CAR T-cell Therapy in Combination With Glofitamab for Relapsed/Refractory Large B-Cell Lymphoma With High-Risk Prognostic Factors

NCT ID: NCT06567366

Last Updated: 2024-08-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2027-09-30

Brief Summary

The aim of this study is to evaluate the efficacy and safety of CAR T-cell therapy in combination with glofitamab for the treatment of relapsed/refractory large B-cell lymphoma with high-risk prognostic factors.

Conditions

Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAR T-cell therapy in combination with Glofitamab

After undergoing leukapheresis, participants will receive treatment in the following procedure.

Bridging Phase:

All participants will receive two cycles of Glofitamab treatment. On Day 1 of Cycle 1, patients will receive 1000 mg of Obinutuzumab as pretreatment.

CAR-T Treatment Phase:

Participants will receive lymphodepletion therapy with the FLU/CY regimen on Day -5 through Day -3. Participants will receive the CAR T-cell infusion on Day 0.

Consolidation Phase:

Treatment based on the response assessment at Day 28 after CAR T-cell infusion: participants who attained complete response (CR) at Day 28 will not receive additional Glofitamab treatment, while those attained partial response (PR), stable disease (SD), or progressive disease (PD) will receive additional four cycles of Glofitamab.

Group Type: EXPERIMENTAL

CAR T-cell therapy

Intervention Type: BIOLOGICAL

Participants will receive CAR T-cell therapy via infusion on Day 0 (given as per treatment guidelines). Prior to CAR T-cell Therapy, participants will begin receiving lymphodepleting chemotherapy on Days -5 through -3 (given as per treatment guidelines).

Glofitamab

Intervention Type: DRUG

Glofitamab is given intravenously at a dose of 2.5mg over 4 hours on Cycle 1 Day 8.

Glofitamab is given intravenously at a dose of 10mg over 2 hours on Cycle 1 Day 15.

Glofitamab is given intravenously at a dose of 30mg over 2 hours on Day 1 of Cycles 2-6 (as relevant).

Obinutuzumab

Intervention Type: DRUG

Obinutuzumab pre-treatment is given intravenously at a dose of 1g on Cycle 1 Day 1.

Interventions

CAR T-cell therapy

Participants will receive CAR T-cell therapy via infusion on Day 0 (given as per treatment guidelines). Prior to CAR T-cell Therapy, participants will begin receiving lymphodepleting chemotherapy on Days -5 through -3 (given as per treatment guidelines).

Intervention Type: BIOLOGICAL

Glofitamab

Glofitamab is given intravenously at a dose of 2.5mg over 4 hours on Cycle 1 Day 8.

Glofitamab is given intravenously at a dose of 10mg over 2 hours on Cycle 1 Day 15.

Glofitamab is given intravenously at a dose of 30mg over 2 hours on Day 1 of Cycles 2-6 (as relevant).

Intervention Type: DRUG

Obinutuzumab

Obinutuzumab pre-treatment is given intravenously at a dose of 1g on Cycle 1 Day 1.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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 transformed follicular lymphoma
• Patients who have relapsed or are refractory to at least prior first-line therapy, including 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
• 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

Exclusion Criteria

• Hypersensitivity to any study drug or excipient
• History of allogeneic stem cell transplantation
• Patients with active viral hepatitis requiring treatment as determined by the investigator: chronic hepatitis B virus carriers with HBV DNA ≥ 500 IU/mL (2500 copies/mL) (HBV DNA testing only for patients who test positive for hepatitis B surface antigen or core antibody); patients who test positive for HCV RNA (HCV testing only for patients who test positive for HCV antibody)
• Presence of uncontrolled infection, cardio-cerebrovascular disease, coagulopathy, or autoimmune disease, etc
• History of HIV infection
• Presence or concurrence of other malignancies within the past 2 years, with the exception of cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors
• Previous anti-CD19 CAR-T therapy is not allowed
• Pregnant or lactating women
• Other uncontrollable medical condition that may interfere the participation of the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhao Weili

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shanghai Ruijin Hospital

Shanghai, , China

Countries

China

Central Contacts

Weili Zhao

Role: CONTACT

zwl_trial@163.com

008602164370045

Other Identifiers

Glofit-CART

Identifier Type: -

Identifier Source: org_study_id