VA vs DA for Newly Diagnosed Hig-risk AML

NCT ID: NCT05939180

Last Updated: 2024-04-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2027-10-01

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VA regimen

VA regimen: azacytidine and venetoclax

Group Type: EXPERIMENTAL

Venetoclax Oral Tablet

Intervention Type: DRUG

VA regimen: azacytidine, 75mg/m2, subcutaneously, on days 1-7; venetoclax, orally, once a day, 100mg, d1; 200mg, d2; 400mg, days 3-28.

DA regimen

DA regimen: daunorubicin and cytarabine

Group Type: ACTIVE_COMPARATOR

Daunorubicin

Intervention Type: DRUG

DA regimen: daunorubicin (60mg/m2) on days 1-3, intraveneously injection, and cytarabine (100mg/m2) on days 1-7, intraveneously injection, for 1 cycle.

Interventions

Venetoclax Oral Tablet

VA regimen: azacytidine, 75mg/m2, subcutaneously, on days 1-7; venetoclax, orally, once a day, 100mg, d1; 200mg, d2; 400mg, days 3-28.

Intervention Type: DRUG

Daunorubicin

DA regimen: daunorubicin (60mg/m2) on days 1-3, intraveneously injection, and cytarabine (100mg/m2) on days 1-7, intraveneously injection, for 1 cycle.

Intervention Type: DRUG

Other Intervention Names

venetoclax plus azacytidine; daunorubicin plus cytarabine

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Su-ning Chen

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Soochow University

Locations

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Suzhou, Jiangsu, China

Site Status: RECRUITING

Ethical Committee of the First Affliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Su-ning Chen

Role: CONTACT

chensuning@sina.com

008613814881746

Facility Contacts

Suning Chen

Role: primary

chensuning@sina.com

13814881746

Zhou-lin Lu

Role: primary

13914086271

Other Identifiers

Victor AML-1

Identifier Type: -

Identifier Source: org_study_id