicin combined with Cytarabine). IDA is given by venous drip daily at 12mg/m2, or DNR is given by venous drip daily at 60mg/m2, from day 1-3, combined with Ara-C at 100mg/m2 by continuously venous drip from day 1-7.
Department of Hematology,Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, China
RECRUITINGComposite complete remission (CRc)
CRc includes complete remission (CR) and complete remission accompanied with with incomplete count recovery (CRi).
Time frame: At the end of cycle 2 (each cycle is 28 days).
Complete remission (CR)
Complete remission is defined as BM with \>5% blasts and without extramedullary infltration and recovery of peripheral blood cells.
Time frame: At the end of cycle 2 (each cycle is 28 days).
Overall response rate (ORR)
ORR includes CRc, partial response (PR), and morphologic leukemia-free state (MLFS).
Time frame: At the end of cycle 2 (each cycle is 28 days).
DOR
duration of response
Time frame: 1 year
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 (each cycle is 28 days).
Overall survival (OS)
OS is calculated from enrollment to death or the last follow-up.
Time frame: 1 year
Event-free survival (EFS)
EFS is calculated from enrollment to the date of relapse or death or the last follow-up.
Time frame: 1 year
Adverse events (AE)
AE are recorded from the first dose until 28 days after treatment discontinuation and are graded according to the NCI Common Terminology Criteria for Adverse Events version 5.0.
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Time frame: The first dose until 28 days after treatment discontinuation