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

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

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

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Measurable Disease
• Intervention / Treatment: Drug: Venetoclax, Azacitidine; Drug: Venetoclax, daunorubicin, cytarabine

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • HBDH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relapse free survival	survival from the preemptive therapy to relapse	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major response	The MRD level turns negative or the specific value decreases by 1 order of magnitude	3 months
overall survival	duration from enrollment to death or loss of followup	1 year
relapse free survival	survival from the preemptive therapy to relapse	12 months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2022
• Primary Completion (Actual): February 28, 2023
• Study Completion (Actual): January 23, 2024

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 28, 2025
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Aminoglycosides; Cytarabine; Azacitidine; Daunorubicin; venetoclax
• Other Study ID Numbers: IIT2022006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No