Protocol Title: A Prospective, Randomized Controlled Study of Venetoclax Plus 3-Day Decitabine (DEC3-VEN) Versus Venetoclax Plus "2+6" DA Versus "3+7" DA Regimen in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)
Objective: This is a prospective, open-label, randomized, multicenter, phase II trial designed to compare the efficacy and safety of three induction regimens-Venetoclax plus 3-day Decitabine (DEC3-VEN), Venetoclax plus "2+6" DA, and standard "3+7" DA-in adult patients with newly diagnosed, intensifiable AML.
Study Design: The study employs a prospective, randomized, controlled, multicenter design. A total of 291 eligible patients will be enrolled across approximately 10 centers in China and randomized in a 2:2:1 ratio to the three treatment arms.
Key Eligibility Criteria:
Inclusion: Aged 16-65 with newly diagnosed non-APL AML (excluding favorable CBF-AML), eligible for intensive chemotherapy, ECOG ≤2, and adequate organ function.
Exclusion: Prior AML treatment, secondary AML, active severe infection, significant cardiac comorbidity, or known hypersensitivity to the study drugs.
Interventions:
Induction:
Arm A (VEN+"2+6"DA): Venetoclax (D1-8), Daunorubicin (D2-3), Cytarabine (D2-7).
Arm B (DEC3-VEN): Venetoclax (D1-14), Decitabine (D4-6). FLT3/ITD+ patients add Sorafenib or Gilteritinib (D8-14).
Arm C ("3+7"DA): Daunorubicin (D1-3), Cytarabine (D1-7).
Consolidation (2 cycles):
Arms A/B: Venetoclax + Intermediate-Dose Cytarabine.
Arm C: High-Dose Cytarabine.
Consolidation (Subsequent cycles):
All arms receive multiple cycles of DA or HA regimens.
Maintenance (6-8 cycles):
Arms A/B: Venetoclax + Azacitidine.
Arm C: Azacitidine.
Main Outcome Measures:
Primary Endpoint: Composite Complete Remission Rate (CR + CRi) after induction.
Secondary Endpoints: Overall Survival (OS), CR rate, MRD-negative rate, Relapse-Free Survival (RFS), Event-Free Survival (EFS), and safety.
Keywords: Acute Myeloid Leukemia, Venetoclax, Decitabine, Consolidation Therapy, Maintenance Therapy, Randomized Controlled Trial.
Except for APL or carrying t(8) that meet the diagnostic criteria (WHO2022 criteria) of the World Health Organization; 21)/(RUNX1::RUNX1TI)、inv(16)(p13.1q22) 、 t(16; 16) (p13.1q22) 、 t(16; 16)/CBFβ::myh11) and other acute myeloid leukemia other than one of the abnormal karyotypes;
Except for acute panmyeloproliferative disease with myelofibrosis and myeloid sarcoma, the World Health Organization AML classification is AML without separate classification;
Newly diagnosed AML patients with male or female, age greater than or equal to 16 years old and less than 65 years old, patients are considered suitable for intensive chemotherapy;
Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at the time of enrollment;
AML with BCR-ABL1; or CML sudden change period;
Treated patients (refers to those who have received induction chemotherapy in the past, regardless of the efficacy);
Subjects with acute panmyelopathy with myelofibrosis or myelosarcoma as defined by WHO 2016;
Secondary leukemia (mainly refers to those who belong to the treatment-related AML subcategory of the World Health Organization (WHO 2016) AML classification and those with a history of pre-stage MDS and/or MPD);
Parallel
Arm A (VEN+"2+6"DA)
Procedure/SurgeryVenetoclax (Days 1-8), Daunorubicin (Days 2-3), Cytarabine (Days 2-7)
Arm B (DEC3-VEN)
Procedure/SurgeryVenetoclax (Days 1-14), Decitabine (Days 4-6). FLT3/ITD-positive patients receive additional Sorafenib or Gilteritinib (Days 8-14).
Arm C ("3+7"DA)
Procedure/SurgeryDaunorubicin (Days 1-3), Cytarabine (Days 1-7)
Composite Complete Remission Rate after Induction Therapy
Percentage of patients achieving composite complete remission (CR + CRi) after induction therapy (defined as the first 28-day cycle of treatment). Complete remission (CR) and CR with incomplete hematologic recovery (CRi) are defined according to the European LeukemiaNet (ELN) 2022 criteria. Response is assessed by bone marrow aspiration and biopsy performed at a central laboratory between Day 21 and Day 28 of the induction cycle (or upon count recovery). The measurement unit is the percentage of patients achieving CR or CRi among all randomized patients (intention-to-treat population).
Overall Survival (OS)
Time from randomization to death from any cause (Overall Survival)， assessed using the Kaplan-Meier method， with the difference between treatment groups evaluated by the stratified log-rank test. The measurement unit is months.
MRD-negative remission rate
Percentage of patients achieving measurable residual disease (MRD) negativity， assessed by multiparameter flow cytometry (MFC) with a sensitivity threshold of 0.1% (10-³) in patients who achieved CR/CRi.
Relapse-Free Survival (RFS)
Time from first documented CR/CRi to confirmed hematologic relapse or death. Relapse defined per ELN 2022 criteria. Assessed by Kaplan-Meier method. Reported as median months with 95% CI.
Event-Free Survival (EFS)
Event-free survival， defined as the time from randomization to treatment failure (failure to achieve CR/CRi within 6 cycles)， confirmed relapse， or death from any cause， whichever occurs first， assessed using the Kaplan-Meier method. The measurement unit is months.
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The Second Affiliated Hospital of Kunming Medical University
Lead sponsor
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chines
Collaborator
Department of Hematology, Oncology Center, Tianjin Union Medical Center of Nankai University
Collaborator
Department of Hematology, Handan Central Hospital
Collaborator
Department of Hematology, The Affiliated Tai'an City Central Hospital of Qingdao University
Collaborator
Department of Hematology, The First Affiliated Hospital of Guangxi Medical University
Collaborator
Department of Hematology, The Second Xiangya Hospital, Central South University
Collaborator
Department of Hematology, Guizhou Provincial People's Hospital
Collaborator
People's Hospital of Guangxi Zhuang Autonomous Region
Collaborator
Affiliated Hospital of Qinghai University
Collaborator
