A Phase 3 Randomized, Double-blind, Placebo-controlled, Study of Bleximenib, Venetoclax and Azacitidine for the Treatment of Participants with Newly Diagnosed Acute Myeloid Leukemia Harboring KMT2ARearrangements or NPM1Mutations who are Ineligible for Intensive Chemotherapy
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase III
PATOLOGÍA
Coagulopatías hemorrágicas, Leucemia linfática crónica y otros SLPC, Leucemia mieloide aguda, Linfoma, Leucemia
CENTRO INVESTIGADOR
H.U. Quirónsalud Madrid
INVESTIGADOR PRINCIPAL
Virginia Pradillo Fernandez
CENTRO INVESTIGADOR
H.U. 12 de Octubre
INVESTIGADOR PRINCIPAL
Maria Belen Calbacho Robles
CENTRO INVESTIGADOR
H.U. Ramón y Cajal
INVESTIGADOR PRINCIPAL
Pilar Herrera Puente
FECHA DE APERTURA
Julio, 2025
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
1. Be 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater) at the time of informed consent.
2. Previously untreated KMT2Ar or NPM1m AML with 10% blasts per 2022 ICC criteria. -Participants with KMT2A partial tandem duplications or amplifications are NOT eligible. - Emergency leukapheresis and/or cytoreductive therapy with hydroxyurea and/or to a total of 2 g/m2 cytarabine (cytarabine may be administered over a maximum of 5 days, not to exceed 3 doses) is permitted prior to first dose of study treatment. Note: cytoreductive therapy with cytarabine should not be given until after the screening bone marrow assessment. Leukapheresis and cytarabine must be discontinued 1 day prior to first dose of study treatment.
3. Ineligible for intensive chemotherapy based on the following criteria: 75 years of age and ineligible per physicians discretion, with ECOG performance status of 0-2 18 to <75 years of age with 1 of the following comorbidities: ECOG performance status of 2 Severe cardiac disorder (eg, congestive heart failure requiring treatment or chronic stable angina) Severe pulmonary disorder (eg, DLCO 65% or FEV1 65%) Renal impairment defined as eGFR (MDRD formula) Comorbidity that, in the investigators opinion, makes the participant unsuitable for intensive chemotherapy, which must be documented before enrollment. Ineligibility for intensive chemotherapy should be explicitly approved by a multidisciplinary team in countries in which this process is standard of care
4. Adequate renal and hepatic functions prior to randomization: -AST and ALT <3 × ULN; for participants with leukemic organ involvement (documented by biopsy or imaging) AST and ALT <5 × ULN is permitted. -Total bilirubin 3× ULN, unless of non-hepatic origin. If bilirubin rise is due to congenital nonhemolytic hyperbilirubinemia such as Gilberts syndrome (in which case conjugated bilirubin needs to be within a clinically acceptable range and total bilirubin 3 × ULN). -eGFR (MDRD formula)
5. WBC count < 25 X 10^9/ L
2. Previously untreated KMT2Ar or NPM1m AML with 10% blasts per 2022 ICC criteria. -Participants with KMT2A partial tandem duplications or amplifications are NOT eligible. - Emergency leukapheresis and/or cytoreductive therapy with hydroxyurea and/or to a total of 2 g/m2 cytarabine (cytarabine may be administered over a maximum of 5 days, not to exceed 3 doses) is permitted prior to first dose of study treatment. Note: cytoreductive therapy with cytarabine should not be given until after the screening bone marrow assessment. Leukapheresis and cytarabine must be discontinued 1 day prior to first dose of study treatment.
3. Ineligible for intensive chemotherapy based on the following criteria: 75 years of age and ineligible per physicians discretion, with ECOG performance status of 0-2 18 to <75 years of age with 1 of the following comorbidities: ECOG performance status of 2 Severe cardiac disorder (eg, congestive heart failure requiring treatment or chronic stable angina) Severe pulmonary disorder (eg, DLCO 65% or FEV1 65%) Renal impairment defined as eGFR (MDRD formula) Comorbidity that, in the investigators opinion, makes the participant unsuitable for intensive chemotherapy, which must be documented before enrollment. Ineligibility for intensive chemotherapy should be explicitly approved by a multidisciplinary team in countries in which this process is standard of care
4. Adequate renal and hepatic functions prior to randomization: -AST and ALT <3 × ULN; for participants with leukemic organ involvement (documented by biopsy or imaging) AST and ALT <5 × ULN is permitted. -Total bilirubin 3× ULN, unless of non-hepatic origin. If bilirubin rise is due to congenital nonhemolytic hyperbilirubinemia such as Gilberts syndrome (in which case conjugated bilirubin needs to be within a clinically acceptable range and total bilirubin 3 × ULN). -eGFR (MDRD formula)
5. WBC count < 25 X 10^9/ L
CRITERIOS DE EXCLUSIÓN
1. Known active leukemic involvement of the CNS
2. History of myelofibrosis
3. Cardiac disease: a. Any of the following within 6 months of randomization: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (NYHA Class III or IV uncontrolled or symptomatic arrhythmias, stroke, or transient ischemic attack. b. QTcF 470 msec. Participants with a family history of Long QT syndrome are excluded. For participants with documented wide QRS interval (eg, due to a bundle branch block), alternate methods of calculating a corrected QT interval may be appropriate for eligibility determination if recommended by a consulting cardiologist and approved by the sponsor, provided there is no evidence or history of a repolarization abnormality.
4. Chronic respiratory disease requiring supplemental oxygen
5. Active infection that is uncontrolled prior to first dose of study treatment and may interfere with the study objectives or expose the patient to undue risk by participating in the trial; an infection controlled with systemic therapy is allowed.
2. History of myelofibrosis
3. Cardiac disease: a. Any of the following within 6 months of randomization: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (NYHA Class III or IV uncontrolled or symptomatic arrhythmias, stroke, or transient ischemic attack. b. QTcF 470 msec. Participants with a family history of Long QT syndrome are excluded. For participants with documented wide QRS interval (eg, due to a bundle branch block), alternate methods of calculating a corrected QT interval may be appropriate for eligibility determination if recommended by a consulting cardiologist and approved by the sponsor, provided there is no evidence or history of a repolarization abnormality.
4. Chronic respiratory disease requiring supplemental oxygen
5. Active infection that is uncontrolled prior to first dose of study treatment and may interfere with the study objectives or expose the patient to undue risk by participating in the trial; an infection controlled with systemic therapy is allowed.
DESCRIPCIÓN
To compare the efficacy of bleximenib and VEN+AZA vs VEN+AZA alone
PALABRAS CLAVE
acute myeloid leukemia, factor xi, leucemia linfocítica crónica (llc / cll), leukemia, npm1, ph + acute lymphoblastic leukemia
