This study will test whether anti-EBV autologous TCR-T cell injection is safe and effective for patients with relapsed or refractory EBV-positive lymphoma who have HLA-A11:01. Researchers will look at safety, tolerability, and the maximum tolerated dose or recommended dose for future studies. The study will also measure how the infused TCR-T cells expand and persist in the body, changes in EBV DNA levels and T-cell subgroups in the blood, and whether the treatment shows early signs of clinical benefit. Researchers will also explore whether the treatment causes an immune response against the infused cells.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
After signing the informed consent form and completing screening according to the inclusion/exclusion criteria, eligible subjects will be sequentially assigned to the following dose cohorts of TCR-T cells (single administration): 1×10⁶ TCR-T cells/kg, 2.5×10⁶ TCR-T cells/kg, 5×10⁶ TCR-T cells/kg, and 10×10⁶ TCR-T cells/kg. The first dose cohort (1×10⁶ TCR-T cells/kg) will use a rapid titration approach. If no significant safety issues occur within 28 days after infusion-defined as ≥Grade 3 non-hematologic toxicity, Grade 4 hematologic toxicity lasting more than 28 days (excluding disease- or chemotherapy-related causes), ≥Grade 2 neurotoxicity, or ≥Grade 3 cytokine release syndrome (CRS)-the next dose cohort will be initiated. If a dose-limiting toxicity (DLT) occurs, evaluation will be performed after 6 subjects have been treated. The subsequent three dose cohorts will follow a "3+3" dose-escalation design, with 3-6 subjects per cohort receiving a single infusion. For subjects in th
Shanghai General Hospital
Shanghai, China
RECRUITINGDose-Limiting Toxicity (DLT)
To evaluate the incidence of dose-limiting toxicities (DLTs) of anti-EBV TCR-T cell injection in subjects with relapsed/refractory EBV-positive HLA-A11:01 lymphoma.
Time frame: treatment cycle (Day 1 to Day 28)
Maximum Tolerated Dose (MTD)
Determination of the maximum tolerated dose of anti-EBV TCR-T cell injection.
Time frame: From Day 1 of treatment until the end of the dose-escalation phase
Recommended Phase 2 Dose (RP2D)
Determination of the recommended dose for the expansion study based on safety, tolerability, and MTD.
Time frame: At the completion of the dose-escalation phase
Expansion and persistence of EBV TCR-T cells
To evaluate the in vivo expansion and persistence of anti-EBV TCR-T cells after infusion
Time frame: From Day 1 of infusion up to 24 months
EBV DNA copies in peripheral blood
To evaluate the EBV DNA copy number in peripheral blood after infusion of anti-EBV TCR-T cells.
Time frame: From Day 1 of infusion up to 24 months
Changes in T-cell subsets in peripheral blood
To evaluate the changes in peripheral blood T-cell subsets after infusion of anti-EBV TCR-T cells.
Time frame: From Day 1 of infusion up to 24 months
Objective Response Rate (ORR)
Proportion of subjects achieving complete response (CR) or partial response (PR) following treatment with anti-EBV TCR-T cells.
Time frame: At 3 months and 6 months after infusion
Duration of Response (DOR)
Duration of response in subjects with relapsed/refractory EBV-positive lymphoma treated with anti-EBV TCR-T cells.
Time frame: From the first documented response (CR or PR) until disease progression/relapse or death, up to 24 months
Progression-Free Survival (PFS)
Progression-free survival following anti-EBV TCR-T cell treatment.
Time frame: From infusion until documented disease progression or death, up to 24 months
Overall Survival (OS)
Overall survival following anti-EBV TCR-T cell treatment.
Time frame: From infusion until death from any cause, up to 24 months
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