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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
Beijing 302 Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed Acute Myeloid Leukemia focused on measuring Venetoclax, Hypomethylation agent, Cytarabine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. 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.
  2. The toxic and side effects caused by the last treatment should be recovered.
  3. Eastern Cooperative Oncology Group score of 0 to 3 points.
  4. 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.
  5. Karnofsky≥70.
  6. The expected survival period is at least 12 weeks.
  7. Non-pregnant, non-breastfeeding women.

Exclusion Criteria:

  1. Suffering from other untreated or unrelieved malignant tumors within 2 years.
  2. Major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and experimental therapy were performed within 2 weeks of the first medication.
  3. 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.
  4. Patients who are unwilling or unable to comply with the protocol.
  5. Currently being treated with other systemic anti-tumor or anti-tumor research drugs.
  6. 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

    First Posted
    April 20, 2022
    Last Updated
    May 4, 2022
    Sponsor
    Beijing 302 Hospital
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    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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