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

NCT06567366 | Not Yet Recruiting Phase 2

• 1 other identifier: Glofit-CART
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate

  CR rate is defined as the percentage of participants achieving CR per the Lugano Classification as determined by study investigators

  Up to 2 years

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Up to 2 years

• Duration of Response (DoR)

  Up to 2 years

• Progression-Free Survival (PFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

• Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)

  Up to 2 years

Study Arms (1)

CAR T-cell therapy in combination with Glofitamab

EXPERIMENTAL

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.

Biological: CAR T-cell therapy; Drug: Glofitamab; Drug: Obinutuzumab

Interventions

CAR T-cell therapy 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).

CAR T-cell therapy in combination with Glofitamab

Glofitamab 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).

CAR T-cell therapy in combination with Glofitamab

Obinutuzumab DRUG

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

CAR T-cell therapy in combination with Glofitamab

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Shanghai Ruijin Hospital

Shanghai, China

Location

MeSH Terms

Interventions

Immunotherapy, Adoptive; glofitamab; obinutuzumab

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Weili Zhao

CONTACT

008602164370045; zwl_trial@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: August 20, 2024
• First Posted: August 22, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: August 22, 2024

Record last verified: 2024-08

Locations

CN (1)