Stop Ven-Ipc 2024-001 De-Escalation Study Evaluating Venetoclax and Azacitidine Discontinuation in AML Responding Patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Paoli Calmettes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Feb 2026 → ongoing

Decision date (initial)

2024-11-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French ministry of health, DGOS

External identifiers

EU CT number

2024-514112-28-00

WHO UTN

U1111-1307-4186

ClinicalTrials.gov

NCT06557421

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The main objective is to evaluate the efficacy of VEN-AZA de-escalation strategy by measuring the effect of VEN-AZA discontinuation in term of Disease-Free Survival

Secondary objectives 4

1. To assess the efficacy of VEN-AZA de-escalation strategy by measuring the effect of VEN-AZA discontinuation in term of duration of response, cumulative incidence of relapse, treatment-free remission, overall survival and efficacy of treatment re initiation
2. To assess the adverse-events associated with VEN-AZA de-escalation.
3. To assess quality of life associated with VEN-AZA de-escalation
4. To identify potential predictive factors associated with duration of response and survival after VEN-AZA de-escalation.

Conditions and MedDRA coding

acute myeloid leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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 response defined as complete response (CR) or CR with incomplete hematologic recovery or CR with partial hematologic recovery
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 <2% in the blood)
7. Performance Status <3
8. Females of childbearing potential (FCBP) must have a serum negative pregnancy test at the inclusion assessment. FCBP must also agree to utilize a highly effective method of contraception 6 months after stopping VEN-AZA treatment (according to VEN and AZA SmPCs). Male patients who are sexually active with a FCBP must agree to utilize a highly effective method of contraception 3 months after stopping VEN-AZA treatment (according to VEN and AZA SmPCs)
9. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
10. Affiliated to the French Social Security or beneficiary of such a health Insurance
11. Signed informed consent

Exclusion criteria 7

1. VEN-AZA given as salvage therapy
2. Prior treatment with another drug in addition to VEN-AZA (for instance, triplet therapies with targeted therapies (i.e. IDH or FLT3 inhibitors) or investigational immunotherapy or new agents
3. Participation in a prior investigational study within 30 days prior to ICF’s signature or within 5 half-lives of the investigational product, whichever is longer.
4. Prior allogeneic stem cell transplant
5. Discontinuation of treatment because of absence or loss of response
6. Patient in emergency situation or unable to give consent
7. Severe medical or mental condition precluding the follow up procedures after treatment discontinuation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is 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.

Secondary endpoints 13

1. Absolute duration of hematologic response, defined as the time from inclusion to relapse or death
2. Absolute duration of negative measurable residual disease response, defined as the time from inclusion to measurable residual disease relapse or death
3. Cumulative incidence of relapse, defined as the probability of relapse over time.
4. Treatment-free remission, measured from inclusion to the date of morphologic or MRD relapse, treatment restart or death from any cause, whichever occurs first.
5. Overall survival is defined as the time from inclusion (VEN-AZA de-escalation) to death
6. In case of treatment re initiation, second complete remission, including complete remission/complete remission with incomplete hematologic recovery/complete remission with partial hematologic recovery rates. The time to remission will also be analyzed (defined as the time between date of treatment re initiation and complete remission)
7. To assess quality of life: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire QLQ-C30
8. Hospitalization rate
9. Transfusions
10. Grade 3-4 adverse events (CTCAE v5.0)
11. To identify potential predictive factors associated with duration of response and survival after VEN-AZA de-escalation, age will be analyzed
12. To identify potential predictive factors associated with duration of response and survival after VEN-AZA de-escalation, cytogenetic and molecular alterations assessment following ELN 2022 classification will be analyzed
13. To identify potential predictive factors associated with duration of response and survival after VEN-AZA de-escalation, number of prior VEN-AZA cycles will be analyzed

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Paoli Calmettes

Sponsor organisation

Institut Paoli Calmettes

Address

232 Boulevard De Sainte Marguerite, Bp 156 Bp 156

City

Marseille

Postcode

13009

Country

France

Scientific contact point

Organisation

Institut Paoli Calmettes

Contact name

GARCIAZ Sylvain

Public contact point

Organisation

Institut Paoli Calmettes

Contact name

LAROSA Marina

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications