BEBT-908 Plus Chemotherapy Treatment for CR MRD-Positive MEF2D-Rearranged and Pre-B Acute Lymphoblastic Leukemia Patients

MEF2D-rearranged and pre-B acute lymphoblastic leukemia patients achieving CR after chemotherapy and have MRD+ will be given BEBT-908 (12.3 mg/m2) combined with Mini-Hyper-CVD and Mini-MTX/Ara-C chemotherapy for two cycles.

After two cycles, If MRD negativity is achieved and the patient is eligible for transplantation, hematopoietic stem cell transplantation will be performed; if MRD negativity is achieved but the patient is not suitable for transplantation, an additional six courses of BEBT-908-based combination chemotherapy will be given. Patients who fail to reach MRD negativity will be withdrawn from the study.

A total of 23 patients will be enrolled

Inclusion criteria

• The subject voluntarily agrees to participate in this trial and signs the informed consent form, and is able to understand and comply with all study requirements;
• Age between ≥18 and ≤75 years at screening, with no gender restrictions;
• Meets the diagnostic criteria for BCP-ALL (according to the 2022 WHO classification) and fulfills any one of the following conditions:

• Positive for MEF2D rearrangement 2) Philadelphia chromosome negative and consistent with a Pre-B immunophenotype (according to the EGIL 1995 immunophenotyping criteria, cytoplasmic IgM+); 4. Diagnosed with BCP-ALL in complete remission but with positive minimal residual disease (MRD), defined as: achieving hematologic complete remission (CR) after treatment (bone marrow blast count <5% by morphology) but with positive MRD (MRD ≥10-⁴, as detected by flow cytometry and/or PCR); 5. ECOG performance status score of 0-2 at screening; 6. Expected survival is more than 3 months. 7. Satisfactory organ function, meeting the following criteria:

• Serum creatinine ≤1.5 times the upper limit of normal（ULN）；
• Left ventricular ejection fraction (LVEF) >50%; 3）Total bilirubin ≤2 times ULN；Alanine aminotransferase (ALT) ≤3 times ULN; Aspartate aminotransferase (AST) ≤3 times ULN

Exclusion criteria

• Known allergy to the study drug or its excipients.
• Presence of severe and/or uncontrolled infection.
• Severe cardiac disease, including: heart failure classified as New York Heart Association (NYHA) functional class III or IV; history of acute myocardial infarction within 6 months prior to screening; uncontrolled arrhythmias or electrophysiological abnormalities such as sick sinus syndrome, third degree atrioventricular block, QTc > 480 ms, ventricular tachycardia, persistent atrial fibrillation with rapid ventricular response, etc.; or severe structural cardiac abnormalities on echocardiography or left ventricular ejection fraction (LVEF) < 50 %.
• Primary central nervous system diseases, including cerebrovascular accident, intracranial infection, etc., within six months before screening.
• Severe primary pulmonary diseases, including significant impairment of pulmonary ventilation/diffusion function, respiratory failure, etc.
• Severe hepatic impairment: total bilirubin (TB), gamma glutamyl transferase (γGT), ALT, or AST > 3 times ULN at baseline or after hepatoprotective therapy; or conditions such as severe hepatitis, cirrhosis, etc.
• Severe renal impairment: serum creatinine > 1.5 × ULN; or uncorrected acute kidney injury.
• Acute or chronic pancreatitis, with serum amylase > 3 × ULN.
• Pregnancy or lactation.
• History of other prior malignancies that may affect protocol compliance or interpretation of study results.
• Diagnosed major psychiatric disorder or predisposition to psychiatric illness that would significantly impair the ability to participate in the clinical study.
• Any other condition deemed by the investigator as unsuitable for study enrollment.