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

NCT05457361 | Unknown Phase 3 DMC

• 1 other identifier: VAH vs VA-2022
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

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

Keywords

Relapsed/refractory acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Overall response including CR/CRi and PR

  At the end of Cycle 2 (each cycle is 28 days)

Secondary Outcomes (5)

• Composite complete remission rate

  At the end of Cycle 2 (each cycle is 28 days)

• Overall survival

  From date of randomization until date of death from any cause, assessed up to 12 months.

• Event-free survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

• Relapse

  1 year

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Baseline to 30 day post the salvage therapy

Study Arms (2)

VAH regimen

EXPERIMENTAL

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.

Drug: VEN combined with azacitidine plus homoharringtonine

VA regimen

ACTIVE COMPARATOR

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.

Drug: VEN combined with azacitidine

Interventions

VEN combined with azacitidine plus homoharringtonine 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.

VAH regimen

VEN combined with azacitidine 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.

VA regimen

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age 18 to 65 years old with Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Sign informed consent form, have the ability to comply with study and follow-up procedures

You may not qualify if:

• Acute promyelocytic leukemia (AML subtype M3)
• Previous exposure to the treatment of VEN-based regimen
• Life expectancy less than 30 days after salvage therapy
• Cardiac dysfunction (particularly congestive heart failure, unstable coronary artery disease and serious cardiac ventricular arrhythmias requiring antiarrhythmic therapy)
• Respiratory failure ( PaO2 ≤60mmHg)
• Hepatic abnormalities (total bilirubin ≥2 times the upper limit of normal \[ULN\], alanine aminotransferase or aspartate aminotransferase ≥2 times the ULN)
• Renal dysfunction (creatinine ≥2 times the ULN or creatinine clearance rate \< 30 mL/min)
• ECOG performance status 3, 4 or 5
• With any conditions not suitable for the trial (investigators' decision)
• 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.
• Patients with pregnancy

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator
• Zhongshan People's Hospital, Guangdong, China: collaborator
• Shenzhen Hospital of Southern Medical University: collaborator
• Peking University Shenzhen Hospital: collaborator
• Shenzhen Second People's Hospital: collaborator
• The Seventh Affiliated Hospital of Sun Yat-sen University: collaborator
• Southern Medical University, China: collaborator
• First People's Hospital of Chenzhou: collaborator
• The Affiliated Hospital of Qingdao University: collaborator
• First Affiliated Hospital of Guangxi Medical University: collaborator

Study Sites (1)

Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; Homoharringtonine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Harringtonines; Alkaloids; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Study Officials

• Qifa Liu

  Department of Hematology,Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qifa Liu

CONTACT

86-20-61641612; liuqifa628@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department director

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: July 14, 2022
• Study Start: March 1, 2022
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: July 14, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)