Phase Ⅲ Clinical Trial Comparing BEBT-908 Combined With Rituximab (R) to Standard of Care for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Overview
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- BeBetter Med Inc
- Enrollment
- 416
- Locations
- 1
- Primary Endpoint
- Overall Survival (OS)
Overview
Brief Summary
This is a multicenter, randomized, controlled, open-label Phase III clinical trial, aimed at evaluating the efficacy and safety of BEBT-908 combined with rituximab (R) compared to investigator-selected standard chemotherapy regimens [Standard of Care (SOC)] [i.e., rituximab-gemcitabine-oxaliplatin (R-GemOx) or rituximab-ifosfamide-carboplatin-etoposide (R-ICE)] for the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL).
Detailed Description
The study will recruit 416 subjects, who will be randomly assigned in a 1:1 ratio to either the experimental group (BEBT-908 combined with R) or the control group [investigator-selected standard chemotherapy regimen (R-GemOx or R-ICE)]. Approximately 208 subjects will be enrolled in the experimental group, and approximately 208 in the control group. The treatment cycle is 21 days, with a total of 8 treatment cycles. The experimental group will receive BEBT-908 + R treatment from cycles 1 to 8; participants who do not appear progressive disease (PD) after cycle 8 may continue to receive BEBT-908 and/or R treatment, entering a maintenance phase of up to 24 months. The control group will receive the investigator-selected SOC (i.e., R-GemOx or R-ICE) treatment from cycles 1 to 8, and will not receive further study medication after cycle 8.
Each subject's study process includes three phases: screening, treatment, and post-treatment follow-up. The screening phase can last up to 21 days. During the treatment phase, tumor assessments will be conducted every 6 weeks (±7 days) within the first 8 treatment cycles, and every 9 weeks (±7 days) after cycle 8.After the end of treatment, safety follow-up will be conducted on day 28 (+7 days) after the last dose, efficacy follow-up will be conducted every 9 weeks (±7 days), and survival follow-up will be conducted every 3 months (±2 weeks).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- 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 has been fully informed and is willing to sign the Informed Consent Form (ICF).
- •Age is ≥18 years and ≤75 years, both men and women are eligible.
- •Pathologically diagnosed as diffuse large B-cell lymphoma according to the 2022 World Health Organization classification, confirmed by central pathology review (Patients who relapse after more than one year need to undergo tissue biopsy again to confirm the pathological diagnosis.).
- •Measurable lesions \[The criteria for measurable lesions are: the longest diameter of lymph node lesions measured by enhanced Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) is greater than 15 mm, and the longest diameter of extranodal lesions is greater than 10 mm.\] assessed by Positron Emission Tomography/Computed Tomography (PET-CT) and Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) according to the Lugano 2014 criteria .
- •Must have relapsed or refractory diffuse large B-cell lymphoma after at least one systemic therapy \[Salvage chemotherapy and immunotherapy after stem cell transplantation will be considered as first-line systemic treatment; maintenance therapy will not be counted as a separate line of systemic treatment; local radiotherapy for diffuse large B-cell lymphoma (DLBCL) aimed at cure will not be counted as first-line systemic treatment; patients who do not achieve PR after four cycles of first-line treatment are eligible for the study; patients who do not achieve PR after two cycles of second-line or higher treatment are eligible for the study. Primary refractory DLBCL patients are defined as those who have no response during first-line treatment or relapse within six months after the end of treatment, and they will be allowed to participate in the study. Patients who relapse within 12 months after stem cell transplantation are also eligible for inclusion. Refractory DLBCL patients are those who do not achieve response after adequate front-line treatment (at least four cycles of first-line chemotherapy, or at least two cycles of subsequent treatment), or who progress during previous first-line treatment, or who progress within six months (less than six months) after achieving response to previous adequate front-line treatment, or who relapse within 12 months after achieving response to stem cell transplantation. Relapsed DLBCL patients are those who relapse six months or more after achieving response to previous adequate front-line treatment, or who relapse 12 months or more after achieving response to stem cell transplantation.\], and at least one systemic therapy must include CD20 antibody.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-
- •Expected survival \>12 weeks.
- •Organ function levels must meet the following requirements:
- •Peripheral blood:
- •Absolute neutrophil count (ANC) ≥1.0×10\^9/L;
Exclusion Criteria
- •Known severe allergy to the study drug or any of its excipients;
- •Due to the potential genotoxicity, mutagenicity, and teratogenicity of the study drug, the following subjects should be excluded:
- •Men and women who have not undergone in vitro preservation of sperm or oocytes and plan to have children within 5 years, unless subsequent studies confirm reproductive safety;
- •Pregnant or breastfeeding women;
- •Primary central nervous system lymphoma;
- •DLBCL with active central nervous system brain metastases or meningeal involvement at the time of screening;
- •Other active malignant tumors that require treatment and may interfere with the study.
- •Treatment history before the trial:
- •Received other small molecule targeted drug therapy within 2 weeks before enrollment;
- •Previously received BEBT-908 or R-ICE and R-GemOx therapy before enrollment;
Arms & Interventions
Experimental Group (BEBT-908 Combined With R)
Ifupinostat Hydrochloride for Injection,18.5mg/m^2 each time,is administered on days 1, 3, 5, 8, 10, and 12 of each cycle during cycles 1 to 8,with a 21-day cycle duration. After cycle 8, participants without PD enter a maintenance treatment phase that can last up to 24 months: Medication is administered on days 1, 3, 5, 8, 10, and 12 of each cycle, with a 21-day cycle duration, or as assessed by the investigator, medication is administered on days 1, 3, 5, 8, 10, and 12 of each cycle, with a 42-day cycle duration.
Rituximab Injection,375 mg/m^2 each time,is administered on day 1 of each cycle during cycles 1 to 8. After cycle 8, medication is administered on day 1 of every third cycle, with a 21-day cycle duration.
Intervention: Ifupinostat Hydrochloride for Injection (Drug)
Experimental Group (BEBT-908 Combined With R)
Ifupinostat Hydrochloride for Injection,18.5mg/m^2 each time,is administered on days 1, 3, 5, 8, 10, and 12 of each cycle during cycles 1 to 8,with a 21-day cycle duration. After cycle 8, participants without PD enter a maintenance treatment phase that can last up to 24 months: Medication is administered on days 1, 3, 5, 8, 10, and 12 of each cycle, with a 21-day cycle duration, or as assessed by the investigator, medication is administered on days 1, 3, 5, 8, 10, and 12 of each cycle, with a 42-day cycle duration.
Rituximab Injection,375 mg/m^2 each time,is administered on day 1 of each cycle during cycles 1 to 8. After cycle 8, medication is administered on day 1 of every third cycle, with a 21-day cycle duration.
Intervention: Rituximab Injection (Drug)
Control Group (R-GemOx or R-ICE)
Rituximab Injection,375mg/m^2 each time,is administered on day 1 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Gemcitabine Hydrochloride for Injection,1g/m^2 each time,is administered on day 2 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Oxaliplatin Injection,100mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Etoposide Injection,100mg/m^2 each time,is administered on days 1, 2, and 3 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Ifosfamide for Injection,5000mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Carboplatin Injection, with a single dose ≤800 mg [calculated based on area under the curve(AUC)=5],is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Intervention: Rituximab Injection (Drug)
Control Group (R-GemOx or R-ICE)
Rituximab Injection,375mg/m^2 each time,is administered on day 1 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Gemcitabine Hydrochloride for Injection,1g/m^2 each time,is administered on day 2 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Oxaliplatin Injection,100mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Etoposide Injection,100mg/m^2 each time,is administered on days 1, 2, and 3 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Ifosfamide for Injection,5000mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Carboplatin Injection, with a single dose ≤800 mg [calculated based on area under the curve(AUC)=5],is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Intervention: Gemcitabine Hydrochloride for Injection (Drug)
Control Group (R-GemOx or R-ICE)
Rituximab Injection,375mg/m^2 each time,is administered on day 1 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Gemcitabine Hydrochloride for Injection,1g/m^2 each time,is administered on day 2 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Oxaliplatin Injection,100mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Etoposide Injection,100mg/m^2 each time,is administered on days 1, 2, and 3 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Ifosfamide for Injection,5000mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Carboplatin Injection, with a single dose ≤800 mg [calculated based on area under the curve(AUC)=5],is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Intervention: Oxaliplatin Injection (Drug)
Control Group (R-GemOx or R-ICE)
Rituximab Injection,375mg/m^2 each time,is administered on day 1 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Gemcitabine Hydrochloride for Injection,1g/m^2 each time,is administered on day 2 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Oxaliplatin Injection,100mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Etoposide Injection,100mg/m^2 each time,is administered on days 1, 2, and 3 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Ifosfamide for Injection,5000mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Carboplatin Injection, with a single dose ≤800 mg [calculated based on area under the curve(AUC)=5],is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Intervention: Etoposide Injection (Drug)
Control Group (R-GemOx or R-ICE)
Rituximab Injection,375mg/m^2 each time,is administered on day 1 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Gemcitabine Hydrochloride for Injection,1g/m^2 each time,is administered on day 2 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Oxaliplatin Injection,100mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Etoposide Injection,100mg/m^2 each time,is administered on days 1, 2, and 3 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Ifosfamide for Injection,5000mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Carboplatin Injection, with a single dose ≤800 mg [calculated based on area under the curve(AUC)=5],is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Intervention: Ifosfamide for Injection (Drug)
Control Group (R-GemOx or R-ICE)
Rituximab Injection,375mg/m^2 each time,is administered on day 1 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Gemcitabine Hydrochloride for Injection,1g/m^2 each time,is administered on day 2 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles.
Oxaliplatin Injection,100mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Etoposide Injection,100mg/m^2 each time,is administered on days 1, 2, and 3 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Ifosfamide for Injection,5000mg/m^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Carboplatin Injection, with a single dose ≤800 mg [calculated based on area under the curve(AUC)=5],is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.
Intervention: Carboplatin Injection (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Up to 48 months
Defined as the time from the date of randomization to death due to any cause.
Secondary Outcomes
- Progression-Free Survival (PFS)(Up to 48 months)
- Overall Response Rate (ORR)(Up to 48 months)
- Overall Response Rate After Completion of Treatment (ORR-EoT)(Up to 8 treatment cycles (Each cycle is 21 days.))
- Clinical Benefit Rate (CBR)(Up to 48 months)
- Duration of Response (DoR)(Up to 48 months)
- Occurrence of Adverse Events (AEs)(Up to 48 months)