Back to resultsA Clinical Study of VA-CAG as Induction Therapy in Newly Diagnosed AML Patients
Primary Purpose
Acute Myeloid Leukemia
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Venetoclax in combination with azacitidine and CAG
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Venetoclax, Azacitidine, Granulocyte colony-stimulating factor(G-CSF), Cytarabine, Aclarubicin
Eligibility Criteria
Inclusion Criteria: Patients ≥ 18 years old and ≤ 65 years old Newly diagnosed as AML patients according to 2016 World Health Organization (WHO) classification; Patients without receiving prior therapy for AML; 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: Acute promyeloid leukemia； AML with central nervous system (CNS) infiltration； Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML； 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
- 920th Hospital of Joint Logistics Support Force of People's Liberation Army of ChinaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment group
Arm Description
Induction: Subjects who meet the enrollment conditions will receive Venetoclax plus Azacitidine and CAG(VA-CAG) . Participants will receive this induction Therapy 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. Consolidation: If patients are intermediate or poor risk and have plans for allogeneic hematopoietic stem-cell transplantation(allo-HSCT) , high dose cytarabine (3g/m2 q12h days 1-3) for 1-2 cycles and follow up with allo-HSCT. In other cases, high dose cytarabine for 4 cycles.
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
Incidence of Treatment-Emergent Adverse Events (>=grade 3 )
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 will be defined as the time from administration of the initial doses until death from any cause.
Rate of Minimal Residual Disease (MRD) negativity
Percentage of participants who converted to MRD < 10^-3 by flow cytometry before initiation of consolidation therapy.
Full Information
NCT ID
NCT05662956
First Posted
December 10, 2022
Last Updated
December 20, 2022
Sponsor
Hematology department of the 920th hospital
1. Study Identification
Unique Protocol Identification Number
NCT05662956
Brief Title
A Clinical Study of VA-CAG as Induction Therapy in Newly Diagnosed AML Patients
Official Title
A Phase II Study to Evaluate the Safety and Efficacy of Venetoclax in Combination With Azacitidine and CAG(VA-CAG) as Induction Therapy in Newly Diagnosed Patients With Acute Myeloid Leukemia(AML)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (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
5. Study Description
Brief Summary
This study aims to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine and CAG(VA-CAG) as induction regimen in newly diagnosed young patients with acute myeloid leukemia(AML).
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 newly diagnosed patients with acute myeloid leukemia (AML).
The combination of venetoclax and azacitidine is the standard therapy for elderly (> 60 year old) patients with newly diagnosed AML who are not eligible for intensive chemotherapy. 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. The preliminary results suggest that venetoclax in combination with azacitidine and CAG are well tolerated and effective for newly diagnosed young patients with AML. Thus, this phase II clinical trial is going to further explore its efficacy and safety. It is expected that about 62 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
Acute Myeloid Leukemia
Keywords
Venetoclax, Azacitidine, Granulocyte colony-stimulating factor(G-CSF), Cytarabine, Aclarubicin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
62 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment group
Arm Type
Experimental
Arm Description
Induction: Subjects who meet the enrollment conditions will receive Venetoclax plus Azacitidine and CAG(VA-CAG) . Participants will receive this induction Therapy 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.
Consolidation: If patients are intermediate or poor risk and have plans for allogeneic hematopoietic stem-cell transplantation(allo-HSCT) , high dose cytarabine (3g/m2 q12h days 1-3) for 1-2 cycles and follow up with allo-HSCT. In other cases, high dose cytarabine for 4 cycles.
Intervention Type
Drug
Intervention Name(s)
Venetoclax in combination with azacitidine and CAG
Other Intervention Name(s)
VA-CAG regimen
Intervention Description
Induction:
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 >20×10^9/L；
Consolidation:
Drug: Cytarabine 3g/m2 q12h on days 1-3.
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
At the end of Cycle 1 and Cycle 2 of induction(each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events (>=grade 3 )
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 will be defined as the time from administration of the initial doses until death from any cause.
Time Frame
Up to 2 years
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
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
Newly diagnosed as AML patients according to 2016 World Health Organization (WHO) classification;
Patients without receiving prior therapy for AML;
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:
Acute promyeloid leukemia；
AML with central nervous system (CNS) infiltration；
Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML；
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sanbin Wang, MD
Phone
13187424131
Ext
+86
Email
Wangsanbin2022@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Lin Liu, MD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sanbin Wang, MD
Organizational Affiliation
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Official's Role
Principal Investigator
Facility Information:
Facility Name
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lin Liu
12. IPD Sharing Statement
Learn more about this trial
A Clinical Study of VA-CAG as Induction Therapy in Newly Diagnosed AML Patients
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