This is a single-center, open-label, exploratory study evaluating ifupinostat hydrochloride (BEBT-908) in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with MEF2D rearrangement. The study will include patients with relapsed or refractory disease and patients who are in morphologic remission but still have measurable residual disease (MRD).
The main purpose of the study is to evaluate the preliminary anti-leukemia activity of BEBT-908 in patients with relapsed or refractory disease and its ability to reduce or eliminate residual leukemia in patients with MRD-positive disease. The study will also assess the depth and duration of response, survival outcomes, subsequent treatment such as stem cell transplantation or CAR-T therapy, and the safety and tolerability of BEBT-908.
Approximately 10 to 15 participants aged 14 to 75 years are planned to be enrolled. All participants will receive BEBT-908 by intravenous infusion at 18.5 mg/m² on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle for up to two cycles. Bone marrow morphology, flow cytometry MRD, and MEF2D fusion transcript levels will be evaluated during the study to assess treatment response.
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.
Isolated extramedullary relapse, or active extramedullary leukemia without bone marrow disease meeting one of the protocol-defined enrollment pathways.
Active central nervous system leukemia.
Failure to confirm MEF2D rearrangement during screening.
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.
Single group
Ifupinostat Hydrochloride
DrugIfupinostat 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.
Overall Response Rate in Participants With Relapsed/Refractory Disease
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
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.
Overall Survival
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
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
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.
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The First Affiliated Hospital of Soochow University
Lead sponsor
Guangzhou BeBetter Med Co., Ltd
Collaborator
