De-Escalation Study Evaluating Venetoclax and Azacitidine Discontinuation in AML Responding Patients (STOP VEN)

The goal of this clinical trial is to test efficacy and safety of a VENETOCLAX-AZACITIDINE (VEN-AZA) de-escalation strategy in Acute Myeloid Leukemia responding patients. The main objectives of the study are:

• Evaluation of the efficacy of VEN-AZA de-escalation strategy by measuring the effect of VEN-AZA discontinuation in term of Disease-Free Survival.
• Evaluation of the other efficacy parameters and safety of VEN-AZA de-escalation strategy.

Patients from the prospective study will be compared to a retrospective cohort of patients who will be selected on the basis of identical eligibility criteria.

Participants will:

• Stop VEN-DASA treatment
• Be closely monitored by regular evaluation of the disease

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax; Drug: Azacitidine

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jihane PAKRADOUNI, PharmD,PhD; Phone Number: +33491223778; Email: drci.up@ipc.unicancer.fr
• Study Contact Backup: Name: Laurie-Anne GOUTY, PhD; Phone Number: 33491223778; Email: drci.up@ipc.unicancer.fr

Study Locations

• France
  • Marseille, France, 13273
    • Recruiting
    • Institut Paoli-Calmettes
    • Contact: Jihane PAKRADOUNI, PharmD, PhD; Phone Number: 33491223778; Email: drci.up@ipc.unicancer.fr
    • Contact: Laurie-Anne GOUTY, PhD; Phone Number: 33491223778; Email: drci.up@ipc.unicancer.fr
    • Principal Investigator: Sylvain GARCIAZ, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female/Male ≥ 18 years of age;
2. Diagnosis of previously untreated AML according to the 2022 International Consensus Classification of Myeloid Neoplasms and Acute Leukemias;
3. VEN-AZA given as first-line treatment;
4. Duration of VEN-AZA therapy of 12 months (+/- 28 days), regardless of duration of VEN-AZA cycles and the doses;
5. Patients in first composite complete remission (CRc) defined as complete remission (CR) or CR with incomplete hematologic recovery (CRi) or CR with partial hematologic recovery (CRh);
6. Absence of detectable minimal residual disease (MRD) performed locally (i.e. MRDneg defined as MCF MRD <0.1% of CD45 expressing cells with the target immunophenotype in bone marrow, or NPM1 or RUNX1-RUNX1T1 or CBFB-MYH11 MRD copy numbers <0.1% in the blood);
7. ECOG <3;
8. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
9. Affiliated to the French Social Security or beneficiary of such a health Insurance;
10. Signed informed consent.

Non inclusion Criteria:

1. VEN-AZA given as salvage therapy;
2. Prior allogeneic stem cell transplant;
3. Discontinuation of treatment because of absence or loss of response;
4. Patient in emergency situation or unable to give consent;
5. Severe medical or mental condition precluding the follow up procedures after treatment discontinuation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VEN-AZA de-escalation	Drug: Venetoclax; complete discontinuation of Venetoclax; Drug: Azacitidine; complete discontinuation of Azacitidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease-Free Survival, measured from inclusion (VEN-AZA de-escalation) to the date of morphologic or measurable residual disease relapse or death from any cause, whichever occurs first.	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Absolute duration of hematologic response, defined as the time from inclusion to relapse or death.	24 months
Absolute duration of negative measurable residual disease response, defined as the time from inclusion to measurable residual disease relapse or death.	24 months
Cumulative incidence of relapse, defined as the probability of relapse over time.	24 months
Overall survival, defined as the time from inclusion (VEN-AZA de-escalation) to death.	24 months
Second complete remission occurence.	24 months
Time to second remission, defined as the time between date of treatment re initiation and complete remission.	24 months
Hospitalization rate associated with VEN-AZA de-escalation.	24 months
Transfusion occurrence associated with VEN-AZA de-escalation.	24 months
Grade 3-4 adverse events occurence associated with VEN-AZA de-escalation.	24 months
Correlation between age and duration of response and survival after VEN-AZA de-escalation.	24 months
Correlation between FAB classification and duration of response and survival after VEN-AZA de-escalation.	24 months
Correlation between cytogenetic and molecular alterations and duration of response and survival after VEN-AZA de-escalation.	24 months
Correlation between number of prior VEN-AZA cycles and duration of response and survival after VEN-AZA de-escalation.	24 months

Collaborators and Investigators

• Sponsor: Institut Paoli-Calmettes
• Investigators: Principal Investigator: Sylvain GARCIAZ, MD PhD, Institut Paoli-Calmettes

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: August 9, 2024
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

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; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax
• Other Study ID Numbers: STOP VEN-IPC 2024-001

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