Back to resultsClinical Study of Venetoclax Combined With CACAG Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
Primary Purpose
Relapsed/Refractory Acute Myeloid Leukemia
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor
Best-Available Therapy(BAT) Regimen
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed/Refractory Acute Myeloid Leukemia focused on measuring Relapsed/Refractory Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria: Patients who are able to understand and willing to sign the informed consent form (ICF). All patients should aged 14 to 75 years,no gender limitation. Patients with R/R AML, diagnosed in accordance with the 2021 edition of the CMA criteria Liver function: ALT and AST≤2.5 times the upper limit of normal ,bilirubin≤2 times the upper limit of normal; Renal function: creatinine ≤the upper limit of normal; Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness; The score of Eastern Cooperative Oncology Group (ECOG) is 0-3,and the predicted survival ≥ 4 months. Patients without severe allergic constitution. Exclusion Criteria: Patients with allergy or contraindication to the study drug; Female patients who are pregnant or breast-feeding. Patients with a known history of alcohol or drug addiction on the basis that there could be a higher risk of non-compliance to study treatment; Patients with mental illness or other states unable to comply with the protocol; Less than 6 weeks after surgical operation of important organs. Liver function: ALT and AST>2.5 times the upper limit of normal ,bilirubin>2 times the upper limit of normal;Renal function: creatinine >the upper limit of normal; The patient is not suitable for this clinical trial (poor compliance, substance abuse, etc.)
Sites / Locations
- Chinese PLA General HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Venetoclax Combined With CACAG Regimen
Best-Available Therapy(BAT) Regimen
Arm Description
Venetoclax combined with CACAG regimen for relapsed/refractory AML. Recipients were randomized and those entering the experimental group received azacytidine,cytarabine,aclacinomycin,chidamide,venetoclax and granulocyte colony-stimulating factor. Azacytidine was used as 75 mg/m2/day from day 1 to day 7.Cytarabine was used as 75-100 mg/m2 bid from day 1 to day 5. Aclacinomycin was used as 20 mg/day on days 1,3,5. Chidamide was used as 30 mg/day on days 1,4,8,11. Venetoclax was used as 400 mg/day from day 1 to day 14.Granulocyte colony-stimulating factor was used as 300 ug/day from day 0 until agranulocytosi recovery.
BAT regimen for relapsed/refractory AML.Recipients were randomized and those entering this group received FLAG/CLAG/MAE/DCAG/HAA/HAD regimen.
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR) after 1 course of treatment
Defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi), or partial response (PR).Biological characteristics exploratory studies were analyzed by single-cell sequencing and Atac-seq. Further, according to European LeukemiaNet risk group, we analyzed the outcomes of patients by molecular subtype as a sub-group analysis.
Secondary Outcome Measures
Complete Remission (CR) Rate after 1 course of treatment
Defined in accordance with the IWG Response Criteria in AML. Bone marrow blasts<5 percent; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 109/L (1000/µL); platelet count >100 x 109/L (100,000/µL); independence of red cell transfusions.
Complete Remission (CR) Rate after 2 courses of treatment
Defined in accordance with the IWG Response Criteria in AML. Bone marrow blasts<5 percent; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 109/L (1000/µL); platelet count >100 x 109/L (100,000/µL); independence of red cell transfusions.
Overall Response Rate (ORR) after 2 course of treatment
Defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi), or partial response (PR).Biological characteristics exploratory studies were analyzed by single-cell sequencing and Atac-seq. Further, according to European LeukemiaNet risk group, we analyzed the outcomes of patients by molecular subtype as a sub-group analysis.
Rate of Minimal Residual Disease (MRD)-Negative Response
Percentage of participants who achieved MRD-negative response, defined as < 1 leukemia cell per 10,000 leukocytes as assessed by flow cytometry.
Event-free survival
Defined as the time interval from treatment initiation to the occurrence of induction failure,relapse,or death,whichever came first.
Overall Survival (OS)
Defined as the time from joining the clinical study to death due to any cause.
Treatment-related adverse events
Defined as adverse events that occurred from the first dose of study treatment to 30 days after the discontinuation of treatment.
Early death
Defined as death within 30 days of chemotherapy.
Disease-free survival
Defined as the time interval from disease remission to the occurrence of relapse or death,whichever came first.
Full Information
NCT ID
NCT06084819
First Posted
October 10, 2023
Last Updated
October 10, 2023
Sponsor
Chinese PLA General Hospital
Collaborators
The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, The General Hospital of Western Theater Command, The General Hospital of Northern Theater Command, The 960th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Air Force Military Medical University, China, Yantai Yuhuangding Hospital, People's Liberation Army (PLA) Strategic Support Force Characteristic Medical Center, First Hospital of China Medical University
1. Study Identification
Unique Protocol Identification Number
NCT06084819
Brief Title
Clinical Study of Venetoclax Combined With CACAG Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
Official Title
A Prospective,Randomized,and Comparative Study on the Efficacy of Venetoclax Combined With CACAG Regimen and BAT Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2023 (Actual)
Primary Completion Date
January 31, 2026 (Anticipated)
Study Completion Date
January 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese PLA General Hospital
Collaborators
The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, The General Hospital of Western Theater Command, The General Hospital of Northern Theater Command, The 960th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Air Force Military Medical University, China, Yantai Yuhuangding Hospital, People's Liberation Army (PLA) Strategic Support Force Characteristic Medical Center, First Hospital of China Medical University
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
The purpose of this study is to compare the efficacy and safety of venetoclax combined with CACAG regimen with BAT regimen in the treatment of relapsed/refractory acute myeloid leukemia.
Detailed Description
Despite advances in therapies for acute myeloid leukemia (AML) in the past decades, some patients still suffer from relapsed/refractory (R/R) disease, resulting in poor outcomes. With a median overall survival (OS) of 4-7 months under classic chemotherapy approaches, it is imperative to explore new treatment options.Accumulating research has demonstrated the importance of epigenetic modification in the pathogenesis of chemoresistance. Recent studies have shown that combining venetoclax with hypomethylating agents (HMAs) such as azacitidine, or low-dose cytarabine (LDAC) improves the response and survival rates in R/R AML patients. To enhance the response rate, we designed a regimen that combines chidamide, azacitidine, cytarabine, aclarubicin, and G-CSF with venetoclax (CACAG+VEN regimen) for the treatment of patients with R/R AML. In this study, we intend to compare the efficacy and safety of venetoclax combined with the CACAG regimen with Best-Available Therapy(BAT) regimen in the treatment of relapsed/refractory acute myeloid leukemia.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Acute Myeloid Leukemia
Keywords
Relapsed/Refractory Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Venetoclax Combined With CACAG Regimen
Arm Type
Experimental
Arm Description
Venetoclax combined with CACAG regimen for relapsed/refractory AML. Recipients were randomized and those entering the experimental group received azacytidine,cytarabine,aclacinomycin,chidamide,venetoclax and granulocyte colony-stimulating factor. Azacytidine was used as 75 mg/m2/day from day 1 to day 7.Cytarabine was used as 75-100 mg/m2 bid from day 1 to day 5. Aclacinomycin was used as 20 mg/day on days 1,3,5. Chidamide was used as 30 mg/day on days 1,4,8,11. Venetoclax was used as 400 mg/day from day 1 to day 14.Granulocyte colony-stimulating factor was used as 300 ug/day from day 0 until agranulocytosi recovery.
Arm Title
Best-Available Therapy(BAT) Regimen
Arm Type
Active Comparator
Arm Description
BAT regimen for relapsed/refractory AML.Recipients were randomized and those entering this group received FLAG/CLAG/MAE/DCAG/HAA/HAD regimen.
Intervention Type
Drug
Intervention Name(s)
Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor
Other Intervention Name(s)
CACAG+VEN
Intervention Description
Azacytidine (75mg/m2/day, days 1 to 7).
Cytarabine (75-100mg/m2 q12h, days 1 to 5).
Aclacinomycin(20mg/day, days 1,3,5).
Chidamide(30mg/day , days 1,4,8,11).
Venetoclax (100mg on day 1,200mg on day 2,400mg on days 3-14).
Granulocyte colony stimulating factor (300 μg/day, day 0 until agranulocytosis recovery)
Intervention Type
Drug
Intervention Name(s)
Best-Available Therapy(BAT) Regimen
Other Intervention Name(s)
FLAG/CLAG/MAE/DCAG/HAA/HAD Regimen
Intervention Description
FLAG regimen:Fludarabine(30mg/m2,days 1-5)+Cytarabine (1-2g/m2 applied 4h after fludarabine, days 1 to 5)+Granulocyte colony-stimulating factor(300ug/day,days 0 to 5)
CLAG regimen:Cladribine(5mg/2,days 1-5)+Cytarabine (1-2g/m2 applied 4h after fludarabine, days 1 to 5)+Granulocyte colony-stimulating factor(300ug/day,days 0 to 5)
MAE regimen:Mitox(10mg/m2,days 1 to 5)+VP-16(100mg/m2,days 1 to 5)+Cytarabine (100-150mg/m2,days 1 to 7)
DCAG regimen:Decitabine(20mg/m2,days 1 to 5)+Aclacinomycin(20mg/day on days 1,3,5)+Cytarabine (100mg q12h,days 1 to 5)+Granulocyte colony-stimulating factor(300 ug/day,day 0 until agranulocytosi recovery)
HAA regimen:HHT(2mg/m2,days 1 to 7)+Aclacinomycin(20mg/day,days 1 to 7) and Cytarabine (100-200 mg/m2, days 1 to 5);
HAD regimen:HHT(2mg/m2,days 1 to 7)+Daunorubicin(45mg/m2/day,days 1 to 3)+Cytarabine (100-200 mg/m2,days 1 to 5).
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR) after 1 course of treatment
Description
Defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi), or partial response (PR).Biological characteristics exploratory studies were analyzed by single-cell sequencing and Atac-seq. Further, according to European LeukemiaNet risk group, we analyzed the outcomes of patients by molecular subtype as a sub-group analysis.
Time Frame
1 months after the start of study treatment
Secondary Outcome Measure Information:
Title
Complete Remission (CR) Rate after 1 course of treatment
Description
Defined in accordance with the IWG Response Criteria in AML. Bone marrow blasts<5 percent; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 109/L (1000/µL); platelet count >100 x 109/L (100,000/µL); independence of red cell transfusions.
Time Frame
2 months after study treatment
Title
Complete Remission (CR) Rate after 2 courses of treatment
Description
Defined in accordance with the IWG Response Criteria in AML. Bone marrow blasts<5 percent; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 109/L (1000/µL); platelet count >100 x 109/L (100,000/µL); independence of red cell transfusions.
Time Frame
After two courses of chemotherapy (each course is 28 days)
Title
Overall Response Rate (ORR) after 2 course of treatment
Description
Defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi), or partial response (PR).Biological characteristics exploratory studies were analyzed by single-cell sequencing and Atac-seq. Further, according to European LeukemiaNet risk group, we analyzed the outcomes of patients by molecular subtype as a sub-group analysis.
Time Frame
After two courses of chemotherapy (each course is 28 days)
Title
Rate of Minimal Residual Disease (MRD)-Negative Response
Description
Percentage of participants who achieved MRD-negative response, defined as < 1 leukemia cell per 10,000 leukocytes as assessed by flow cytometry.
Time Frame
After two courses of chemotherapy (each course is 28 days)
Title
Event-free survival
Description
Defined as the time interval from treatment initiation to the occurrence of induction failure,relapse,or death,whichever came first.
Time Frame
180 days after study treatment
Title
Overall Survival (OS)
Description
Defined as the time from joining the clinical study to death due to any cause.
Time Frame
180 days after study treatment
Title
Treatment-related adverse events
Description
Defined as adverse events that occurred from the first dose of study treatment to 30 days after the discontinuation of treatment.
Time Frame
From the first dose of study treatment to 30 days after the discontinuation of treatment
Title
Early death
Description
Defined as death within 30 days of chemotherapy.
Time Frame
Within 30 days of the start of the first course of treatment
Title
Disease-free survival
Description
Defined as the time interval from disease remission to the occurrence of relapse or death,whichever came first.
Time Frame
180 days after study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who are able to understand and willing to sign the informed consent form (ICF).
All patients should aged 14 to 75 years,no gender limitation.
Patients with R/R AML, diagnosed in accordance with the 2021 edition of the CMA criteria
Liver function: ALT and AST≤2.5 times the upper limit of normal ,bilirubin≤2 times the upper limit of normal;
Renal function: creatinine ≤the upper limit of normal;
Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness;
The score of Eastern Cooperative Oncology Group (ECOG) is 0-3,and the predicted survival ≥ 4 months.
Patients without severe allergic constitution.
Exclusion Criteria:
Patients with allergy or contraindication to the study drug;
Female patients who are pregnant or breast-feeding.
Patients with a known history of alcohol or drug addiction on the basis that there could be a higher risk of non-compliance to study treatment;
Patients with mental illness or other states unable to comply with the protocol;
Less than 6 weeks after surgical operation of important organs.
Liver function: ALT and AST>2.5 times the upper limit of normal ,bilirubin>2 times the upper limit of normal;Renal function: creatinine >the upper limit of normal;
The patient is not suitable for this clinical trial (poor compliance, substance abuse, etc.)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daihong Liu, doctor
Phone
+8613681171597
Email
daihongrm@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Liping Dou, doctor
Phone
+8613681207138
Email
lipingruirui@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daihong Liu, doctor
Organizational Affiliation
Chinese PLA General Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100853
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daihong Liu, doctor
Phone
86-13681171597
Email
daihongrm@163.com
First Name & Middle Initial & Last Name & Degree
Liping Dou, doctor
Phone
86-13681207138
Email
lipingruirui@163.com
First Name & Middle Initial & Last Name & Degree
Daihong Liu, doctor
12. IPD Sharing Statement
Learn more about this trial
Clinical Study of Venetoclax Combined With CACAG Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
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