Glofitamab Combined With CAR-T Therapy in R/R DLBCL

NCT07326371 | Not Yet Recruiting Phase 2

• 1 other identifier: Glofit_peri_CART
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a single-center, open-label, prospective study aimed at evaluating the efficacy and safety of Glofitamab combined with CAR-T therapy in patients with high-risk relapsed/refractory large B-cell lymphoma.

Conditions

DLBCL - Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CRR)

  Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma

  Baseline up to the end of treatment (EOT) (approximately 4 months)

Secondary Outcomes (5)

• Overall Response Rate (ORR)

  Baseline up to the EOT (approximately 4 months)

• Duration of Response (DoR)

  From the date of the first occurrence of a documented CR or partial response (PR) to the date of progression, relapse, or death from any cause, whichever occurs first (up to approximately 42 months)

• PFS

  From the start of treatment until the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (approximately 42 months)

• Overall Survival (OS)

  From the start of treatment until the date of death from any cause (approximately 42 months)

• Number of Participants with TEAEs

  Up to the end of the study (approximately 42 months)

Study Arms (1)

Glofit_CART

EXPERIMENTAL

After undergoing leukapheresis, patients will receive treatment in three phases: the bridging phase, the CAR-T treatment phase, and the consolidation phase. Bridging Phase: All patients will receive two cycles of Glofitamab treatment. On Day 1 of Cycle 1, patients will receive 1000 mg of Obinutuzumab as pretreatment. After the completion of Cycle 2, patients will undergo an assessment. CAR-T Treatment Phase: Participants will receive lymphodepletion therapy with the FLU/CY regimen from Day -5 to Day -3. On Day 0, patients will receive the CAR-T cell infusion. Consolidation Phase: Based on the efficacy assessment on Day 28, the subsequent treatment plan will be determined: Patients achieving complete response (CR) will not receive additional Glofitamab treatment. Patients with partial response (PR), stable disease (SD), or progressive disease (PD) will continue to receive Glofitamab treatment for four additional cycles.

Drug: Glofitamab; Drug: Obinutuzumab; Drug: Axicabtagene Ciloleucel; Drug: Relmacabtagene autoleucel (relma-cel)

Interventions

Obinutuzumab DRUG

Obinutuzumab IV infusion will be administered as per the schedule specified in the respective arm.

Glofit_CART

Axicabtagene Ciloleucel DRUG

Axicabtagene Ciloleucel IV infusion will be administered as per the schedule specified in the respective arm.

Glofit_CART

Glofitamab DRUG

Glofitamab IV infusion will be administered as per the schedule specified in the respective arm.

Glofit_CART

Relmacabtagene autoleucel (relma-cel) DRUG

Relmacabtagene autoleucel IV infusion will be administered as per the schedule specified in the respective arm.

Glofit_CART

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form
• Histologically confirmed large B==cell lymphoma with CD19 and CD20 expression, including diffuse large B==cell lymphoma (DLBCL) not otherwise specified (NOS); primary mediastinal large B==cell lymphoma (PMBCL); high==grade B==cell lymphoma (HGBL); and DLBCL transformed from follicular lymphoma
• Patients who have relapsed after at least one prior line of therapy or are refractory, including those who have received anthracycline==containing chemotherapy regimens and anti==CD20 monoclonal antibody therapy
• Patients must be willing to receive CAR==T and Glofitamab therapy and be deemed suitable for CAR==T and Glofitamab treatment by the investigator
• Presence of at least one high==risk prognostic factor: (1) extranodal involvement; (2) maximum tumor diameter \> 4 cm; (3) TP53 mutation
• No CNS involvement
• ECOG Performance Status of 0, 1, or 2
• Life expectancy ≥12 weeks
• Adequate hematologic function (unless due to underlying disease, such as extensive bone marrow involvement, or secondary to lymphoma==related splenomegaly as determined by the investigator, but transfusion of blood products is allowed) and adequate liver, renal, pulmonary, and cardiac function, defined as follows:
• Neutrophil count ≥ 1.0 × 10\^9/L, platelet count ≥ 50 × 10\^9/L, lymphocyte count ≥ 0.1 × 10\^9/L
• ALT/AST ≤ 2.5 × ULN and total bilirubin \< 1.5 × ULN (except for participants with Gilbert's syndrome or lymphoma involvement of the liver)
• Creatinine clearance ≥ 30 mL/min
• Pulmonary function: ≤ CTCAE grade 1 dyspnea, oxygen saturation (SpO2) ≥ 92% on room air
• Cardiac function: LVEF ≥ 40%
• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiating study treatment. Women who are postmenopausal (defined as no menses for ≥ 12 months without an alternative medical cause) or have undergone surgical sterilization (removal of ovaries and/or uterus) are not required to undergo a pregnancy test

You may not qualify if:

• History of allergic reactions to compounds with similar chemical or biological composition to axi==cel, relma==cel, glofitamab, obinutuzumab, or other drugs used in the study.
• Active or uncontrolled infections requiring systemic therapy (including fungal, bacterial, viral, etc.)
• History of allogeneic hematopoietic stem cell transplantation
• History of organ transplantation
• Viral infections deemed uncontrollable by antiviral medications, as determined by the investigator, including:
• Active hepatitis B virus (HBV) infection with HBV DNA ≥ 500 IU/mL (2500 copies/mL)
• Positive hepatitis C virus (HCV) RNA test
• Positive human immunodeficiency virus antibody (HIV==Ab) test
• Positive Treponema pallidum antibody (TP==Ab) test
• Cytomegalovirus (CMV) DNA levels above the upper limit of normal
• Epstein==Barr virus (EBV) DNA levels above the upper limit of normal
• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Presence of brain metastases or active primary central nervous system lymphoma
• Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D, myocardial infarction within the last 6 months prior to the start of Cycle 1, unstable arrhythmias, or unstable angina
• Presence of severe genetic disorders or severe autoimmune diseases, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome==associated vascular thrombosis, Wegener's granulomatosis, Sjögren's syndrome, Guillain==Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis

Sponsors & Collaborators

• Ruijin Hospital: lead

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating

Interventions

glofitamab; obinutuzumab; axicabtagene ciloleucel; relmacabtagene autoleucel

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

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: December 26, 2025
• First Posted: January 8, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: January 8, 2026

Record last verified: 2025-07