Combination of Venetoclax, Hypomethylation Agent and Low-dose Cytarabine as a Salvage Therapy for Acute Myeloid Leukemia
Primary Purpose
Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Minimal Residual Disease
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Venetoclax, Decitabine, Azacytidine, Cytarabine
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed Acute Myeloid Leukemia focused on measuring Venetoclax, Hypomethylation agent, Cytarabine
Eligibility Criteria
Inclusion Criteria:
- Aged ≥18 years old, voluntarily participate in clinical research and sign an informed consent form and be willing to follow and be able to complete all experimental procedures.
- The toxic and side effects caused by the last treatment should be recovered.
- Eastern Cooperative Oncology Group score of 0 to 3 points.
The organ function is intact.
- Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5×ULN (Upper Limit of Normal).
- Creatinine≤1.5×ULN.
- Bilirubin≤1.5×ULN.
- Karnofsky≥70.
- The expected survival period is at least 12 weeks.
- Non-pregnant, non-breastfeeding women.
Exclusion Criteria:
- Suffering from other untreated or unrelieved malignant tumors within 2 years.
- Major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and experimental therapy were performed within 2 weeks of the first medication.
- Suffering from any other known serious and/or uncontrolled disease (eg, uncontrolled diabetes; cardiovascular disease, including congestive heart failure New York Heart Association [NYHA] Class III or IV, 6 months patients with myocardial infarction and poorly controlled blood pressure); chronic renal failure; or active uncontrolled infection); the investigators considered unsuitable for this clinical trial.
- Patients who are unwilling or unable to comply with the protocol.
- Currently being treated with other systemic anti-tumor or anti-tumor research drugs.
- Women who are pregnant or breastfeeding.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
venetoclax + Hypomethylation agent + low-dose cytarabine treatment group
Arm Description
patients treated with venetoclax combined with decitabine/azacytidine and low-dose cytarabine
Outcomes
Primary Outcome Measures
Complete remission rate
percentage of subjects with complete remission (CR) and incomplete hematologic recovery (CRi)
Complete minimal residual disease (MRD) Response Rate
Percentage of subjects with MRD negative or MRD < 0.01%
MRD Response Rate
Percentage of subjects with MRD < 0.1% detectable by multicolor flow cytometry
Secondary Outcome Measures
Relapse-Free Survival
Time interval from leukemia free state to the first recurrence or death
Overall Survival
Time interval from start of treatment until death or last follow-up
Duration of response
Time interval from morphologic/MRD response to loss of response or death
Adverse events
Number of subjects with adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05362942
Brief Title
Combination of Venetoclax, Hypomethylation Agent and Low-dose Cytarabine as a Salvage Therapy for Acute Myeloid Leukemia
Official Title
A Study of Combination of Venetoclax, Hypomethylation Agent and Low-dose Cytarabine as a Salvage Therapy in Patients With Acute Myeloid Leukemia Who Had Relapsed/Refractory Disease or Positive Minimal Residual Disease
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 1, 2022 (Anticipated)
Primary Completion Date
April 30, 2023 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing 302 Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Although studies are ongoing to evaluate the efficiency and safety of venetoclax-based therapy, alone or in combination with hypomethylation agent or low-dose cytarabine, in relapsed/refractory acute myeloid leukemia, data are scarce and heterogenous. In this study, the investigators aimed to assess safety and response to a new venetoclax-based triple-drug combination regimen (venetoclax + hypomethylation agent + low-dose cytarabine) in acute myeloid leukemia patients who had relapsed/refractory disease or positive minimal residual disease.
Detailed Description
Although the promising activity of venetoclax-based therapy is well demonstrated in the treatment of previously untreated elderly or unfit patients with acute myeloid leukemia, there are few data on the efficacy of venetoclax-based salvage therapy in relapsed/refractory patients, which can be difficult to treat. To date, data on venetoclax as monotherapy or in combination with hypomethylation agent or low-dose cytarabine as a salvage regimen in relapsed/refractory AML are scarce and heterogenous. In this study, the investigators aimed to assess safety and efficiency of a new triple-drug combination regimen, venetoclax + hypomethylation agent + low-dose cytarabine, in patients with relapsed/refractory acute myeloid leukemia or persistent positive minimal residual disease in the salvage setting.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Minimal Residual Disease
Keywords
Venetoclax, Hypomethylation agent, Cytarabine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
venetoclax + Hypomethylation agent + low-dose cytarabine treatment group
Arm Type
Experimental
Arm Description
patients treated with venetoclax combined with decitabine/azacytidine and low-dose cytarabine
Intervention Type
Drug
Intervention Name(s)
Venetoclax, Decitabine, Azacytidine, Cytarabine
Other Intervention Name(s)
Venetoclax (ABT-199, GDC-0199), Decitabine (Dacogen, 5-aza-2-deoxycytidine), Azacitidine (5-Azacytidine, Ladakamycin), Cytarabine (Cytarabine hydrochloride)
Intervention Description
Venetoclax was given at a dose of 400 mg/day for 28 days per cycle. Decitabine was given at a dose of 20 mg/m2/day for 5 days (n=3) or azacytidine (n=8) was given at a dose of 75 mg/m2/day for 7 days at the discretion of the treating physician. Cytarabine was given at a dose of 10 mg/m2 twice daily for 7 days.
Primary Outcome Measure Information:
Title
Complete remission rate
Description
percentage of subjects with complete remission (CR) and incomplete hematologic recovery (CRi)
Time Frame
At the end of Cycle 2 (each cycle is 28 days)
Title
Complete minimal residual disease (MRD) Response Rate
Description
Percentage of subjects with MRD negative or MRD < 0.01%
Time Frame
At the end of Cycle 2 (each cycle is 28 days)
Title
MRD Response Rate
Description
Percentage of subjects with MRD < 0.1% detectable by multicolor flow cytometry
Time Frame
At the end of Cycle 2 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Relapse-Free Survival
Description
Time interval from leukemia free state to the first recurrence or death
Time Frame
24 months
Title
Overall Survival
Description
Time interval from start of treatment until death or last follow-up
Time Frame
24 months
Title
Duration of response
Description
Time interval from morphologic/MRD response to loss of response or death
Time Frame
24 months
Title
Adverse events
Description
Number of subjects with adverse events
Time Frame
start of treatment to 2 weeks after end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged ≥18 years old, voluntarily participate in clinical research and sign an informed consent form and be willing to follow and be able to complete all experimental procedures.
The toxic and side effects caused by the last treatment should be recovered.
Eastern Cooperative Oncology Group score of 0 to 3 points.
The organ function is intact.
Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5×ULN (Upper Limit of Normal).
Creatinine≤1.5×ULN.
Bilirubin≤1.5×ULN.
Karnofsky≥70.
The expected survival period is at least 12 weeks.
Non-pregnant, non-breastfeeding women.
Exclusion Criteria:
Suffering from other untreated or unrelieved malignant tumors within 2 years.
Major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and experimental therapy were performed within 2 weeks of the first medication.
Suffering from any other known serious and/or uncontrolled disease (eg, uncontrolled diabetes; cardiovascular disease, including congestive heart failure New York Heart Association [NYHA] Class III or IV, 6 months patients with myocardial infarction and poorly controlled blood pressure); chronic renal failure; or active uncontrolled infection); the investigators considered unsuitable for this clinical trial.
Patients who are unwilling or unable to comply with the protocol.
Currently being treated with other systemic anti-tumor or anti-tumor research drugs.
Women who are pregnant or breastfeeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiao-ning Gao
Phone
+861066947169
Email
gaoxn@263.net
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Xu
Phone
+861066947174
Email
xulei800@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiao-ning Gao
Organizational Affiliation
Chinese PLA General Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Combination of Venetoclax, Hypomethylation Agent and Low-dose Cytarabine as a Salvage Therapy for Acute Myeloid Leukemia
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