Study of BEBT-908 Combined With Drugs in the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

• Status: Recruiting
• Trial end date: 2025-11-05
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, open Phase Ib clinical study to evaluate the safety,efficacy and pharmacokinetics of BEBT-908 combined with Rituximab (R) or combined with Rituximab-Gemcitabine-Oxaliplatin (R-GemOx) or combined with Rituximab-Ifosfamide-Carboplatin-Etoposide (R-ICE) in the treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: BeBetter Med Inc
• Treatments: Carboplatin; Etoposide; Gemcitabine; Ifosfamide; Oxaliplatin; Rituximab

Criteria

Inclusion Criteria:

1. The subject is willing to sign the informed consent form (ICF) after comprehensive understanding;

2. Age ≥18 years and ≤75 years, both male and female;

3. The pathology was confirmed as diffuse large B-cell lymphoma according to the 2016 World Health Organization classification definition;

4. Evaluation by Positron Emission Computed Tomography (PET-CT) or Computed Tomography (CT) or Magnetic resonance imaging (MRI) using Lugano 2014 standard, with measurable lesion injection;

5. Must have recurrent or refractory diffuse large B-cell lymphoma after at least 1 systemic therapy, and at least 1 systemic therapy included CD20 antibody;

6. Eastern Cooperative Oncology Group (ECOG) scores 0-2 points;

7. Life expectancy >12 weeks;

8. The level of organ function must meet the following requirements:

Peripheral blood:

1. Absolute neutrophil count (ANC) ≥1000/μL;

2. Hemoglobin (HGB) ≥8g/dL;

3. Platelet count (PLT) ≥100,000/μL;

Liver function:

1. Serum total bilirubin ≤1.5×ULN (for patients with Gilbert syndrome, total bilirubin <3.0×ULN and Direct bilirubin within normal range);

2. Serum creatinine <1.5×ULN;

3. ALT, AST or ALP≤2.5×ULN (≤5×ULN when liver involvement occurs).

Exclusion Criteria:

1. Known severe allergy to the investigational drug or any of its excipients;

2. Due to the possibility of genotoxicity, mutagenicity and teratogenicity of the investigational drug, the following subjects should be excluded:

1. Men and women who have not had sperm or egg preservation in vitro before the trial and plan to have another child within 5 years unless subsequent studies confirm reproductive safety;

2. Pregnant or lactating women;

3. Primary central nervous system lymphoma or lymphoma invading the central nervous system;

4. Previous chronic lymphoma transformation (such as Richter syndrome, prelymphocytic leukemia, etc.);

5. There are other active malignant tumors requiring treatment that may interfere with the study;

6. Pre-trial treatment:

1. Received any persistent or intermittent PI3K inhibitor and HDAC inhibitor prior to enrollment or received other small-molecule targeted drug therapy within 2 weeks;

2. Received BEBT-908 (not allowed to be in all cohorts) or R-ICE (not allowed to be in cohorts with BEBT-908+R-ICE) or R-GemOx (not allowed to be in cohorts with BEBT-908+R-GemOx) prior to enrollment;

3. Autologous hematopoietic stem cell transplantation within 3 months before enrollment;

4. Received radiotherapy that affected the evaluation of the efficacy of the study or local supportive radiotherapy that affected the bone marrow function of the subjects within 3 months before enrollment;

5. Received myelosuppressive chemotherapy or biotherapy within 3 weeks prior to enrollment;

6. Used Chinese medicines and proprietary Chinese medicines with anti-tumor effects within 2 weeks before enrollment;

7. Undergone major surgery other than tumor biopsy within 4 weeks prior to enrollment, or the side effects of surgery had not stabilized;

8. Any hematopoietic colony-stimulating factor (e.g., granulocyte colony-stimulating factor G-CSF, granulocyte macrophage colony-stimulating factor GM-CSF) or thrombopoietin TPO were treated within 2 weeks prior to enrollment；

9. Received prednisone >10mg daily (or another equivalent dose of glucocorticoid) within 7 days prior to enrollment;

10. Received chimeric antigen receptor T cell immunotherapy (CAR-T therapy) within 3 months before enrollment;

7. Persistent grade 2 or higher [Common Terminology Criteria for Adverse Events V5.0 standard (CTCAE V5.0 standard)] toxicity after previous treatment (chemotherapy or biotherapy), not stable at enrollment (except alopecia);

8. Active clinical severe infection of grade 2 or above (CTCAE V5.0 standard);

9. Complicated diseases:

1. diabetes mellitus with poor glycemic control (random glycemic value ≥11.1mmol/L after hypoglycemic treatment, or glycosylated hemoglobin（HbA1c）≥ 8.5%);

2. severe lung disease (CTCAE V5.0 grade III-IV);

3. Serious heart disease;

4. have significant kidney or liver dysfunction;

5. Poorly controlled active diseases such as hepatitis B or C;

6. Known human immunodeficiency virus (HIV) positive;

7. A history of mental illness, family history of mental illness, or mood disorder, as judged by the investigator or psychologist, and the researcher judged that they were not suitable for inclusion;

8. Combination of anticoagulation and antiplatelet therapy is required during the study period;

9. uncontrolled hypertension (systolic blood pressure ≥180mmHg and/or diastolic blood pressure ≥110mmHg);

10. Serious physical disease combined with the risk of major bleeding or a history of major bleeding;

10. Combined with use of drugs that cause QT interval prolongation or torsional ventricular tachycardia;

11. Receiving cytochrome P450 (CYP) 3A4 isozyme suppressant or strongly induced drug therapy during the first 4 weeks of enrollment；

12. Participated in other clinical trials and used investigational drugs within 4 weeks before enrollment;

13. Any condition that the investigator determines to be unstable or likely to compromise the subject's safety and compliance with the study;

14. Subjects deemed unsuitable for treatment with this protocol by the investigator.