This study aims to compare the efficacy and safety of a shortened treatment course based on the bone marrow blast count on Day 14 versus standard treatment in patients with acute myeloid leukemia treated with venetoclax plus azacitidine.
The standard 28-day cycle of venetoclax is widely recommended for the first cycle of venetoclax plus azacitidine induction therapy in patients with acute myeloid leukemia (AML). However, it has been found that the 28-day treatment cycle was not tolerant for some patients due to severe myelosuppression and infection, which may lead to treatment interruption and delays in subsequent treatment cycles. This is a multicenter, randomized controlled, open-label, non-inferiority study, which compare the efficacy and safety of a shortened treatment course based on the bone marrow blast count on Day 14 versus standard treatment in AML patients treated with venetoclax plus azacitidine induction therapy. This study plans to enroll 250 newly diagnosed AML patients who are intolerant to intensive chemotherapy regimens. Enrolled subjects will be assigned to either the optimized treatment group or the standard treatment group in a 1:1 ratio with stratified blocked randomization, with ELN 2022 classification as the stratification factor. In the optimized treatment group, if the bone marrow blast count is \<5% on Day 14 of the first induction, the duration of venetoclax will be shortened to 14 days; otherwise, the 28-day course will be completed as scheduled. In the standard treatment group, no bone marrow assessment will be performed on Day 14, and all patients will complete the 28-day treatment course. The duration of venetoclax in the second cycle will be 28 days or 21 days (if complete remission with incomplete hematologic recovery) for the two groups. The primary endpoint is the achievement of complete remission or complete remission with incomplete hematologic recovery (CR/CRi) within 2 treatment courses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
250
Tablet
Solution for subcutaneous
Achievement of CR/CRi within 2 treatment cycles
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 28 days). If CRi, repeat 2 weeks later.
Achievement of CR within 2 treatment cycles
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 28 days). If CRi, repeat 2 weeks later.
Achievement of CR/CRi during treatment with the venetoclax plus azacitidine regimen
Time frame: At the end of Cycles 1, 2, 3, and 5 (each cycle is 28 days) of the venetoclax-azacitidine regimen, and every 2 cycles thereafter.
Achievement of MRD negativity during treatment with the venetoclax plus azacitidine regimen
Flow cytometry analysis of bone marrow specimen.
Time frame: At the end of Cycles 1, 2, 3, and 5 (each cycle is 28 days) of the venetoclax-azacitidine regimen, and every 2 cycles thereafter.
Relapse-free survival
Relapse-free survival is defined as the number of months from the first achievement of CR/CRi to disease relapse or death from any cause, whichever came first, or censored at the last follow-up.
Time frame: From the first achievement of CR/CRi to disease relapse or death from any cause, whichever came first, assessed up to 48 months.
Overall survival
Overall survival is defined as the number of months from enrollment to death from any cause, or censored at the last follow-up.
Time frame: Time from enrollment to death from any cause, assessed up to 48 months.
Adverse events
Time frame: Time from enrollment to the end of the 2nd treatment cycle (each cycle is 28 days).
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