A Randomized, Open-labelled, Multicenter Trial Evaluating Efficacy and Safety of A Reduced Venetoclax Exposure To Seven Days Versus Standard Continuous Venetoclax Exposure Combined With Azacitidine in Treatment Naïve Subjects with Acute Myeloid Leukemia Who Are Ineligible for Intensive Induction (SEVENAZA)
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase III
PATOLOGÍA
Leucemia linfática crónica y otros SLPC, Leucemia mieloide aguda, Linfoma, Leucemia
CENTRO INVESTIGADOR
H. Fundación Jiménez Díaz
INVESTIGADOR PRINCIPAL
José Luis LOPEZ LORENZO
CENTRO INVESTIGADOR
H.U. 12 de Octubre
INVESTIGADOR PRINCIPAL
Rosa AYALA DIAZ
FECHA DE APERTURA
Febrero, 2026
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
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.
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.
Patients must be affiliated to a social security system or beneficiary of the same (only for France)
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)
Subject must be 60 years of age.
Subject must have a projected life expectancy of at least 12 weeks.
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: ECOG Performance Status of 2 or 3; Cardiac history of CHF requiring treatment or Ejection Fraction 50% or chronic stable angina; DLCO 65% or FEV1 65%; Severe Renal impairement: Creatinine clearance 30 mL/min to < 45 ml/min Moderate hepatic impairment with total bilirubin > 1.5 to 3.0 × ULN Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the coordinator before study enrollment
Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status (Appendix 4): 0 to 2 for subject 75 years of age. 0 to 3 for subject 60 to 74 years of age.
Subject must have adequate renal function as demonstrated by a creatinine clearance 30 mL/min; calculated by the Cockcroft Gault formula.
Subject must have adequate liver function as demonstrated by: Aspartate aminotransferase (AST) 3.0 × ULN* alanine aminotransferase (ALT) 3.0 × ULN* bilirubin 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
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).
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.
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.
Patients must be affiliated to a social security system or beneficiary of the same (only for France)
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)
Subject must be 60 years of age.
Subject must have a projected life expectancy of at least 12 weeks.
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: ECOG Performance Status of 2 or 3; Cardiac history of CHF requiring treatment or Ejection Fraction 50% or chronic stable angina; DLCO 65% or FEV1 65%; Severe Renal impairement: Creatinine clearance 30 mL/min to < 45 ml/min Moderate hepatic impairment with total bilirubin > 1.5 to 3.0 × ULN Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the coordinator before study enrollment
Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status (Appendix 4): 0 to 2 for subject 75 years of age. 0 to 3 for subject 60 to 74 years of age.
Subject must have adequate renal function as demonstrated by a creatinine clearance 30 mL/min; calculated by the Cockcroft Gault formula.
Subject must have adequate liver function as demonstrated by: Aspartate aminotransferase (AST) 3.0 × ULN* alanine aminotransferase (ALT) 3.0 × ULN* bilirubin 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
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).
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.
CRITERIOS DE EXCLUSIÓN
Subject has received treatment with the following: - Hypomethylating agent, venetoclax and/or any chemo-therapeutic agent for Myelodysplastic syndrome (MDS). - Chimeric Antigen Receptor (CAR)-T cell therapy. - Experimental therapies for MDS or Acute Myeloid Leukemia (AML). - Current participation in another research or observational study
Subject has acute promyelocytic leukemia
Subject has known active CNS involvement with AML.
Known human immunodeficiency virus HIV
Known hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months.
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.
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.
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).
Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
Subject has a history of other malignancies prior to study entry, with the exception of: Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent and considered in remission for 3 years.
Subject has a white blood cell count > 25 × 109/L. (Hydroxyurea is permitted to meet this criterion.)
Subject has hypersensitivity to the active substances of any of the excipients
Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.
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.
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.
Subject has acute promyelocytic leukemia
Subject has known active CNS involvement with AML.
Known human immunodeficiency virus HIV
Known hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months.
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.
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.
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).
Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
Subject has a history of other malignancies prior to study entry, with the exception of: Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent and considered in remission for 3 years.
Subject has a white blood cell count > 25 × 109/L. (Hydroxyurea is permitted to meet this criterion.)
Subject has hypersensitivity to the active substances of any of the excipients
Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.
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.
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.
DESCRIPCIÓN
To demonstrate the non-inferiority of a reduced VEN exposure to 7 days of AZA every 28 days cycle from the first cycle in terms of composite complete remission rate (complete remission + complete remission with incomplete marrow recovery CR/CRi) at any time point during the first 6 cycles compared to conventional continuous 28-day exposure in treatment naïve AML patients.
PALABRAS CLAVE
acute myeloid leukemia, leucemia linfocítica crónica (llc / cll), leukemia
