This study is designed to evaluate the efficacy and safety of rimegepant in combination with glofitamab and CD19 CAR-T cell therapy in patients with high-risk relapsed/refractory large B-cell lymphoma. Eligible patients will be randomized to receive glofitamab plus CD19 CAR-T cell therapy with or without rimegepant. The primary endpoint is complete response rate at 6 months after CAR-T cell infusion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Rimegepant will be administered orally at 75 mg every other day from the first day of lymphodepleting chemotherapy until Day 90 after CAR-T cell infusion.
Glofitamab will be administered intravenously with step-up dosing. Participants will receive 2.5 mg on Cycle 1 Day 8, 10 mg on Cycle 1 Day 15, and 30 mg on Cycle 2 Day 1. Participants with CR, PR, or SD after CAR-T cell infusion may continue glofitamab consolidation at 30 mg on Day 1 of each 21-day cycle for four cycles.
Obinutuzumab will be administered intravenously at 1000 mg on Cycle 1 Day 1 as pretreatment before glofitamab.
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, China, China
Complete Response Rate at 6 Months
Complete response rate at 6 months is defined as the proportion of participants who achieve complete response at 6 months after CAR-T cell infusion.
Time frame: 6 months after CAR-T cell infusion
Objective Response Rate
Objective response rate is defined as the proportion of participants who achieve complete response or partial response.
Time frame: Up to 24 months
Complete Response Rate at Day 28
Complete response rate at Day 28 is defined as the proportion of participants who achieve complete response at Day 28 after CAR-T cell infusion.
Time frame: Day 28 after CAR-T cell infusion
Complete Response Rate at 3 Months
Complete response rate at 3 months is defined as the proportion of participants who achieve complete response at 3 months after CAR-T cell infusion.
Time frame: 3 months after CAR-T cell infusion
Progression-Free Survival
Progression-free survival is defined as the time from randomization to disease progression or death from any cause, whichever occurs first.
Time frame: Up to 24 months
Duration of Response
Duration of response is defined as the time from the first documented response to disease progression or death from any cause, whichever occurs first.
Time frame: Up to 24 months
Overall Survival
Overall survival is defined as the time from randomization to death from any cause.
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Participants will receive CD19-directed CAR-T cell therapy after lymphodepleting chemotherapy. The specific CAR-T product and dose will be determined according to the approved product label, institutional standard practice, and investigator discretion.
Fludarabine will be administered as part of lymphodepleting chemotherapy before CD19 CAR-T cell infusion.
Cyclophosphamide will be administered as part of lymphodepleting chemotherapy before CD19 CAR-T cell infusion.
Time frame: Up to 24 months
Adverse Events
Incidence and severity of adverse events will be assessed throughout the study.
Time frame: Up to 24 months