Rimegepant Plus Glofitamab and CD19 CAR-T Therapy in R/R LBCL

Official title

A Study to Evaluate the Efficacy and Safety of Rimegepant Plus Glofitamab and CD19 CAR-T Cell Therapy in Patients With High-Risk Relapsed/Refractory Large B-Cell Lymphoma

Overview

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.

Interventions

• Drug Rimegepant
  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.
• Drug Glofitamab
  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.
• Drug Obinutuzumab
  Obinutuzumab will be administered intravenously at 1000 mg on Cycle 1 Day 1 as pretreatment before glofitamab.
• Biological CD19 CAR-T Cell Therapy
  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.
• Drug Fludarabine
  Fludarabine will be administered as part of lymphodepleting chemotherapy before CD19 CAR-T cell infusion.
• Drug Cyclophosphamide
  Cyclophosphamide will be administered as part of lymphodepleting chemotherapy before CD19 CAR-T cell infusion.

Primary outcome measures

• Complete Response Rate at 6 Months [Time frame: 6 months after CAR-T cell infusion]

Secondary outcome measures (7)

• Objective Response Rate [Time frame: Up to 24 months]
• Complete Response Rate at Day 28 [Time frame: Day 28 after CAR-T cell infusion]
• Complete Response Rate at 3 Months [Time frame: 3 months after CAR-T cell infusion]
• Progression-Free Survival [Time frame: Up to 24 months]
• Duration of Response [Time frame: Up to 24 months]
• Overall Survival [Time frame: Up to 24 months]
• Adverse Events [Time frame: Up to 24 months]

Eligibility criteria

Inclusion criteria

• Able to understand and voluntarily sign the written informed consent form.
• Age 18 years or older.
• Histologically confirmed large B-cell lymphoma with CD19 and CD20 expression.
• Relapsed or refractory disease after at least one prior line of systemic therapy.
• Prior treatment must have included an anthracycline-containing chemotherapy regimen and an anti-CD20 monoclonal antibody.
• Considered suitable by the investigator to receive glofitamab and CD19 CAR-T cell therapy.
• Presence of at least one high-risk feature, including extranodal involvement, bulky disease, or TP53 abnormality.
• ECOG performance status of 0 to 2.
• Life expectancy of at least 12 weeks.
• Adequate bone marrow, hepatic, renal, pulmonary, and cardiac function as determined by the investigator.
• Participants of reproductive potential must agree to use effective contraception during the study period.
• Able and willing to comply with the study protocol, in the investigator's judgment.

Exclusion criteria

• History of hypersensitivity to any study treatment or related compounds.
• Active or uncontrolled infection requiring systemic treatment.
• History of allogeneic hematopoietic stem cell transplantation or organ transplantation.
• Uncontrolled or clinically significant viral infection as defined by the protocol.
• Known central nervous system involvement by lymphoma or clinically significant central nervous system disease that may interfere with study treatment or safety assessment.
• Severe or uncontrolled cardiovascular disease.
• Severe autoimmune disease or immune-mediated disease that may interfere with study treatment or safety assessment.
• Known or suspected history of hemophagocytic lymphohistiocytosis.
• Recent thromboembolic event before screening.
• History of another malignancy within 5 years before screening, except adequately treated carcinoma in situ or non-melanoma skin cancer.
• Receipt of prohibited anticancer therapy, immunosuppressive therapy, live attenuated vaccine, or other prohibited treatment within the protocol-specified period before enrollment.
• Pregnant or breastfeeding women, or participants planning pregnancy during the study period.
• Concurrent participation in another interventional clinical trial.
• Need for prohibited concomitant medications that cannot be discontinued or substituted.
• Any condition that, in the investigator's judgment, makes the participant unsuitable for study treatment or study participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai

Identifiers

NCT: NCT07613788 · RIME-CART

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗