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

NCT06996132 | Recruiting Phase 2

• 1 other identifier: IIT2025054
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Relapsed or Refractory Aggressive B-cell Lymphoma

Keywords

Glofitamab; CAR T-cell therapy; autologous stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• complete response rate after CAR-T±ASCT

  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.

  From CAR-T±ASCT administration until 1 year post-treatment

Secondary Outcomes (5)

• overall response rate after CAR-T±ASCT

  From CAR-T±ASCT administration until 1 year post-treatment

• complete response rate before CAR-T±ASCT

  From the initiation of glofitamab-based therapy until ≤14 days prior to the start of FC lymphodepleting therapy or myeloablative conditioning.

• overall response rate before CAR-T±ASCT

  From the initiation of glofitamab-based therapy until ≤14 days prior to the start of FC lymphodepleting therapy or myeloablative conditioning.

• progression free survival-total (PFS-t）

  through 2 years after initiation of study treatment

• progression free survival-CART (PFS-c）

  through 2 years after initiation of study treatment

Study Arms (1)

Glofitamab-based therapy followed by CAR-T ± ASCT

EXPERIMENTAL

Subjects will receive two cycles of glofitamab-based therapy, followed by either CAR-T cell therapy alone or in combination with ASCT.

Drug: Glofitamab; Drug: Chimeric Antigen Receptor T Cells (CAR-T)

Interventions

Glofitamab DRUG

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.

Glofitamab-based therapy followed by CAR-T ± ASCT

Chimeric Antigen Receptor T Cells (CAR-T) DRUG

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.

Glofitamab-based therapy followed by CAR-T ± ASCT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Relapsed or refractory disease, meeting criteria for one of the following cohorts:
• Cohort 1 (Relapsed/Refractory Disease):
• ≥2 prior lines of therapy (including both anti-CD20 monoclonal antibody and anthracycline-based chemotherapy) with documented progression following last treatment; OR
• 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.
• Age ≥18 years and ≤65 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Hematologic parameters at screening must meet the following (unless due to bone marrow involvement):

You may not qualify if:

• Confirmed primary central nervous system lymphoma;
• Prior autologous or allogeneic hematopoietic stem cell transplantation;
• Active HBV or HCV infection, defined as HBV-DNA or HCV-RNA levels above the upper limit of detection.
• Uncontrolled comorbidities include infectious diseases, cardiovascular/cerebrovascular disorders, coagulopathies, and connective tissue diseases.
• History of epilepsy or other central nervous system disorders;
• Pregnancy or lactation;
• HIV infection;
• History of other malignancies unless:
• Disease-free for ≥5 years, or
• 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
• Other conditions deemed ineligible by investigators.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, 022, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

glofitamab; Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Dehui Zou

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

WEI LIU

CONTACT

86-022-23608461; liuwei@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: May 30, 2025
• Study Start: May 9, 2025
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: June 17, 2025

Record last verified: 2025-05

Locations

CN (1)