Relapsed/Refractory Large B-cell Lymphoma (LBCL)
Conditions
Brief summary
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
DRUGRimegepant
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.
DRUGGlofitamab
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.
DRUGObinutuzumab
Obinutuzumab will be administered intravenously at 1000 mg on Cycle 1 Day 1 as pretreatment before glofitamab.
BIOLOGICALCD19 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.
DRUGFludarabine
Fludarabine will be administered as part of lymphodepleting chemotherapy before CD19 CAR-T cell infusion.
DRUGCyclophosphamide
Cyclophosphamide will be administered as part of lymphodepleting chemotherapy before CD19 CAR-T cell infusion.
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate at 6 Months | 6 months after CAR-T cell infusion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 24 months | Objective response rate is defined as the proportion of participants who achieve complete response or partial response. |
| Complete Response Rate at Day 28 | Day 28 after CAR-T cell infusion | 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. |
| Complete Response Rate at 3 Months | 3 months after CAR-T cell infusion | 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. |
| Progression-Free Survival | Up to 24 months | Progression-free survival is defined as the time from randomization to disease progression or death from any cause, whichever occurs first. |
| Duration of Response | Up to 24 months | Duration of response is defined as the time from the first documented response to disease progression or death from any cause, whichever occurs first. |
| Overall Survival | Up to 24 months | Overall survival is defined as the time from randomization to death from any cause. |
| Adverse Events | Up to 24 months | Incidence and severity of adverse events will be assessed throughout the study. |
Countries
China
Contacts
CONTACTWeili Zhao
CONTACTRong Shen
Outcome results
None listed