Bispecific Antibody-Based Salvage Therapy Followed by CAR-T ± ASCT in R/R Aggressive B-Cell Lymphoma

Launched by INSTITUTE OF HEMATOLOGY & BLOOD DISEASES HOSPITAL, CHINA · May 28, 2025

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment approach for adults with relapsed or refractory aggressive B-cell lymphoma, which means their cancer has come back or hasn't responded well to previous treatments. The study has two main parts. In the first part, participants will receive two cycles of a treatment called glofitamab, possibly along with other medications chosen by their doctor. If they qualify for the second part, they will undergo a process called CAR-T therapy, which involves using their own immune cells to fight the cancer. Depending on their response, some may receive additional treatments to help strengthen the effect of the therapy.

To be eligible for this trial, participants need to be between 18 and 65 years old and have specific types of aggressive B-cell lymphoma that have not responded to at least two previous treatment regimens. They also need to have a good performance status, meaning they can carry out daily activities with minimal assistance. Throughout the study, participants will be closely monitored, and the goal is to determine how effective this treatment combination is in fighting the cancer and improving their health. If you or someone you know might qualify, it could be a valuable opportunity to access new treatment options.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Patients with relapsed/refractory aggressive B-cell lymphoma, including the following subtypes: diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), or transformed large B-cell lymphoma.
• 2. Relapsed or refractory disease, meeting criteria for one of the following cohorts:
• Cohort 1 (Relapsed/Refractory Disease):
• • 1. ≥2 prior lines of therapy (including both anti-CD20 monoclonal antibody and anthracycline-based chemotherapy) with documented progression following last treatment; OR
• 2. Failure of first-line immunochemotherapy (containing anti-CD20 antibody and anthracycline) defined by any of:
• • Relapse/progression within 12 months of treatment completion; OR
• • Progressive disease during first-line therapy; OR
• • Stable disease as best response after 4 cycles; OR
• • Partial response as best response after 6 cycles.
• Cohort 2 (Early Treatment Failure):
• • Persistent metabolic activity (Deauville 5) on PET-CT after 2 cycles of first-line immunochemotherapy; OR
• • Biopsy-proven residual disease following initial therapy.
• • 3. Age ≥18 years and ≤65 years.
• • 4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• 5. Hematologic parameters at screening must meet the following (unless due to bone marrow involvement):
• • Absolute neutrophil count (ANC) ≥1×10⁹/L,
• • Platelet count (PLT) ≥75×10⁹/L.
• 6. Biochemical parameters at screening must meet the following:
• • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN);
• • Total bilirubin (TBIL) ≤1.5×ULN (unless due to Gilbert's syndrome or non-hepatic causes);
• • Serum creatinine (Cr) ≤2×ULN OR creatinine clearance ≥40 mL/min.
• • 7. Left ventricular ejection fraction (LVEF) within institutional normal range by echocardiography.
• • 8. Baseline oxygen saturation \>92% on room air.
• • 9. Life expectancy ≥3 months as assessed by the investigator.
• Exclusion Criteria:
• • 1. Confirmed primary central nervous system lymphoma;
• • 2. Prior autologous or allogeneic hematopoietic stem cell transplantation;
• • 3. Active HBV or HCV infection, defined as HBV-DNA or HCV-RNA levels above the upper limit of detection.
• • 4. Uncontrolled comorbidities include infectious diseases, cardiovascular/cerebrovascular disorders, coagulopathies, and connective tissue diseases.
• • 5. History of epilepsy or other central nervous system disorders;
• • 6. Pregnancy or lactation;
• • 7. HIV infection;
• 8. History of other malignancies unless:
• • 1. Disease-free for ≥5 years, or
• 2. Previously cured of the following:
• • Non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma, or related localized cutaneous malignancies)
• • Carcinoma in situ of cervix
• • 9. Other conditions deemed ineligible by investigators.