NCT07301138
Not yet recruiting
Phase 2
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
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Ruijin Hospital
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- MRD negativity rate
Overview
Brief Summary
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.
Detailed Description
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 Patients who fail to reach MRD negativity will be withdrawn from the study.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
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •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+);
- •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);
- •ECOG performance status score of 0-2 at screening;
- •Expected survival is more than 3 months.
- •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.
Arms & Interventions
intervention group
Experimental
- 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.
- 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.
- Vincristine Injection, dosage of administration: 1.4mg/m2 on day 4 and 11 of odd cycles, and 28 days as a cycle.
- 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.
- Methotrexate Injection, dosage of administration: 1g/m2 on day 1 of even cycles, and 28 days as a cycle.
- 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.
Intervention: BEBT-908 (Drug)
intervention group
Experimental
- 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.
- 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.
- Vincristine Injection, dosage of administration: 1.4mg/m2 on day 4 and 11 of odd cycles, and 28 days as a cycle.
- 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.
- Methotrexate Injection, dosage of administration: 1g/m2 on day 1 of even cycles, and 28 days as a cycle.
- 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.
Intervention: Cyclophosphamide (Drug)
intervention group
Experimental
- 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.
- 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.
- Vincristine Injection, dosage of administration: 1.4mg/m2 on day 4 and 11 of odd cycles, and 28 days as a cycle.
- 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.
- Methotrexate Injection, dosage of administration: 1g/m2 on day 1 of even cycles, and 28 days as a cycle.
- 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.
Intervention: Vincristine (Drug)
intervention group
Experimental
- 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.
- 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.
- Vincristine Injection, dosage of administration: 1.4mg/m2 on day 4 and 11 of odd cycles, and 28 days as a cycle.
- 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.
- Methotrexate Injection, dosage of administration: 1g/m2 on day 1 of even cycles, and 28 days as a cycle.
- 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.
Intervention: Dexamethasone (Drug)
intervention group
Experimental
- 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.
- 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.
- Vincristine Injection, dosage of administration: 1.4mg/m2 on day 4 and 11 of odd cycles, and 28 days as a cycle.
- 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.
- Methotrexate Injection, dosage of administration: 1g/m2 on day 1 of even cycles, and 28 days as a cycle.
- 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.
Intervention: Methotrexate (Drug)
intervention group
Experimental
- 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.
- 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.
- Vincristine Injection, dosage of administration: 1.4mg/m2 on day 4 and 11 of odd cycles, and 28 days as a cycle.
- 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.
- Methotrexate Injection, dosage of administration: 1g/m2 on day 1 of even cycles, and 28 days as a cycle.
- 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.
Intervention: Cytarabine (Drug)
Outcomes
Primary Outcomes
MRD negativity rate
Time Frame: At the end of Cycle 2 of BEBT-908 combined chemotherapy treatment (each cycle is 28 days)
The proportion of patients who reach MRD negative
Secondary Outcomes
- Overall survival (OS)(up to 24 months)
- Relapse-free survival (RFS)(up to 24 months)
- Progression-Free Survival (PFS)(up to 24 months)
- Incidence of adverse events(up to 24 months)
Investigators
Jin Wang
chief physician, MD, PhD
Ruijin Hospital
Study Sites (1)
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