Study of the Efficacy and Safety of Venetoclax Plus Azacytidine Versus Daunorubicin Plus Cytarabine in Adult Acute Myeloid Leukemia (AML) Patients With Adverse Risk Features
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- The First Affiliated Hospital of Soochow University
- Enrollment
- 116
- Locations
- 2
- Primary Endpoint
- Composite complete remission (CRc) after one course of induction therapy
Overview
Brief Summary
This is an open-label, multicenter, phase 2b, randomized study aiming to compare the efficacy and safety of venetoclax plus azacytidine Versus daunorubicin plus cytarabine (conventional 7+3 regimen) in adult acute myeloid leukemia (AML) patients with adverse risk featuress. Participants will be 1:1 randomly assigned to the VA and DA groups. Once remission was achieved, consolidated chemotherapy will be performed and allogeneic hematopoietic stem cell transplantation is strongly recommended. After completion of the study intervention, participants will be followed-up every 1 to 2 months for up to 2 years.
Detailed Description
This is an open-label, multicenter, phase 2b, randomized study aiming to compare the efficacy and safety of venetoclax plus azacytidine Versus daunorubicin plus cytarabine (conventional 7+3 regimen) in adult acute myeloid leukemia (AML) patients with adverse risk featuress. Newly diagnosed AML patients with adverse risk features according to 2022 European Leukemia Net risk stratification will be enrolled. In the study, a novel second generation targeted sequencing panel for the fast screening of adverse mutations with 72-hours after the bone marrow samples will be utilized. Randomized participants will receive induction treatment . Participants will be 1:1 randomly assigned to the VA and DA groups. VA regimen comprises of azacytidine, 75mg/m2, subcutaneously, on days 1-7; venetoclax, orally, once a day, 100mg, d1; 200mg, d2; 400mg, days 3-28. DA regimen comprises of daunorubicin (60mg/m2) on days 1-3, intraveneously injection, and cytarabine (100mg/m2) on days 1-7, intraveneously injection, for 1 cycle. Once remission was achieved, consolidated chemotherapy will be performed and allogeneic hematopoietic stem cell transplantation is strongly recommended. After completion of the study intervention, participants will be followed-up every 1 to 2 months for up to 2 years.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 64 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Gender: female or male.
- •Age:18-64 years old.
- •Patients with newly diagnosed AML according to the WHO 2022 classification.
- •AML patients with adverse risk features according to the 2022 European Leukemia Net risk stratification.
- •Untreated AML (hydroxyurea, and low dose cytarabine with cummulative dose \<1.0g are permitted).
- •Adequate liver function: Total bilirubin ≤ 1.5×upper limit of normal (ULN); aspartate aminotransferase (AST) ≤3×ULN (liver infiltration of leukemia: ≤5×ULN); alanine aminotransferase (ALT)≤3×ULN (liver infiltration of leukemia: ≤5×ULN) .
- •Adequate Renal function: Ccr (Creatinine Clearance Rate) ≥30 ml/min.
- •Be able to understand and be willing to participate in the study. Be able to provide written informed consent.
Exclusion Criteria
- •Patients with acute promyeloid leukemia.
- •AML with central nervous system infiltration.
- •Patients diagnosed with myeloid sarcoma.
- •Patients have AML secondary to MDS and previously been treated with hypomethylating agents.
- •Patients with active infection, which is considered as uncontrollable by the investigator.
- •Patients with active hepatitis B, hepatitis C and HIV infection.
- •Patients with heart failure (grade 3-4);
- •Patients who are pregnant or breastfeeding.
- •Patients who refused to be enrolled in the study. Patients who are considered as ineligible for the enrollment by the investigators.
Arms & Interventions
VA regimen
VA regimen: azacytidine and venetoclax
Intervention: Venetoclax Oral Tablet (Drug)
DA regimen
DA regimen: daunorubicin and cytarabine
Intervention: Daunorubicin (Drug)
Outcomes
Primary Outcomes
Composite complete remission (CRc) after one course of induction therapy
Time Frame: From randomization to the end of the first course of induction therapy (within 28 days)
Rates of complete remission plus complete remission with incomplete blood cell rates of complete remission or complete remission with incomplete marrow recovery
Secondary Outcomes
- OS: overall survival(2 years)
- AE(Within 60 days after randomization)
- Composite complete remission (CRc) after two courses of induction therapy(From randomization to the end one and two courses of induction therapy (within 60 days))
- Volume of infused blood products(Within 60 days after randomization)
- DOR: duration of remission(2 years)
- EFS：event-free survival(2 years)