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Efficacy of Venetoclax Based Regimen in Prevention Relapse of Consecutive MRD Positive AML Patients

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ClinicalTrials.gov Identifier: NCT05361057
Recruitment Status : Recruiting
First Posted : May 4, 2022
Last Update Posted : May 4, 2022
Sponsor:
Information provided by (Responsible Party):
Institute of Hematology & Blood Diseases Hospital

Brief Summary:
Measurable disease (MRD) plays an important role in the therapeutic efficacy and prognosis of acute myeloid leukemia (AML). Studies show that persistent MRD positivity after induction indicates that the patient has a higher risk of recurrence. Even if the patient is assessed as a low risk group, once there is persistent MRD positive, Allogeneic hematopoietic stem cell transplantation (allo HSCT) or clinical trials should be considered to improve the overall survival of patients. However, some patients cannot accept allo HSCT due to economic reasons or lack of suitable donors. How to prolong the recurrence free survival of these patients is still a great challenge. Platzbecker et al. applied azacytidine (AZA) monotherapy to AML patients with continuous MRD positive after combined chemotherapy. The results showed that the preemptive treatment of AZA could prevent or significantly delay the hematological relapse of MDS or AML patients with MRD positive. In addition, the application of venetoclax has significantly changed the therapeutic prospect of AML and provided new opportunities. Studies have shown that venetoclax can enhance the activity of anti HMA, cytarabine, idarubicin and other drugs. The curative effect of venetoclax combined with AZA in the treatment of elderly AML patients who are not suitable for intensive treatment is better than that of single AZA regimen, and the negative rate of MRD after induction treatment of venetoclax combined with HMA is higher (54-81%). Therefore, the investigators believe that for patients who continue to be MRD positive after induction and consolidation treatment, venetoclax based regimen may be an effective preemptive treatment regimen, which can prolong the relapse free time and overall survival of these patients

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Measurable Disease Drug: Venetoclax, Azacitidine Drug: Venetoclax, daunorubicin, cytarabine Phase 2

Detailed Description:

In the study, 40 patients will be enrolled and treated with venotoclax combined AZA and DA regimen. Patients receive major response will be given venotoclax combined AZA regimen as maintenance treatment. The primary endpoint was 6 month relapse-free survival. Measurable residual disease (MRD) will be detected at the beginning of the therapy and after the therapy. The adverse effect will also be explored.

Preemptive chemotherapy: regimen 1: azacytidine 75 mg/m2 d1-7,venetoclax: 100mg d1, 200mg d2, 400mg d3-21; regimen 2: daunorubicin:45mg/m2 d1-2, cytarabine:100mg/ m2 d1-5, venetoclax: 100mg d1, 200mg d2, 400mg d3-14; maintenance therapy: patient in regimen 1 group: azacytidine 75 mg/m2 d1-7,venetoclax: 400mg d1-14, for 4 cycles, patients in regimen 2 group: azacytidine 75 mg/m2 d1-7,venetoclax: 400mg d1-14, for 4 cycles.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Single Arm, Multicenter Clinical Study to Evaluate the Efficacy of Venetoclax Combined With Azacytidine or DA Regimen in Prevention the Relapse of Consecutive MRD Positive AML Patients
Estimated Study Start Date : May 1, 2022
Estimated Primary Completion Date : February 28, 2023
Estimated Study Completion Date : August 31, 2023


Arm Intervention/treatment
Experimental: venetoclax pluse azacitidine arm
azacytidine 75 mg/m2 d1-7,venetoclax: 100mg d1, 200mg d2, 400mg d3-21
Drug: Venetoclax, Azacitidine
The patients were administrated with azacytidine 75 mg/m2 d1-7,venetoclax: 100mg d1, 200mg d2, 400mg d3-21;

Active Comparator: venetoclax pluse DA arm
daunorubicin:45mg/m2 d1-2, cytarabine:100mg/ m2 d1-5, venetoclax: 100mg d1, 200mg d2, 400mg d3-14
Drug: Venetoclax, daunorubicin, cytarabine
The patients were administrated with daunorubicin:45mg/m2 d1-2, cytarabine:100mg/ m2 d1-5, venetoclax: 100mg d1, 200mg d2, 400mg d3-14




Primary Outcome Measures :
  1. relapse free survival [ Time Frame: 6 months ]
    survival from the preemptive therapy to relapse


Secondary Outcome Measures :
  1. major response [ Time Frame: 3 months ]
    The MRD level turns negative or the specific value decreases by 1 order of magnitude

  2. overall survival [ Time Frame: 1 year ]
    duration from enrollment to death or loss of followup

  3. relapse free survival [ Time Frame: 12 months ]
    survival from the preemptive therapy to relapse



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosed acute myeloid leukemia
  2. Received chemotherapy within 24 months and has completed the consolidation treatment plan
  3. In complete remission
  4. With MRD positive: abnormal myeloid cells in bone marrow ≥ 0.1%, or NPM1 gene mutation and other fusion gene positive(RUNX 1-RUNX1T 1、CBFB-MYH11 and DEK-NUP214), the PCR quantification ≥1%.
  5. Age≥ 18 years #male or female
  6. ECOG-PS score 0-2
  7. Aboratory tests#within 7 days before chemotherapy# 1). Serum total bilirubin≤1.5xULN# 2). Serum AST and ALT≤2.5xULN 3). Serum creatinine≤2xULN# 4). Cardiac enzymes≤2xULN 5). Ejection fraction >50% by ECHO#
  8. Written informed consent

Exclusion Criteria:

  1. Hematological relapse (the proportion of blast cells in bone marrow is greater than 5%)
  2. Receive hematopoietic stem cell transplantation within 4 weeks
  3. APL
  4. Have been treated with venetoclax in the past 6 months (who can be enrolled after stopping for more than 6 months)
  5. Suffering from malignant tumors of other organs (those requiring treatment)
  6. Pregnant or lactating women
  7. Active heart diseases
  8. Severe active infection
  9. Unfit for enrollment evaluated by investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05361057


Locations
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China, Tianjin
HBDH Recruiting
Tianjin, Tianjin, China, 300020
Contact: Hui Wei    +862223909020    weihui@ihcams.ac.cn   
Sponsors and Collaborators
Institute of Hematology & Blood Diseases Hospital
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Responsible Party: Institute of Hematology & Blood Diseases Hospital
ClinicalTrials.gov Identifier: NCT05361057    
Other Study ID Numbers: IIT2022006-EC-1
First Posted: May 4, 2022    Key Record Dates
Last Update Posted: May 4, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cytarabine
Azacitidine
Daunorubicin
Venetoclax
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors