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
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).
• 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 0-2.
• Expected survival \>12 weeks.
• Organ function levels must meet the following requirements:
⁃ Peripheral blood:
• Absolute neutrophil count (ANC) ≥1.0×10\^9/L;
• Hemoglobin (HGB) ≥80g/L;
• Platelet count (PLT) ≥100×10\^9/L;
⁃ Liver and kidney function:
• Serum total bilirubin ≤1.5×Upper Limit of Normal (ULN) (for patients with Gilbert syndrome, total bilirubin \<3.0×ULN with direct bilirubin within normal range);
• Serum creatinine \<1.5×ULN;
• Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) ≤2.5×ULN (≤5×ULN if there is liver involvement).