This is a phase II, open-label, multi-center study evaluating the efficacy and safety of sonrotoclax (SA) in combination with azacitidine (AZA) plus individualized targeted or chemotherapeutic agents in adult participants with newly diagnosed acute myeloid leukemia (AML). Eligible participants will be stratified into different treatment arms based on genetic background (FLT3/IDH1 mutation status) and fitness for intensive chemotherapy. All participants will receive sonrotoclax with dose escalation from 20 mg/day to 320 mg/day, followed by maintenance dosing, which may be temporarily held by the investigator from Day 14 to Day 28 of each 28-day cycle based on the participant's condition, combined with azacitidine 75 mg/m²/day intravenously on Days 1-7. For participants fit for intensive chemotherapy, additional anthracycline (daunorubicin 60 mg/m²/day or idarubicin 10 mg/m²/day on Days 1-3) will be administered. For participants with FLT3 mutations, gilteritinib 80 mg once daily on Days 1-14 will be added; for those with IDH1 mutations, ivosidenib 500 mg once daily on Days 1-28 will be added.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
205
For FLT3/IDH1 wild-type participants who are eligible for chemotherapy, Anthracycline: Daunorubicin (DNR) 45 mg/m² per day on Days 1-3, or Idarubicin (IDA) 6 mg/m² per day on Days 1-3.
For IDH1 mutant participants, IDH1 inhibitor (IDH1i): Ivosidenib 500 mg once daily on Days 1-28.
For FLT3 mutant participants, FLT3 inhibitor (FLT3i): Gilteritinib 80 mg once daily on Days 1-14.
For all the participants who are eligible for this trial, Sonrotoclax (SON): 20 mg/day on Day 1, 40 mg/day on Day 2, 80 mg/day on Day 3, 160 mg/day on Day 4, and 320 mg/day on Days 5-28 of a 28-day cycle; the administration of SON may be temporarily held by the investigator from Day 14 to Day 28 based on the participant's condition.
For all the participants who are eligible for this trial, Azacitidine (AZA): 75 mg/m² per day on Days 1-7.
For FLT3-ITD mutant participants, FLT3 inhibitor (FLT3i): Quizartinib Dihydrochloride 40 mg once daily on Days 1-14.
Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai
Shanghai, Shanghai Municipality, China
RECRUITINGComposite Complete Remission
Time frame: At the end of 2 cycles of induction therapy with the SA+X regimen (each cycle is 28 days); at the end of 4 cycles of induction therapy with the SA regimen (each cycle is 28 days).
Minimal Residual Disease (MRD) Negativity Rate
Time frame: At the end of 2 cycles of induction therapy with the SA+X regimen (each cycle is 28 days); at the end of 4 cycles of induction therapy with the SA regimen (each cycle is 28 days).
Overall Response Rate
Time frame: At the end of 2 cycles of induction therapy with the SA+X regimen (each cycle is 28 days); at the end of 4 cycles of induction therapy with the SA regimen (each cycle is 28 days).
Overall Survival
Time frame: Time from enrollment to all-cause death within 3 years
Event-free Survival
Time frame: Time from enrollment to treatment failure, relapse, or death from any cause within 3 years
Adverse Events
According to the CTCAE Version 6.0 criteria
Time frame: From the start of induction to 30 days after the completion of treatment
Time to neutrophil and platelet recovery
Time frame: From the start of induction to 30 days after the completion of treatment
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