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

Официальное название

A Prospective Study of BEBT-908 in Combination With Chemotherapy for Patients With MEF2D-Rearranged and Pre-B Acute Lymphoblastic Leukemia in Complete Remission With Minimal Residual Disease Positivity

Обзор

This investigator-initiated, prospective, single-arm, multicenter clinical trial aims to evaluate the efficacy and safety of BEBT-908 (a HDAC/PI3Kα inhibitor provided by BeBetter Med Inc ,Guangzhou, China) combined with chemotherapy in patients with MEF2D-rearranged and pre-B acute lymphoblastic leukemia who are in complete remission (CR) but remain minimal residual disease (MRD) positive.

Подробное описание

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 Patients who fail to reach MRD negativity will be withdrawn from the study.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

Вмешательства

• Препарат BEBT-908
  BEBT-908 for Injection, dosage of administration: 12.3mg/m2，frequency and duration of administration: on the 1st,3rd,5th,8th,10th and 12th days of each cycle, and 28 days as a cycle.
• Препарат Cyclophosphamide
  Cyclophosphamide Injection, dosage of administration: 150 mg/m2 every 12 hours on days 1 to 3 of odd cycles, and 28 days as a cycle.
• Препарат Vincristine
  Vincristine Injection, dosage of administration: 1.4mg/m2 on day 4 and 11 of odd cycles, and 28 days as a cycle.
• Препарат Dexamethasone
  Dexamethasone Injection, dosage of administration: 20 mg per day on days 1 to 4 and 11 to 14 of odd cycles, and 28 days as a cycle.
• Препарат Methotrexate
  Methotrexate Injection, dosage of administration: 1g/m2 on day 1 of even cycles, and 28 days as a cycle.
• Препарат Cytarabine
  Cytarabine Injection, dosage of administration: 0.5 g/m2 given every 12 hours on day 2 and 3 of even cycles, and 28 days as a cycle.

Первичные конечные точки

• MRD negativity rate [Срок оценки: At the end of Cycle 2 of BEBT-908 combined chemotherapy treatment (each cycle is 28 days)]

Вторичные конечные точки (4)

• Overall survival (OS) [Срок оценки: up to 24 months]
• Relapse-free survival (RFS) [Срок оценки: up to 24 months]
• Progression-Free Survival (PFS) [Срок оценки: up to 24 months]
• Incidence of adverse events [Срок оценки: up to 24 months]

Критерии участия

Критерии включения

• 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:

1\) 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Шанхай

Идентификаторы

NCT: NCT07301138 · RJ-ALL 2025-B04

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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