VA vs DA for Newly Diagnosed Hig-risk AML

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax Oral Tablet; Drug: Daunorubicin

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 Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Su-ning Chen; Phone Number: 008613814881746; Email: chensuning@sina.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
      • Contact: Suning Chen; Phone Number: 13814881746; Email: chensuning@sina.com
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • Ethical Committee of the First Affliated Hospital of Soochow University
      • Contact: Zhou-lin Lu; Phone Number: 13914086271

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VA regimen; VA regimen: azacytidine and venetoclax	Drug: 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.; Other Names: venetoclax plus azacytidine
Active Comparator: DA regimen; DA regimen: daunorubicin and cytarabine	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.; Other Names: daunorubicin plus cytarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite complete remission (CRc) after one course of induction therapy	Rates of complete remission plus complete remission with incomplete blood cell rates of complete remission or complete remission with incomplete marrow recovery	From randomization to the end of the first course of induction therapy (within 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DOR: duration of remission	Time between the first remission and relapse	2 years
EFS：event-free survival	time from the date of enrollment to treatment failure, relapse, death from any cause or the last follow-up	2 years
OS: overall survival	time from the date of enrollment to death from any cause or the last follow-up	2 years
Volume of infused blood products	The volume of infused blood products during the induction treatment.	Within 60 days after randomization
AE	Adverse events during the induction treatment.	Within 60 days after randomization
Composite complete remission (CRc) after two courses of induction therapy	complete remission or complete remission with incomplete marrow recovery	From randomization to the end one and two courses of induction therapy (within 60 days)

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Su-ning Chen, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: July 3, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Adverse risk, newly diagnosed, induction therapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Venetoclax; Azacitidine; Cytarabine; Daunorubicin
• Other Study ID Numbers: Victor AML-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No