Clinical trial NCT05939180: VA vs DA for Newly Diagnosed Hig-risk AML
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: Adverse risk, newly diagnosed, induction therapy
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2023-07-11
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Gender: female or male.
2. Age:18-64 years old.
3. Patients with newly diagnosed AML according to the WHO 2022 classification.
4. AML patients with adverse risk features according to the 2022 European Leukemia Net risk stratification.
5. Untreated AML (hydroxyurea, and low dose cytarabine with cummulative dose \<1.0g are permitted).
6. ECOG: 0-2.
7. 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) .
8. Adequate Renal function: Ccr (Creatinine Clearance Rate) ≥30 ml/min.
9. Be able to understand and be willing to participate in the study. Be able to provide written informed consent.

Exclusion Criteria:

1. Patients with acute promyeloid leukemia.
2. AML with central nervous system infiltration.
3. Patients diagnosed with myeloid sarcoma.
4. Patients have AML secondary to MDS and previously been treated with hypomethylating agents.
5. Patients with active infection, which is considered as uncontrollable by the investigator.
6. Patients with active hepatitis B, hepatitis C and HIV infection.
7. Patients with heart failure (grade 3-4);
8. Patients who are pregnant or breastfeeding.
9. Patients who refused to be enrolled in the study. Patients who are considered as ineligible for the enrollment by the investigators.

Primary outcomes:
measure: Composite complete remission (CRc) after one course of induction therapy
timeFrame: From randomization to the end of the first course of induction therapy (within 28 days)
Secondary outcomes:
measure: DOR: duration of remission
timeFrame: 2 years
measure: EFS：event-free survival
timeFrame: 2 years
measure: OS: overall survival
timeFrame: 2 years
measure: Volume of infused blood products
timeFrame: Within 60 days after randomization
measure: AE
timeFrame: Within 60 days after randomization
measure: Composite complete remission (CRc) after two courses of induction therapy
timeFrame: From randomization to the end one and two courses of induction therapy (within 60 days)
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
state: Jiangsu
city: Suzhou
country: China
facility: Ethical Committee of the First Affliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Su-ning Chen
role: PRINCIPAL_INVESTIGATOR
References: