Glofitamab: Glofitamab is administered as monotherapy or in combination with investigator-selected agents (including but not limited to chemotherapy, ADCs, BTK inhibitors, etc.) for 2 cycles.
Chimeric Antigen Receptor T Cells (CAR-T): After two cycles of glofitamab-based salvage therapy, single-target or dual-target CAR-T cells directed against CD19, CD20, and/or CD22 are infused following lymphodepleting (fludarabine + cyclophosphamide) or myeloablative conditioning, at a dose of 2-4 × 10⁶/kg.
Study summary
This study consists of two sequential treatment phases. In the first phase, patients with r/r aggressive B-NHL receive two cycles of glofitamab ± investigator-selected agents. In the second phase, patients eligible for CAR-T monotherapy undergo FC lymphodepletion followed by CAR-T infusion (2-4×10⁶/kg), while those eligible for CAR-T+ASCT receive conditioning chemotherapy with PBSC reinfusion on day 0 and CAR-T administration (2-4×10⁶/kg) on day +3 (±1). Patients demonstrating Deauville 4-5 or ctDNA positivity at day 28 post-CAR-T infusion subsequently receive four cycles of glofitamab consolidation therapy.
Eligibility
Sex
ALL
Min age
18 Years
Max age
65 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
complete response rate after CAR-T±ASCT — From CAR-T±ASCT administration until 1 year post-treatment The complete response (CR) rate after CAR-T±ASCT is defined as the proportion of subjects achieving CR following CAR-T with or without ASCT.
Trial sites (1)
Facility
City
Region
Status
Institute of Hematology & Blood Diseases Hospital
Tianjin
China
Recruiting
More Institute of Hematology & Blood Diseases Hospital, China trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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