Clinical trial NCT06557421: De-Escalation Study Evaluating Venetoclax and Azacitidine Discontinuation in AML Responding Patients
Official title: De-Escalation Study Evaluating Venetoclax and Azacitidine Discontinuation in AML Responding Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: Institut Paoli-Calmettes
Sponsor class: OTHER
First posted: 2024-08-16
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


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.

Primary outcomes:
measure: 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.
timeFrame: 24 months
Secondary outcomes:
measure: Absolute duration of hematologic response, defined as the time from inclusion to relapse or death.
timeFrame: 24 months
measure: Absolute duration of negative measurable residual disease response, defined as the time from inclusion to measurable residual disease relapse or death.
timeFrame: 24 months
measure: Cumulative incidence of relapse, defined as the probability of relapse over time.
timeFrame: 24 months
measure: Overall survival, defined as the time from inclusion (VEN-AZA de-escalation) to death.
timeFrame: 24 months
measure: Second complete remission occurence.
timeFrame: 24 months
measure: Time to second remission, defined as the time between date of treatment re initiation and complete remission.
timeFrame: 24 months
measure: Hospitalization rate associated with VEN-AZA de-escalation.
timeFrame: 24 months
measure: Transfusion occurrence associated with VEN-AZA de-escalation.
timeFrame: 24 months
measure: Grade 3-4 adverse events occurence associated with VEN-AZA de-escalation.
timeFrame: 24 months
measure: Correlation between age and duration of response and survival after VEN-AZA de-escalation.
timeFrame: 24 months
measure: Correlation between FAB classification and duration of response and survival after VEN-AZA de-escalation.
timeFrame: 24 months
measure: Correlation between cytogenetic and molecular alterations and duration of response and survival after VEN-AZA de-escalation.
timeFrame: 24 months
measure: Correlation between number of prior VEN-AZA cycles and duration of response and survival after VEN-AZA de-escalation.
timeFrame: 24 months
Other outcomes:
Locations:
city: Marseille
country: France
facility: Institut Paoli-Calmettes
Study officials:
affiliation: Institut Paoli-Calmettes
name: Sylvain GARCIAZ, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: