Status:
UNKNOWN
Study of BEBT-908 in the Relapsed or Refractory Diffuse Large B-cell Lymphoma Subjects
Lead Sponsor:
BeBetter Med Inc
Conditions:
Relapsed or Refractory Diffuse Large B-cell Lymphoma
Eligibility:
All Genders
18-75 years
Phase:
PHASE2
Brief Summary
This is an open,single-arm,multicenter phase II clinical study to evaluate the efficacy and safety of BEBT-908 for injection in the treatment of relapsed or refractory diffuse large B-cell lymphoma. T...
Detailed Description
This is an open, single-arm, multicenter phase II clinical study to evaluate the efficacy and safety of BEBT-908 for injection in the treatment of relapsed or refractory diffuse large B-cell lymphoma....
Eligibility Criteria
Inclusion
- The subject is willing to sign the informed consent form (ICF) after a comprehensive understanding.
- Age ≥ 18 years and ≤ 75 years, male or female.
- Diffuse large B-cell lymphoma was confirmed by central pathological examination and tissue biopsy.(Note 1)
- With measurable lesions.(Note 2)
- Refractory or relapse after at least two kinds of systematic treatment. (Note 3)
- Eastern Cooperative Oncology Group (ECOG) score ≤ 2.
- Life expectancy \> 12 weeks.
- The level of organ function must meet the following requirements:
- Peripheral blood:
- Absolute neutrophil count (ANC) ≥ 1000 /μL.
- Hemoglobin (HGB) ≥ 8g/dL.
- Platelet count (PLT) ≥ 1000000 /μL.
- Liver function:
- Serum total bilirubin ≤ 1.5 × Upper limit of normal value （ULN） (for patients with Gilbert syndrome, total bilirubin \< 3.0 × ULN and direct bilirubin within the normal range).
- Serum creatinine \< 1.5 × ULN.
- Alanine aminotransferase （ALT）, aspartate aminotransferase （AST） or alkaline phosphatase （ALP ）≤ 2.5 × ULN (≤ 5 × ULN when liver involvement is involved).
- 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 node lesions is more than 15 mm under enhanced Computed Tomography （ （CT ）or Magnetic Resonance Imaging (MRI), the longest diameter of extranodal lesions is more than 10 mm, or the longest diameter of extranodal lesions is ≥ 10 mm under Positron Emission Tomography/Computed Tomography (PET/CT). Bone marrow aspiration cytology and / or biopsy may be performed when evaluating the curative effect.
- Note 3: Relapsed / refractory diffuse large B lymphoma is defined in this regimen as: 1) relapsed more than 6 months after the end of second-line treatment; 2) those who relapse within 6 months after the end of second-line treatment and those who do not reach partial response (PR) for 2 or more cycles of second-line treatment can be selected as refractory patients without the requirement of treatment cycle. 3) after sequential hematopoietic stem cell transplantation with second-line therapy, recurrence within 6 months can be included in the group. Previous treatment should include anti-CD20 monoclonal antibody and cytotoxic drug therapy; anti-CD20 monoclonal antibody consolidation therapy or induction therapy cannot be counted as a single line of treatment; previous stem cell transplantation is allowed; autologous stem cell transplantation or allogeneic stem cell transplantation alone does not count as first-line therapy, induction, consolidation, stem cell collection, pretreatment regimen and transplantation ±maintenance therapy belong to the same line of treatment.
Exclusion
- It is known to be severely allergic to research drugs or any of their excipients.
- Because the research drugs may have genotoxicity, mutagenicity and teratogenicity, the following subjects should be excluded:
- Men and women who plan to reproduce within 5 years without in vitro preservation of sperm or eggs before the trial. Unless follow-up studies confirm reproductive safety.
- pregnant or lactating women.
- Primary central nervous system lymphoma or lymphoma invading the central nervous system.
- Previous transformation of chronic lymphoma (such as Richter syndrome, pre-lymphocytic leukemia, etc.).
- There are other active malignant tumors that may interfere with this study.
- Pre-trial treatment:
- Have received any persistent or intermittent treatment such as Phosphoinositide 3-kinase (PI3K) inhibitors, Mammalian Target of Rapamycin (mTOR) inhibitors or Histone Deacetylase (HDAC) inhibitors or other small molecule targeted drugs within 2 weeks before entering the group.
- Autologous hematopoietic stem cell transplantation within 3 months before enrollment.
- Received radiotherapy that affected the efficacy evaluation of this study or local supportive radiotherapy that affected the bone marrow function of the subjects within 3 months before enrollment.
- Bone marrow inhibitory chemotherapy or biotherapy was performed within 3 weeks before enrollment.
- Major surgery other than tumor biopsy was performed within 4 weeks before enrollment, or the side effects of the operation were not stable.
- Received any hematopoietic colony-stimulating factor therapy (such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF)) or thrombopoietin （TPO） within 2 weeks before enrollment. (Note 1)
- received prednisone daily \> 10mg (or other dose-effective corticosteroids) within 7 days before enrollment. (Note 2)
- Chimeric antigen receptor T cell immunotherapy (CAR-T therapy) was performed within 3 months before enrollment.
- After the previous treatment (chemotherapy or biotherapy), there were persistent toxicity of grade 2 or above (Common Terminology Criteria for Adverse Events V5.0 （CTCAE V5.0 ）), which was not stable at the time of admission (except hair loss).
- There are severe clinical infections in active stage with grade 2 or above (CTCAE V5.0).
- Concomitant disease:
- Diabetes with poor blood glucose control (random blood glucose ≥ 11.1mmol/L or Hemoglobin A1C (HbA1c ）≥ 8.5% after hypoglycemic treatment).
- Severe lung disease (CTCAE V5.0, III-IV).
- Severe heart disease. (Note 3)
- With significant renal or liver dysfunction.
- Poorly controlled active hepatitis B or C diseases;(Note 4)
- known to be HIV positive.
- A history of mental illness, family history of mental illness or emotional disorder is determined by a researcher or psychiatrist. (Note 5)
- Combined use of drugs that cause prolonged QT interval or twisted ventricular tachycardia.
- The patients were treated with cytochrome P450 (CYP) 3A4 isozyme inhibitors or strong induction drugs within 4 weeks before enrollment. (Note 6)
- Participated in other clinical trials and used research drugs within 4 weeks before joining the group.
- The researchers judged any unstable or likely to endanger the safety of subjects and their compliance with the study.
- The researchers believe that it is not suitable for subjects who are treated with this regimen.
- Note 1: Subjects who began to receive erythropoietin or diplotene within 2 weeks before enrollment can be enrolled in the group.
- Note 2: If used to treat diseases other than lymphoma, such as rheumatoid arthritis, rheumatic polymyalgia, adrenocortical dysfunction or asthma, subjects can receive a maximum daily dose of 10mg with a stable dose of prednisone (or other equivalent glucocorticoid).
- Note 3: Including any of the following: left ventricular ejection fraction (LVEF) \< 50% found by cardiac radionuclide scanning (Multigated Radionuclide Angiography （MUGA）) or echocardiography (ECHO) corrected QT value (QTcF interval) male \> 450ms, female \> 470ms (QTcF formula); unstable angina pectoris; symptomatic pericarditis; abnormal recording of the left ventricular wall in areas with persistent elevated myocardial enzymes or persistent LVEF function measurements in the past 6 months of myocardial infarction.
- History of congestive heart failure (New York College of Cardiology III-IV Appendix 3), cardiomyopathy record.
- Note 4: The following active infections with clinical significance, including hepatitis B (HBV) and hepatitis C (HCV). Active hepatitis B is defined as hepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg) positive, and HBV DNA ≥ 2000 IU/ml (equivalent to 10\^4 copies / ml), (hepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg) positive, HBV DNA \< 2000 IU/ml, according to infectious disease control requirements, subjects should continue to take entecavir until one year after the end of the study). Active hepatitis C is defined as: HCV RNA is higher than the upper limit of detection.
- Note 5: including medical records with history of depressive episodes, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, suicidal attempts or suicidal ideations, or thoughts of "being at immediate risk of harming others", anxiety level 3 or above, etc.
- Note 6: moderate or weak CYP3A inhibitors are allowed in combination; a list of common CYP3A4 inhibitors or inducers is shown in Appendix 5 of the study scheme.
Key Trial Info
Start Date :
June 12 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 25 2023
Estimated Enrollment :
128 Patients enrolled
Trial Details
Trial ID
NCT06074107
Start Date
June 12 2020
End Date
December 25 2023
Last Update
October 11 2023
Active Locations (1)
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1
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, China, 100021