VA vs DA for Newly Diagnosed Hig-risk AML

Soochow University

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Daunorubicin; Drug: Venetoclax Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT05939180

Victor AML-1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 116 estimated patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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116 participants in 2 patient groups

VA regimen

Experimental group

Description:

VA regimen: azacytidine and venetoclax

Treatment:

Drug: Venetoclax Oral Tablet

DA regimen

Active Comparator group

Description:

DA regimen: daunorubicin and cytarabine

Treatment:

Drug: Daunorubicin