BEBT-908 in MEF2D-Rearranged Relapsed/Refractory or MRD-Positive B-Cell Precursor Acute Lymphoblastic Leukemia

Korábbi kezelés

• Inadequate washout from prior therapy:
  • Chemotherapy, radiotherapy, immunotherapy, or other clearly anti-leukemia treatment within 14 days;
  • Small-molecule investigational or targeted therapy within 14 days or 5 half-lives, whichever is shorter;
  • Large-molecule therapy within 28 days or 5 half-lives, whichever is shorter;
  • CAR-T therapy or autologous transplantation within 60 days with ongoing active CRS, ICANS, or uncontrolled toxicity;
  • Allogeneic transplantation within 100 days, or active graft-versus-host disease or ongoing systemic immunosuppressive therapy.

Más betegség

• Isolated extramedullary relapse, or active extramedullary leukemia without bone marrow disease meeting one of the protocol-defined enrollment pathways.
• Failure to confirm MEF2D rearrangement during screening.
• Uncontrolled active infection, active invasive fungal infection, active tuberculosis, sepsis, or septic shock.
• Uncontrolled HBV, HCV, or HIV infection; active syphilis; or active EBV- or CMV-related organ disease.
• Uncontrolled or clinically significant cardiovascular disease, including recent myocardial infarction, unstable angina, severe heart failure, or severe arrhythmia.
• Known hypersensitivity to ifupinostat or any component of the formulation.
• Another malignancy that may interfere with assessment of efficacy or safety in this study, except for malignancies considered cured and at low risk of recurrence at the investigator's discretion.
• Psychiatric, cognitive, or compliance-related problems that prevent adequate understanding of or adherence to study requirements.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.

Laborértékek

• White blood cell count ≥25 × 10\^9/L before the first dose despite cytoreduction, or an unacceptable risk of leukostasis, tumor lysis syndrome, severe infection, severe bleeding, or other acute complications as judged by the investigator.
• Screening QTcF \>450 ms in males or \>470 ms in females; congenital long QT syndrome; clinically significant arrhythmia; or requirement for continued use of an irreplaceable medication known to prolong the QT interval.
• Inability to avoid strong CYP3A4 inducers, or requirement for long-term use of strong CYP3A4 inhibitors or QT-prolonging drugs that cannot be safely managed.

Egyéb

• Active central nervous system leukemia.
• Pregnancy or breastfeeding.

• Voluntary participation in the study and provision of written informed consent. For participants aged 14-17 years, written informed consent must be provided by a legal guardian, together with the participant's assent or confirmation as required by the ethics committee.
• Age ≥14 years and ≤75 years at the time of informed consent, regardless of sex.
• Diagnosis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) based on morphology, immunophenotyping, and clinical assessment.
• Prior clinical testing suggesting MEF2D rearrangement, with confirmation of the MEF2D rearrangement and its specific fusion partner during screening by RNA sequencing or a targeted RNA fusion panel.
• Meets either of the following baseline disease-status criteria:
  • Relapsed/refractory disease: relapse, refractory disease, or disease progression after at least one line of systemic anti-leukemia therapy, with evaluable bone marrow and ≥5% blasts/lymphoblasts at screening; or
  • Morphologic remission with MRD positivity: achievement of CR, CRh, or CRi after at least one course of standard induction or salvage therapy, with flow cytometry MRD ≥0.01% and/or MEF2D fusion transcript/ABL1 ≥0.1% at screening.
• Bone marrow morphology, flow cytometry MRD, and quantitative RT-qPCR for the MEF2D fusion transcript are all performed during screening and meet the applicable baseline stratification and enrollment requirements. Participants in MLFS are not eligible through the MRD-positive pathway.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Estimated life expectancy \>12 weeks.
• Peripheral blood white blood cell count \<25 × 10\^9/L before the first dose of ifupinostat hydrochloride; cytoreduction during screening is permitted to achieve this threshold.
• Adequate organ function:
  • ALT and AST ≤2.5 × ULN; values up to ≤5 × ULN may be permitted when abnormalities are attributable to leukemic hepatic involvement, prior therapy, or another controllable cause, at the investigator's discretion;
  • Total bilirubin ≤1.5 × ULN; ≤3 × ULN is permitted for Gilbert syndrome;
  • Creatinine clearance ≥50 mL/min;
  • Left ventricular ejection fraction (LVEF) ≥45%.
• No active central nervous system leukemia on cerebrospinal fluid examination during screening.
• Prior therapy meets the protocol-specified washout requirements, and acute non-hematologic toxicities have recovered to CTCAE Grade 0-1, baseline, or a clinically stable level. Reductions in ANC, hemoglobin, or platelet count attributable to leukemia or prior therapy are not exclusionary.
• Participants of childbearing potential agree to use effective contraception during study treatment and for the protocol-specified period after the last dose.