Stopping venetoclax plus azacitidine after about 12 months in AML responders

De-Escalation Study Evaluating Venetoclax and Azacitidine Discontinuation in AML Responding Patients

This trial will test whether stopping venetoclax plus azacitidine after about 12 months keeps adults with AML who are in remission and MRD-negative disease-free and safe.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institut Paoli-Calmettes (Academic / other)
• Locations: 1 site (Marseille)
• Trial ID: NCT06557421 on ClinicalTrials.gov

What this trial studies

This phase 2 interventional study enrolls adults with previously untreated AML who received first-line venetoclax plus azacitidine for roughly 12 months and achieved a first composite complete remission with no detectable MRD. Enrolled patients will discontinue venetoclax–azacitidine and undergo close, regular monitoring for disease recurrence, with the primary endpoint focused on disease-free survival after treatment stop. Results from the prospective cohort will be compared to a retrospectively selected cohort with identical eligibility to contextualize outcomes, and additional efficacy and safety measures will be recorded. The study aims to determine whether therapy de-escalation can reduce treatment burden without compromising leukemia control.

Who should consider this trial

Good fit: Adults (≥18) with previously untreated AML who received first-line venetoclax plus azacitidine for about 12 months, achieved CR/CRi/CRh, are locally MRD-negative, and have ECOG performance status <3.

Not a fit: Patients who remain MRD-positive, are not in first composite remission, received prior non–venetoclax/azacitidine therapies, or cannot commit to close follow-up are unlikely to benefit from this de-escalation strategy.

Why it matters

Potential benefit: If successful, this approach could allow some patients to stop long-term venetoclax–azacitidine, reducing side effects and treatment burden while maintaining remission.

How similar studies have performed: Small retrospective reports and subgroup analyses have suggested stopping therapy in select MRD-negative AML patients may be feasible, but prospective evidence is still limited.

Eligibility criteria

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.

Where this trial is running

Marseille

• Institut Paoli-Calmettes — Marseille, France (Recruiting)

Study contacts

• Principal investigator: Sylvain GARCIAZ, MD PhD — Institut Paoli-Calmettes
• Study coordinator: Jihane PAKRADOUNI, PharmD,PhD

Conditions Acute Myeloid Leukemia