Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Conditions
Interventions
Combination group 1:Intravenous infusion of BEBT-908, rituximab, gemcitabine and oxaliplatin
Combination group 2:Intravenous infusion of BEBT-908, rituximab, ifosfamide , carboplatin and etoposide
Combination group 3:Intravenous infusion of BEBT-908 and rituximab
alternative cohort 1:monotherapy group :Intravenous infusion of BEBT-908
alternative cohort 2:Combination group:Intravenous infusion of BEBT-908, rituximab, gemcitabine and oxaliplatin
Sponsors
Cancer Hospital Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion 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 (Note 1); 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 (Note 2) ; 5. Must have relapse or refractory diffuse large B-cell lymphoma after at least 1 systemic therapy(Note 3), and at least 1 systemic therapy included CD20 antibody; 6. Eastern Cooperative Oncology Group (ECOG) score is 0-2 points; 7. Life expectancy >12 weeks; 8. The level of organ function must meet the following requirements: Peripheral blood: a. Absolute neutrophil count (ANC) =1000/µL; b. Hemoglobin (HGB) =8g/dL; c. Platelet count (PLT) =100,000/µL; Liver function: a. Serum total bilirubin =1.5×ULN (for patients with Gilbert syndrome, total bilirubin <3.0×ULN and direct bilirubin within normal range); b. Serum creatinine <1.5×ULN; c. ALT, AST or ALP=2.5×ULN (=5×ULN when liver involvement occurs). Note 1:Patients with recurrence for more than one year need to undergo another tissue biopsy to confirm the pathological diagnosis. Note 2: The criteria for measurable lesions are as follows: the longest diameter of lymph nodes is more than 15 mm under enhanced CT or MRI, the longest diameter of extranodal lesions is more than 10 mm;,or the longest diameter of extranodal lesions is = 10 mm and the maximum vertical diameter = 10 mm under PET/CT; can be evaluated by bone marrow aspiration cytology and / or biopsy. Note 3: Salvage chemo-immunotherapy after stem cell transplantation will be regarded as first-line systemic therapy; maintenance therapy will not be included in a separate systemic treatment line; local DLBCL radiotherapy for curing purposes will not be included in first-line systemic therapy; patients with 4 treatment cycles of first-line treatment that do not reach PR can be included in the study; patients with second-line or more treatment cycles that do not reach PR can be included in the study. Patients with primary refractory DLBCL are defined as having no remission during first-line treatment and relapse within 6 months after the end of treatment. Patients with relapse within 12 months after stem cell transplantation were allowed to enter the group.
Exclusion criteria
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: a)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; b) 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: a) Received any persistent or intermittent PI3K inhibitor and HDAC inhibitor prior to enrollment or received other small-molecule targeted drug therapy within 2 weeks; b) 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; c) Autologous hematopoietic stem cell transplantation within 3 months before enrollment; d) 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; e) Received myelosuppressive chemotherapy or biotherapy within 3 weeks prior to enrollment; f) Used Chinese medicines and proprietary Chinese medicines with anti-tumor effects within 2 weeks before enrollment; g) Undergone major surgery other than tumor biopsy within 4 weeks prior to enrollment, or the side effects of surgery had not stabilized; h) 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(Note 1); i) Received prednisone>10mg daily (or another equivalent dose of glucocorticoid) within 7 days prior to enrollment(Note 2); j) 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: a) diabetes mellitus with poor glycemic control (random glycemic value =11.1mmol/L after hypoglycemic treatment, or glycosylated hemoglobin(HbA1c)= 8.5%); b) severe lung disease (CTCAE V5.0 grade III-IV); c) Serious heart disease(Note 3); d) have significant kidney or liver dysfunction; e) Poorly controlled active diseases such as hepatitis B or C; f) Known human immunodeficiency virus (HIV) positive(Note 4); g) A history of mental illness, family history of mental illness, or mood disorder, as judged by the investigator or psychologist(Note 5), and the researcher judged that they were not suitable for inclusion; h) Combination of anticoagulation and antiplatelet therapy is required during the study period; i) uncontrolled hypertension (systolic blood pressure =180mmHg and/or diastolic blood pressure =110mmHg); j) Serious physical disease combined with the risk of major bleeding or a history of major bleeding; 10. C
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate;Adverse event; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate after completion of treatment;Progression-free survival;Overall Survival;Clinical benefit rate;Duration of Response;Disease Control Rate;Treatment response time;Pharmacokinetics; | — |
Countries
China
Contacts
Public ContactChanggeng Qian
BeBetter Med Inc.
Outcome results
None listed