VA vs DA for ND Hig-risk AML

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05939180

Collaborator

(none)

108

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Venetoclax Oral Tablet Drug: Daunorubicin	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) [From randomization to the end of induction therapy (before consolidation therapy, within 60 days)]
Rates of complete remission/complete remission with incomplete count recovery/morphologic leukemia free state.

Secondary Outcome Measures

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
OS: overall survival [2 years]
time from the date of enrollment to death from any cause or the last follow-up
Volume of infused blood products [Within 60 days after randomization]
The volume of infused blood products during the induction treatment.
AE [Within 60 days after randomization]
Adverse events during the induction treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology	Suzhou	Jiangsu	China	215000
2	Ethical Committee of the First Affliated Hospital of Soochow University	Suzhou	Jiangsu	China	215006