A Single-Center, Prospective Study Evaluating the Efficacy and Safety of CAR T-cell Therapy in Combination With Glofitamab in the Treatment of Relapsed/Refractory Large B-Cell Lymphoma With High-Risk Prognostic Factors
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Ruijin Hospital
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Complete Response (CR) Rate
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: CAR T-cell therapy (Biological)
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.
Intervention: Glofitamab (Drug)
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.
Intervention: Obinutuzumab (Drug)
Outcomes
Primary Outcomes
Complete Response (CR) Rate
Time Frame: Up to 2 years
CR rate is defined as the percentage of participants achieving CR per the Lugano Classification as determined by study investigators
Secondary Outcomes
- 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)
Investigators
Zhao Weili
Prof.
Ruijin Hospital