AML patients who do not achieve complete remission after a single course of induction chemotherapy
Conditions
Interventions
Eligible patients will be randomized to receive either venetoclax plus azacitidine or conventional intensive chemotherapy for remission induction and consolidation therapy.
Sponsors
Kiyoi Hitoshi
Kiyoi Hitoshi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Patients diagnosed with acute myeloid leukemia (AML) according to the WHO classification (2016), aged 16 years or older and under 65 years at the time of consent. (2) Patients who failed to achieve complete remission (defined as >=5% blasts in bone marrow) after one course of standard induction therapy, which includes: Standard adult AML induction therapy combining an anthracycline and cytarabine (e.g., per JALSG AML201 protocol), CPX-351, or Standard pediatric AML induction therapy based on the JCCG AML protocol (including intrathecal therapy). (3) Patients expected to be eligible for allogeneic hematopoietic stem cell transplantation after re-induction therapy in this study. (4) Patients with an ECOG Performance Status of 0, 1, or 2. (5) Patients with adequate liver, renal, pulmonary, and cardiac function, defined as: a. Total serum bilirubin = 60 Torr or SpO2 >= 90% on room air before treatment d. No significant cardiac dysfunction, defined as the need for a cardiac pacemaker, uncontrolled ventricular or atrial tachyarrhythmias despite medication, or a left ventricular ejection fraction (LVEF) < 50% on echocardiography. (6) Written informed consent has been obtained from the patient. For patients under 18 years of age, consent must also be obtained from a legally authorized representative. (7) In the case of male or female patients of childbearing potential, those who agree to use contraception during the study and for a certain period after the last administration of the investigational drug, in accordance with the package insert of each drug.
Exclusion criteria
Exclusion criteria: - Patients diagnosed with acute promyelocytic leukemia (APL) - Patients diagnosed with core-binding factor AML (CBF-AML) in whom RUNX1::RUNX1T1 or CBFB::MYH11 fusion genes were detected at initial diagnosis - Patients with FLT3-ITD-positive AML, as identified by FLT3 mutation testing at initial diagnosis - Patients with BCR::ABL1-positive leukemia (i.e., chronic myeloid leukemia in blast crisis) - Patients with hematologic disorders associated with congenital syndromes - Patients with active malignancies other than AML or myelodysplastic syndromes (MDS); however, patients with a disease-free interval of >= 2 years prior to study enrollment may be eligible - Patients with clinically active central nervous system (CNS) leukemia - Patients with a history of venetoclax use - Patients with unstable angina or a history of myocardial infarction within the past 6 months - Patients with uncontrolled active infections - Patients with active hepatitis B, hepatitis C, or active hepatitis of other etiologies (patients with inactive carrier status may be included) - Patients who are HIV-positive - Patients with liver cirrhosis - Patients with a history of renal failure - Patients with a known history of hypersensitivity to any component of the investigational product - Patients with psychiatric disorders that interfere with daily functioning, require supervision or physical restraint, or preclude continued inpatient treatment despite psychiatric care or medication - Pregnant women or women who may be pregnant - Any other condition that, in the opinion of the principal investigator or sub-investigators, makes the patient unsuitable for participation in this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy after one course of study treatment, defined as the rate of composite complete remission (CRc) plus morphologic leukemia-free state (MLFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| - Complete remission rate and composite complete remission (CRc) rate based on best treatment response - Overall survival (OS) rate at 3 years - Disease-free survival (DFS) rate at 3 years (both with and without censoring at allogeneic hematopoietic stem cell transplantation) - Pre-transplant complete remission rate, CRc rate, and MRD negativity rate - Proportion of patients who undergo allogeneic hematopoietic stem cell transplantation - Cumulative incidence of non-relapse mortality and relapse among transplant recipients - Incidence of adverse events | — |
Contacts
Public ContactYuichi Ishikawa
Nagoya University Hospital
Outcome results
None listed