VA vs DA for Newly Diagnosed Hig-risk AML

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05939180
• Other study ID #: Victor AML-1
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: April 1, 2024
• Est. completion date: October 1, 2027

Study information

• Verified date: June 2023
• Source: The First Affiliated Hospital of Soochow University
• Contact: Su-ning Chen
• Phone: 008613814881746
• Email: chensuning[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 116
• Est. completion date: October 1, 2027
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Ethical Committee of the First Affliated Hospital of Soochow University	Suzhou	Jiangsu
China	The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	DOR: duration of remission	Time between the first remission and relapse	2 years
Secondary	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
Secondary	OS: overall survival	time from the date of enrollment to death from any cause or the last follow-up	2 years
Secondary	Volume of infused blood products	The volume of infused blood products during the induction treatment.	Within 60 days after randomization
Secondary	AE	Adverse events during the induction treatment.	Within 60 days after randomization
Secondary	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)