VA vs DA for Newly Diagnosed Hig-risk AML

Phase 2

Recruiting

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Venetoclax Oral Tablet; Drug: Daunorubicin

• Registration Number: NCT05939180
• Lead Sponsor: The First Affiliated Hospital of Soochow University

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 Timeline

• Status Verified: 2023-06
• Study First Submitted: 2023-07-03
• Study First Submitted QC: 2023-07-03
• Study First Posted: 2023-07-11
• Study Start: 2024-04-01
• Last Update Submitted: 2024-04-07
• Last Update Posted: 2024-04-09
• Primary Completion: 2025-10-01
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 116

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VA regimen	Venetoclax Oral Tablet	VA regimen: azacytidine and venetoclax
DA regimen	Daunorubicin	DA regimen: daunorubicin and cytarabine

Primary Outcome Measures

Name	Time	Method
Composite complete remission (CRc) after one course of induction therapy	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 Outcome Measures

Name	Time	Method
OS: overall survival	2 years	time from the date of enrollment to death from any cause or the last follow-up
AE	Within 60 days after randomization	Adverse events during the induction treatment.
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)	complete remission or complete remission with incomplete marrow recovery
Volume of infused blood products	Within 60 days after randomization	The volume of infused blood products during the induction treatment.
DOR: duration of remission	2 years	Time between the first remission and relapse
EFS：event-free survival	2 years	time from the date of enrollment to treatment failure, relapse, death from any cause or the last follow-up

Trial Locations

Locations (2)

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology; 🇨🇳 Suzhou, Jiangsu, China

Ethical Committee of the First Affliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China