VAH Versus VA for Salvage Therapy of R/R-AML

NCT ID: NCT05457361

Last Updated: 2022-07-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 162 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2023-12-31

Brief Summary

This is a prospective, multi-center, phase 3 randomized controlled clinical study comparing VAH and VA regimens for the salvage treatment of the patients with relapsed/refractory AML. Approximately 164 subjects will be randomized in a 1:1 ratio to receive VAH regimen (82 subjects) or VA regimen (82 subjects) for salvage therapy. Randomization is done with permuted blocks (block size four), and implemented through an interactive web-based response system.

VAH regimen: VEN begins at 100 mg on day 1 and increases stepwise over 3 days to reach the target dose of 400 mg (100 mg, 200 mg, 400 mg); dosing is continued at 400 mg per day from day 4 through day 14; azacitidine (75 mg/m²) is administered subcutaneously on days 1-7, and HHT (1 mg/m²) on days 1-7.

VA regimen: The use of VEN is just the same as it dose in VAH regimen except lasting for 28 days. The use of azacitidine is exactly the same as VAH group does.

The primary endpoint was overall response rate (ORR) after 2 cycles of trial therapy.

The secondary endpoints were CRc after 2 cycles of trial therapy, overall survival (OS), event-free survival (EFS) and relapse at 2 year, and safety.

Conditions

Venetoclax Combined With Azacitidine Plus Homoharringtonine; Venetoclax Combined With Azacitidine

Study Design

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

Study Groups

VAH regimen

VEN begins at 100 mg on day 1 and increases stepwise over 3 days to reach the target dose of 400 mg (100 mg, 200 mg, 400 mg); dosing is continued at 400 mg per day from day 4 through day 14; azacitidine (75 mg/m²) is administered subcutaneously on days 1-7, and HHT (1 mg/m²) on days 1-7.

Group Type: EXPERIMENTAL

VEN combined with azacitidine plus homoharringtonine

Intervention Type: DRUG

VEN begins at 100 mg on day 1 and increases stepwise over 3 days to reach the target dose of 400 mg (100 mg, 200 mg, 400 mg); dosing is continued at 400 mg per day from day 4 through day 14; azacitidine (75 mg/m²) is administered subcutaneously on days 1-7, and HHT (1 mg/m²) on days 1-7.

VA regimen

The use of VEN is just the same as it dose in VAH regimen except lasting for 28 days. The use of azacitidine is exactly the same as VAH group does.

Group Type: ACTIVE_COMPARATOR

VEN combined with azacitidine

Intervention Type: DRUG

The use of VEN is just the same as it dose in VAH regimen except lasting for 28 days. The use of azacitidine is exactly the same as VAH group does.

Interventions

VEN combined with azacitidine plus homoharringtonine

VEN begins at 100 mg on day 1 and increases stepwise over 3 days to reach the target dose of 400 mg (100 mg, 200 mg, 400 mg); dosing is continued at 400 mg per day from day 4 through day 14; azacitidine (75 mg/m²) is administered subcutaneously on days 1-7, and HHT (1 mg/m²) on days 1-7.

Intervention Type: DRUG

VEN combined with azacitidine

The use of VEN is just the same as it dose in VAH regimen except lasting for 28 days. The use of azacitidine is exactly the same as VAH group does.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with relapsed/refractory AML The diagnosis of AML or relapsed AML was based on the criteria from NCCN, defined as recurrence of blasts in the peripheral blood (PB) or bone marrow (BM) blasts > 5% or development of extramedullary disease of patients after achieving a CR. Refractory AML was defined as no composite complete remission (CRc) and a reduction in bone marrow blasts of less than 50% after one cycle or no CRc after two cycles.

2. Age 18 to 65 years old with Eastern Cooperative Oncology Group (ECOG) performance status 0-2

3. Sign informed consent form, have the ability to comply with study and follow-up procedures

Exclusion Criteria

1. Acute promyelocytic leukemia (AML subtype M3)

2. Previous exposure to the treatment of VEN-based regimen

3. Life expectancy less than 30 days after salvage therapy

4. Cardiac dysfunction (particularly congestive heart failure, unstable coronary artery disease and serious cardiac ventricular arrhythmias requiring antiarrhythmic therapy)

5. Respiratory failure ( PaO2 ≤60mmHg)

6. Hepatic abnormalities (total bilirubin ≥2 times the upper limit of normal [ULN], alanine aminotransferase or aspartate aminotransferase ≥2 times the ULN)

7. Renal dysfunction (creatinine ≥2 times the ULN or creatinine clearance rate < 30 mL/min)

8. ECOG performance status 3, 4 or 5

9. With any conditions not suitable for the trial (investigators' decision)

10. Active acute or chronic graft-versus-host disease (GVHD). Active acute GVHD or chronic GVHD was defined as GVHD requiring either at least 1 mg/kg per day of prednisone (or equivalent) or treatment beyond systemic corticosteroids.

11. Patients with pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Zhongshan People's Hospital, Guangdong, China

OTHER

Sponsor Role: collaborator

Shenzhen Hospital of Southern Medical University

OTHER

Sponsor Role: collaborator

Peking University Shenzhen Hospital

OTHER

Sponsor Role: collaborator

Shenzhen Second People's Hospital

OTHER

Sponsor Role: collaborator

The Seventh Affiliated Hospital of Sun Yat-sen University

OTHER

Sponsor Role: collaborator

Southern Medical University, China

OTHER

Sponsor Role: collaborator

First People's Hospital of Chenzhou

OTHER

Sponsor Role: collaborator

The Affiliated Hospital of Qingdao University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Guangxi Medical University

OTHER

Sponsor Role: collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: lead

Responsible Party

Qifa Liu

Department director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qifa Liu

Role: PRINCIPAL_INVESTIGATOR

Department of Hematology,Nanfang Hospital, Southern Medical University

Locations

Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Qifa Liu

Role: CONTACT

liuqifa628@163.com

86-20-61641612

Facility Contacts

Qifa Liu

Role: primary

liuqifa628@163.com

86-20-61641612

Other Identifiers

VAH vs VA-2022

Identifier Type: -

Identifier Source: org_study_id