Venetoclax for Acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- Female/Male ≥ 18 years of age\n- Affiliated to the French Social Security or beneficiary of such a health Insurance\n- Signed informed consent\n- Diagnosis of previously untreated AML according to the 2022 International Consensus Classification of Myeloid Neoplasms and Acute Leukemias\n- VEN-AZA given as first-line treatment\n- Duration of VEN-AZA therapy of 12 months (+/- 28 days), regardless of duration of VEN-AZA cycles and the doses\n- Patients in first composite complete response defined as complete response (CR) or CR with incomplete hematologic recovery or CR with partial hematologic recovery\n- 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)\n- Performance Status <3\n- 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)\n- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule"}

Exclusion criteria

• {"criterion_text":"- VEN-AZA given as salvage therapy\n- 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\n- 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.\n- Prior allogeneic stem cell transplant\n- Discontinuation of treatment because of absence or loss of response\n- Patient in emergency situation or unable to give consent\n- Severe medical or mental condition precluding the follow up procedures after treatment discontinuation"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"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

• {"endpoint_text":"- Absolute duration of hematologic response, defined as the time from inclusion to relapse or death","definition_or_measurement_approach":"Defined as the time from inclusion to relapse or death."}
• {"endpoint_text":"- Absolute duration of negative measurable residual disease response, defined as the time from inclusion to measurable residual disease relapse or death","definition_or_measurement_approach":"Defined as the time from inclusion to measurable residual disease relapse or death."}
• {"endpoint_text":"- Cumulative incidence of relapse, defined as the probability of relapse over time.","definition_or_measurement_approach":"Defined as the probability of relapse over time."}
• {"endpoint_text":"- Treatment-free remission, measured from inclusion to the date of morphologic or MRD relapse, treatment restart or death from any cause, whichever occurs first.","definition_or_measurement_approach":"Measured from inclusion to the date of morphologic or MRD relapse, treatment restart or death from any cause, whichever occurs first."}
• {"endpoint_text":"- Overall survival is defined as the time from inclusion (VEN-AZA de-escalation) to death","definition_or_measurement_approach":"Defined as the time from inclusion to death."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Rates of second complete remission (CR/CRi/CRh) after treatment re-initiation; time to remission defined as time between date of treatment re-initiation and complete remission."}
• {"endpoint_text":"- To assess quality of life: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire QLQ-C30","definition_or_measurement_approach":"Quality of life measured using the EORTC QLQ-C30 questionnaire."}
• {"endpoint_text":"- Hospitalization rate","definition_or_measurement_approach":"Rate of hospitalizations (definition not further specified in available text)."}
• {"endpoint_text":"- Transfusions","definition_or_measurement_approach":"Incidence or number of transfusions (definition not further specified in available text)."}
• {"endpoint_text":"- Grade 3-4 adverse events (CTCAE v5.0)","definition_or_measurement_approach":"Adverse events graded using CTCAE v5.0; report grade 3-4 events."}
• {"endpoint_text":"- To identify potential predictive factors associated with duration of response and survival after VEN-AZA de-escalation, age will be analyzed","definition_or_measurement_approach":"Age will be analyzed as a potential predictive factor for duration of response and survival."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Cytogenetic and molecular alterations will be assessed according to ELN 2022 classification as predictive factors."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Number of prior VEN-AZA cycles will be analyzed as a predictive factor."}

France

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

04-03-2026

Processing Time Days

492

Number Of Sites

5

Number Of Participants

50

Primary sponsor

Full Name

Institut Paoli Calmettes

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"French ministry of health, DGOS","duties_or_roles":"Source of monetary support","organisation_type":"Government"}