Back to resultsVenetoclax Combined With Azacitidine and CAG in Refractory/Relapse Acute Myeloid Leukemia
Primary Purpose
Refractory/Relapse Acute Myeloid Leukemia
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Refractory/Relapse Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria: Patients ≥ 18 years old and ≤ 65 years old Refractory/Relapse AML patients according to 2016 World Health Organization (WHO) classification; Eastern Cooperative Oncology Group (ECOG) Performance status score less than 3; Liver function: Total bilirubin ≦2 upper limit of normal (ULN); aspartate aminotransferase (AST) ≦3 ULN; alanine aminotransferase (ALT)≦3 ULN Renal function：Ccr（Creatinine Clearance Rate） ≧30 ml/min; Scr (serum creatinine) ≦2 ULN Heart function: left ventricular ejection fraction ≧45% Patients must participate in this clinical trial voluntarily and sign an informed consent form. Exclusion Criteria: Other diseases； AML with central nervous system (CNS) infiltration； Patients have received prior CAG or VA regimen before； Patients with a life expectancy <3 months Patients with uncontrolled active infection; HIV infection; Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. b) An active second cancer that requires treatment within 6 months of study entry Female who are pregnant, breast feeding or childbearing potential. Patients deemed unsuitable for enrollment by the investigator;
Sites / Locations
- Department of Hematology,920th Hospital of Joint Logistic Support Force of People's LiberationRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
VACAG（Venetoclax Combined with Azacitidine and CAG）regimen
Arm Description
Participants will receive induction as azacitidine on days 1-7, venetoclax aily on days 1-28, cytarabine q12h on days 1-7, aclacinomycin on days 1,3,5,7, and granulocyte colony-stimulating factor on days 0-8. Participants will receive second induction if not reach complete remission.
Outcomes
Primary Outcome Measures
Overall response rate (ORR)
The overall remission rate (ORR) was defined as the percentage of patients who achieved complete remission (CR), complete remission with incomplete count recovery (CRi), or morphologic leukemia free state (MLFS) per the International Working Group criteria for AML.
Secondary Outcome Measures
Rate of Minimal Residual Disease (MRD) negativity
Percentage of participants who converted to MRD < 10^-3 by flow cytometry before initiation of consolidation therapy.
Incidence of Treatment-Emergent Adverse Events
Safety and tolerability analysis will be assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Duration of myelosuppression
The duration of absolute value of peripheral blood neutrophils <0.5×10^9/L and platelet count <50×10^9/L during myelosuppression.
Leukaemia-free survival
Leukaemia-free survival will be defined as the time since date of CR until either relapse or death in remission.
Overall survival
Overall Survival be defined as the time from administration of the initial doses until death from any cause.
Full Information
NCT ID
NCT05807347
First Posted
February 27, 2023
Last Updated
March 28, 2023
Sponsor
Hematology department of the 920th hospital
1. Study Identification
Unique Protocol Identification Number
NCT05807347
Brief Title
Venetoclax Combined With Azacitidine and CAG in Refractory/Relapse Acute Myeloid Leukemia
Official Title
Phase II Trial of Venetoclax in Combination With Azacitidine and CAG as Induction Therapy in Patients With Refractory/Relapse Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2023 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
February 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hematology department of the 920th hospital
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 study aims to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine and CAG as induction regimen in Patients with Refreactory/Relapse Acute Myeloid Leukemia.
Detailed Description
This is an open-label, multicenter, phase II clinical trial to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine (VA) and CAG (G-CSF priming, low dose cytarabine, and aclarubicin) as induction regimen in Patients with Refreactory/Relapse Acute Myeloid Leukemia(AML).
Previous studies have shown that venetoclax plus intense chemotherapy represent promising efficacy in de novo AML patients with high complete remission rates and good tolerance. Our preliminary results suggest that venetoclax in combination with azacitidine and CAG are well tolerated and effective for patients who were diagnosed with refreactory/relapse AML. Thus, this phase II clinical trial is going to further explore its efficacy and safety. It is expected that about 42 patients will take part in this trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory/Relapse Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
Open lable
Allocation
N/A
Enrollment
42 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
VACAG（Venetoclax Combined with Azacitidine and CAG）regimen
Arm Type
Experimental
Arm Description
Participants will receive induction as azacitidine on days 1-7, venetoclax aily on days 1-28, cytarabine q12h on days 1-7, aclacinomycin on days 1,3,5,7, and granulocyte colony-stimulating factor on days 0-8. Participants will receive second induction if not reach complete remission.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
Azacitidine, Cytarabine, Aclacinomycin, Granulocyte colony-stimulating factor
Intervention Description
VA regimen Drug: Venetoclax orally once daily (100 mg d1, 200 mg d2, 400 mg d3-21); Drug: Azacitidine 75 mg/m2 subcutaneously once daily on days 1-7. CAG regimen Drug: Cytarabine 10mg/m2 subcutaneously q12h on days 1-7 Drug: Aclacinomycin 12-14mg/m2 on days 1,3,5,7 Drug: Granulocyte colony-stimulating factor 5ug/kg on days 0-8, discontinue if WBC >20×109/L
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
The overall remission rate (ORR) was defined as the percentage of patients who achieved complete remission (CR), complete remission with incomplete count recovery (CRi), or morphologic leukemia free state (MLFS) per the International Working Group criteria for AML.
Time Frame
up to 2 cycles from the start of VACAG regimen (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Rate of Minimal Residual Disease (MRD) negativity
Description
Percentage of participants who converted to MRD < 10^-3 by flow cytometry before initiation of consolidation therapy.
Time Frame
up to 2 years
Title
Incidence of Treatment-Emergent Adverse Events
Description
Safety and tolerability analysis will be assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Time Frame
up to 2 years
Title
Duration of myelosuppression
Description
The duration of absolute value of peripheral blood neutrophils <0.5×10^9/L and platelet count <50×10^9/L during myelosuppression.
Time Frame
up to 2 years
Title
Leukaemia-free survival
Description
Leukaemia-free survival will be defined as the time since date of CR until either relapse or death in remission.
Time Frame
up to 2 years
Title
Overall survival
Description
Overall Survival be defined as the time from administration of the initial doses until death from any cause.
Time Frame
up to 2 years
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 ≥ 18 years old and ≤ 65 years old
Refractory/Relapse AML patients according to 2016 World Health Organization (WHO) classification;
Eastern Cooperative Oncology Group (ECOG) Performance status score less than 3;
Liver function: Total bilirubin ≦2 upper limit of normal (ULN); aspartate aminotransferase (AST) ≦3 ULN; alanine aminotransferase (ALT)≦3 ULN
Renal function：Ccr（Creatinine Clearance Rate） ≧30 ml/min; Scr (serum creatinine) ≦2 ULN
Heart function: left ventricular ejection fraction ≧45%
Patients must participate in this clinical trial voluntarily and sign an informed consent form.
Exclusion Criteria:
Other diseases；
AML with central nervous system (CNS) infiltration；
Patients have received prior CAG or VA regimen before；
Patients with a life expectancy <3 months
Patients with uncontrolled active infection;
HIV infection;
Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. b) An active second cancer that requires treatment within 6 months of study entry
Female who are pregnant, breast feeding or childbearing potential.
Patients deemed unsuitable for enrollment by the investigator;
Facility Information:
Facility Name
Department of Hematology,920th Hospital of Joint Logistic Support Force of People's Liberation
City
Kunming
State/Province
Yunnan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lin Liu, Professor
Phone
0871-64774206
Email
Wangsanbin2022@126.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Venetoclax Combined With Azacitidine and CAG in Refractory/Relapse Acute Myeloid Leukemia
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