Azacitidine for Acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- Subject must have confirmation of AML by WHO 2022 criteria and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age or co-morbidities.\n- Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.\n- Patients must be affiliated to a social security system or beneficiary of the same (only for France)\n- Patients shall be eligible to undergo Azacitidine and Venetoclax treatment and BM aspiration. Patients who do not consent to a BM aspiration will not be eligible (diagnosis and follow –up)\n- Subject must be ≥ 60 years of age.\n- Subject must have a projected life expectancy of at least 12 weeks.\n- Subject must be considered ineligible for induction therapy defined by the following:≥ 75 years of age OR ≥ 60 to 74 years of age with at least one of the following co-morbidities: •\tECOG Performance Status of 2 or 3; •\tCardiac history of CHF requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina; •\tDLCO ≤ 65% or FEV1 ≤ 65%; •\tSevere Renal impairement: Creatinine clearance ≥ 30 mL/min to < 45 ml/min •\tModerate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × ULN •\tAny other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the coordinator before study enrollment\n- Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status (Appendix 4): •\t0 to 2 for subject ≥ 75 years of age. •\t0 to 3 for subject ≥ 60 to 74 years of age.\n- Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula.\n- Subject must have adequate liver function as demonstrated by: •\tAspartate aminotransferase (AST) ≤ 3.0 × ULN* •\talanine aminotransferase (ALT) ≤ 3.0 × ULN* •\tbilirubin ≤ 1.5 × ULN* * Unless considered to be due to leukemic organ involvement. Subjects who are < 75 years of age may have a bilirubin of ≤ 3.0 × ULN\n- Female subjects must be either postmenopausal (amenorrhea for at least 12 months with no alternative medical reasons) or surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).\n- Non-sterile male subjects must use contraceptive methods with partner(s) prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug."}

Exclusion criteria

• {"criterion_text":"- Subject has received treatment with the following: -\tHypomethylating agent, venetoclax and/or any chemo-therapeutic agent for Myelodysplastic syndrome (MDS). -\tChimeric Antigen Receptor (CAR)-T cell therapy. -\tExperimental therapies for MDS or Acute Myeloid Leukemia (AML). -\tCurrent participation in another research or observational study\n- Subject has acute promyelocytic leukemia\n- Subject has known active CNS involvement with AML.\n- Known human immunodeficiency virus HIV\n- Known hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months.\n- Subject has a cardiovascular disability status of New York Heart Association Class ≥ 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.\n- Subject has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study.\n- NB: patients with IDH1-mutant AML will not be formally excluded from the study. However, investigators are strongly encouraged to prefer treatment combining Azacitidine and Ivosidenib (AGILE phase III trial).\n- Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.\n- Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).\n- Subject has a history of other malignancies prior to study entry, with the exception of: •\tAdequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;•\tBasal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; •\tPrevious malignancy confined and surgically resected (or treated with other modalities) with curative intent and considered in remission for 3 years.\n- Subject has a white blood cell count > 25 × 109/L. (Hydroxyurea is permitted to meet this criterion.)\n- Subject has hypersensitivity to the active substances of any of the excipients\n- Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.\n- Subject has history of myeloproliferative neoplasm [MPN], including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.\n- Subject has favorable risk cytogenetics such as t(8;21), inv(16), t(16;16) or t(15;17) as per the NCCN Guidelines Version 2, 2016 for Acute Myeloid Leukemia."}

Primary endpoints

• {"endpoint_text":"- The proportion of subjects with complete remission or complete remission with incomplete marrow recovery (CR/CRi) will be calculated based on current IWG criteria for AML (Cheson et al J Clin Oncol 2003)","definition_or_measurement_approach":"Calculated based on current IWG criteria for AML (Cheson et al J Clin Oncol 2003)."}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS). Event-Free Survival (EFS).","definition_or_measurement_approach":"Time-to-event measures: overall survival and event-free survival as standard survival endpoints (time from randomization to death for OS; to defined events for EFS)."}
• {"endpoint_text":"- Early mortality rate at Day 60.","definition_or_measurement_approach":"Proportion of subjects who die by Day 60."}
• {"endpoint_text":"- Time to first response. Time to best response.","definition_or_measurement_approach":"Time from treatment start to first documented response and to best observed response."}
• {"endpoint_text":"- Duration of response (DoR).","definition_or_measurement_approach":"Time from first documented response to relapse or death (standard DoR definition)."}
• {"endpoint_text":"- Health-Related Quality of Life (HRQoL) assessed by the EORTC QLQ-ELD14 and EuroQol EQ-5D-5L questionnaires","definition_or_measurement_approach":"Patient-reported outcomes measured using EORTC QLQ-ELD14 and EQ-5D-5L instruments."}
• {"endpoint_text":"- Scheme modification will be defined as the proportion of CR/CRi patients that presented treatment modification not authorized by protocol as VEN schedule modification (dose, duration), delay >2 days from the initial Day of the subsequent cycle and/or temporary/definitive VEN discontinuation.","definition_or_measurement_approach":"Proportion of CR/CRi patients with unauthorized venetoclax schedule modifications, delays >2 days, or VEN discontinuation as defined."}
• {"endpoint_text":"- Toxicity evaluated by platelet transfusion, febrile neutropenia or severe infection episodes, hospitalization requirement and hospitalization length stay","definition_or_measurement_approach":"Toxicity metrics include need for platelet transfusion, episodes of febrile neutropenia or severe infection, hospitalization incidence and length of hospital stay."}
• {"endpoint_text":"- Incremental costs and QALY and ICER (€/QALY) (only for included patients treated in France)","definition_or_measurement_approach":"Health economic evaluation measuring incremental costs, QALYs and ICER (€/QALY) for patients treated in France."}

France

Earliest CTIS Part Ii Submission Date

10-12-2025

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

63

Number Of Sites

10

Number Of Participants

131

Spain

Earliest CTIS Part Ii Submission Date

08-01-2026

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

89

Number Of Sites

12

Number Of Participants

131

Primary sponsor

Full Name

Institut Gustave Roussy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France