Back to resultsVAH Versus VA for Salvage Therapy of R/R-AML
Primary Purpose
Venetoclax Combined With Azacitidine Plus Homoharringtonine, Venetoclax Combined With Azacitidine
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
VEN combined with azacitidine plus homoharringtonine
VEN combined with azacitidine
Sponsored by
About this trial
This is an interventional treatment trial for Venetoclax Combined With Azacitidine Plus Homoharringtonine focused on measuring Relapsed/refractory acute myeloid leukemia
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Department of Hematology,Nanfang Hospital, Southern Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
VAH regimen
VA regimen
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Overall response rate
Overall response including CR/CRi and PR
Secondary Outcome Measures
Composite complete remission rate
Composite complete remission including CR/CRi
Overall survival
The time from enrolling to death or the last follow up
Event-free survival
The time from enrolling to no response, relapse, death or the last follow up
Relapse
The event of relapse
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Haematological toxicity and non-haematological toxicity
Full Information
NCT ID
NCT05457361
First Posted
March 8, 2022
Last Updated
July 9, 2022
Sponsor
Nanfang Hospital, Southern Medical University
Collaborators
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Zhongshan People's Hospital, Guangdong, China, Shenzhen Hospital of Southern Medical University, Peking University Shenzhen Hospital, Shenzhen Second People's Hospital, The Seventh Affiliated Hospital of Sun Yat-sen University, Southern Medical University, China, First People's Hospital of Chenzhou, The Affiliated Hospital of Qingdao University, First Affiliated Hospital of Guangxi Medical University
1. Study Identification
Unique Protocol Identification Number
NCT05457361
Brief Title
VAH Versus VA for Salvage Therapy of R/R-AML
Official Title
Venetoclax Combined With Azacitidine Plus Homoharringtonine Versus Venetoclax Combined With Azacitidine for Relapsed/Refractory Acute Myeloid Leukemia：an Open-label, Multicentre, Randomised Phase 3 Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2022 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Nanfang Hospital, Southern Medical University
Collaborators
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Zhongshan People's Hospital, Guangdong, China, Shenzhen Hospital of Southern Medical University, Peking University Shenzhen Hospital, Shenzhen Second People's Hospital, The Seventh Affiliated Hospital of Sun Yat-sen University, Southern Medical University, China, First People's Hospital of Chenzhou, The Affiliated Hospital of Qingdao University, First Affiliated Hospital of Guangxi Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venetoclax Combined With Azacitidine Plus Homoharringtonine, Venetoclax Combined With Azacitidine
Keywords
Relapsed/refractory acute myeloid leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
162 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
VAH regimen
Arm Type
Experimental
Arm Description
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.
Arm Title
VA regimen
Arm Type
Active Comparator
Arm Description
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
Intervention Name(s)
VEN combined with azacitidine plus homoharringtonine
Intervention Description
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
Intervention Name(s)
VEN combined with azacitidine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall response rate
Description
Overall response including CR/CRi and PR
Time Frame
At the end of Cycle 2 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Composite complete remission rate
Description
Composite complete remission including CR/CRi
Time Frame
At the end of Cycle 2 (each cycle is 28 days)
Title
Overall survival
Description
The time from enrolling to death or the last follow up
Time Frame
From date of randomization until date of death from any cause, assessed up to 12 months.
Title
Event-free survival
Description
The time from enrolling to no response, relapse, death or the last follow up
Time Frame
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
Title
Relapse
Description
The event of relapse
Time Frame
1 year
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Haematological toxicity and non-haematological toxicity
Time Frame
Baseline to 30 day post the salvage therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qifa Liu
Phone
86-20-61641612
Email
liuqifa628@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qifa Liu
Organizational Affiliation
Department of Hematology,Nanfang Hospital, Southern Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Hematology,Nanfang Hospital, Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qifa Liu
Phone
86-20-61641612
Email
liuqifa628@163.com
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
VAH Versus VA for Salvage Therapy of R/R-AML
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