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

• Ifupinostat Hydrochloride (Drug), also known as BEBT-908: Ifupinostat hydrochloride (BEBT-908) will be administered intravenously at a dose of 18.5 mg/m² on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle for up to 2 cycles. Each dose will be administered as a constant-rate intravenous infusion over 30 ± 5 minutes.

Primary outcomes

• Overall Response Rate in Participants With Relapsed/Refractory Disease [From first dose through Cycle 2 Day 21 ± 3 days (approximately 6 weeks)]: The proportion of participants with relapsed/refractory MEF2D-rearranged BCP-ALL who achieve a best overall response of complete remission (CR), CR with partial hematologic recovery (CRh), CR with incomplete hematologic recovery (CRi), or morphologic leukemia-free state (MLFS) during the first 2 treatment cycles.
• Complete MRD Response Rate in Participants With MRD-Positive Disease [From first dose through Cycle 2 Day 21 ± 3 days]: The proportion of participants with morphologic remission but MRD-positive MEF2D-rearranged BCP-ALL who achieve a complete MRD response, defined as flow cytometry MRD <0.01% and MEF2D fusion transcript/ABL1 <0.1% at the same assessment time point, with both measurements evaluable.

Secondary outcomes

• Overall Survival [From first dose until death or last known follow-up, up to approximately 30 months]: Overall survival is defined as the time from the first dose of ifupinostat hydrochloride to death from any cause. Participants who remain alive will be censored at the date they were last known to be alive.
• Event-Free Survival [From first dose until an EFS event or last follow-up, up to approximately 30 months]: Event-free survival (EFS) will be evaluated separately by baseline disease stratum. In the relapsed/refractory stratum, events include failure to achieve CR, CRh, CRi, or MLFS after 2 cycles, disease progression, morphologic relapse after response, initiation of new anti-leukemia therapy for insufficient efficacy, or death from any cause. In the MRD-positive stratum, events include failure to achieve complete MRD response after 2 cycles, MRD progression, morphologic relapse, initiation of new anti-leukemia therapy for insufficient efficacy, or death from any cause.
• Incidence of Adverse Events and Serious Adverse Events [From first dose through 28 days after the last dose]: Incidence and severity of adverse events (AEs), serious adverse events (SAEs), Grade 3-4 AEs, and treatment-related AEs, assessed using NCI CTCAE version 5.0. Events will also be summarized by relationship to study treatment and by whether they resulted in treatment interruption, modification, or discontinuation.

Sex: All, ages: 14 Years to 75 Years

Inclusion Criteria:

1. 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.
2. Age ≥14 years and ≤75 years at the time of informed consent, regardless of sex.
3. Diagnosis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) based on morphology, immunophenotyping, and clinical assessment.
4. 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.
5. Meets either of the following baseline disease-status criteria:

   1. 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
   2. 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.
6. 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.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
8. Estimated life expectancy >12 weeks.
9. 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.
10. 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%.
11. No active central nervous system leukemia on cerebrospinal fluid examination during screening.
12. 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.
13. Participants of childbearing potential agree to use effective contraception during study treatment and for the protocol-specified period after the last dose.

Exclusion Criteria:

1. Isolated extramedullary relapse, or active extramedullary leukemia without bone marrow disease meeting one of the protocol-defined enrollment pathways.
2. Active central nervous system leukemia.
3. Failure to confirm MEF2D rearrangement during screening.
4. 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.
5. 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.
6. Uncontrolled active infection, active invasive fungal infection, active tuberculosis, sepsis, or septic shock.
7. Uncontrolled HBV, HCV, or HIV infection; active syphilis; or active EBV- or CMV-related organ disease.
8. 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.
9. Uncontrolled or clinically significant cardiovascular disease, including recent myocardial infarction, unstable angina, severe heart failure, or severe arrhythmia.
10. Pregnancy or breastfeeding.
11. Known hypersensitivity to ifupinostat or any component of the formulation.
12. 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.
13. 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.
14. Psychiatric, cognitive, or compliance-related problems that prevent adequate understanding of or adherence to study requirements.
15. Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.