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

NCT05361057 | Terminated Phase 2

• 1 other identifier: IIT2022006
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Measurable Disease; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• relapse free survival

  survival from the preemptive therapy to relapse

  6 months

Secondary Outcomes (3)

• major response

  3 months

• overall survival

  1 year

• relapse free survival

  12 months

Study Arms (2)

venetoclax pluse azacitidine arm

EXPERIMENTAL

azacytidine 75 mg/m2 d1-7，venetoclax: 100mg d1, 200mg d2, 400mg d3-21

Drug: Venetoclax, Azacitidine

venetoclax pluse DA arm

ACTIVE COMPARATOR

daunorubicin：45mg/m2 d1-2, cytarabine:100mg/ m2 d1-5, venetoclax: 100mg d1, 200mg d2, 400mg d3-14

Drug: Venetoclax, daunorubicin, cytarabine

Interventions

Venetoclax, Azacitidine DRUG

The patients were administrated with azacytidine 75 mg/m2 d1-7，venetoclax: 100mg d1, 200mg d2, 400mg d3-21;

venetoclax pluse azacitidine arm

Venetoclax, daunorubicin, cytarabine DRUG

The patients were administrated with daunorubicin：45mg/m2 d1-2, cytarabine:100mg/ m2 d1-5, venetoclax: 100mg d1, 200mg d2, 400mg d3-14

venetoclax pluse DA arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed acute myeloid leukemia
• Received chemotherapy within 24 months and has completed the consolidation treatment plan
• In complete remission
• 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%.
• Age≥ 18 years #male or female
• ECOG-PS score 0-2
• 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#
• Written informed consent

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (1)

HBDH

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine; Daunorubicin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Arabinonucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2022
• First Posted: May 4, 2022
• Study Start: June 29, 2022
• Primary Completion: February 28, 2023
• Study Completion: January 23, 2024
• Last Updated: December 5, 2025

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)