Safety and Efficacy of Anti-EBV Autologous TCR-T Cell Injection in Relapsed/Refractory EBV-Positive Lymphoma

NCT07162012 | Recruiting Early Phase 1

• 1 other identifier: SHSYXY-EBV-TCR-T-202505
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

NK/T-cell Lymphoma; Peripheral T-cell Lymphoma (PTCL); DLBCL

Outcome Measures

Primary Outcomes (3)

• Dose-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.

  treatment cycle (Day 1 to Day 28)

• Maximum Tolerated Dose (MTD)

  Determination of the maximum tolerated dose of anti-EBV TCR-T cell injection.

  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.

  At the completion of the dose-escalation phase

Secondary Outcomes (7)

• Expansion and persistence of EBV TCR-T cells

  From Day 1 of infusion up to 24 months

• EBV DNA copies in peripheral blood

  From Day 1 of infusion up to 24 months

• Changes in T-cell subsets in peripheral blood

  From Day 1 of infusion up to 24 months

• Objective Response Rate (ORR)

  At 3 months and 6 months after infusion

• Duration of Response (DOR)

  From the first documented response (CR or PR) until disease progression/relapse or death, up to 24 months

Other Outcomes (2)

• Pharmacokinetic (PK) parameters

  From Day 1 to Day 28 after infusion

• Pharmacodynamic (PD) parameters

  From Day 1 of infusion up to 24 months

Study Arms (1)

EBV-TCR-T

EXPERIMENTAL

Drug: EBV TCR-T

Interventions

EBV TCR-T DRUG

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

EBV-TCR-T

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years, male or female.
• HLA genotype at locus A is 11:01.
• Disease diagnosis and status:
• Histologically or cytologically confirmed EBV-positive lymphoma (tumor tissue must be EBER-positive as confirmed by in situ hybridization \[ISH\] or fluorescence in situ hybridization \[FISH\]), with peripheral blood EBV viral load \>10³ copies/mL by quantitative real-time PCR.
• Disease types include but are not limited to:
• NK/T-cell lymphoma (NK/TCL); Peripheral T-cell lymphoma (PTCL); Other types.
• Definition of relapse: appearance of new lesions at the primary site or other sites after achieving complete remission (CR).
• Definition of refractory disease (meeting any of the following):
• No partial remission (PR) after ≥4 cycles of standard therapy; No complete remission (CR) after ≥6 cycles of therapy; Failure to achieve CR after autologous hematopoietic stem cell transplantation; If best response is progressive disease (PD) or treatment is discontinued due to PD, no minimum cycle requirement applies.
• Prior treatment requirements:
• a) For relapsed/refractory PTCL or NK/TCL, patients must have received at least one prior line of systemic therapy. For relapsed/refractory NK/TCL, patients must have received an asparaginase-containing regimen (patients with stage I/II nasal NK/TCL according to the CA staging system must have also received radiotherapy).
• Measurable disease: At least one measurable lesion according to the 2014 Lymphoma Response Evaluation Criteria:
• Nodal lesions: longest diameter \>15 mm on contrast-enhanced CT, MRI, or PET-CT;
• Extranodal lesions: longest diameter \>10 mm. For patients with bone-marrow-only involvement who have no measurable lesions on imaging, the presence of ≥5% lymphoma cells in bone marrow biopsy or flow cytometry can be considered an evaluable lesion.
• Adequate organ function, defined as:

You may not qualify if:

• Subjects meeting any of the following conditions will not be eligible for enrollment:
• History of other malignancies, except for:
• Basal cell carcinoma of the skin;
• Squamous cell carcinoma of the skin;
• Superficial bladder cancer;
• Carcinoma in situ of the cervix;
• Gastrointestinal mucosal carcinoma in situ;
• Other malignancies considered acceptable by the investigator (must have received curative treatment with no recurrence within the past 5 years).
• Recent anti-tumor therapy: less than 4 weeks since last anti-cancer therapy (radiotherapy, chemotherapy, targeted therapy, immunotherapy, or local therapy), or less than 2 weeks since palliative radiotherapy.
• Pregnant or breastfeeding women.
• Presence of severe medical conditions such as intracranial hypertension, impaired consciousness, respiratory failure, or disseminated intravascular coagulation (DIC).
• Severe organ dysfunction, including:
• NYHA class IV cardiac function; Child-Pugh class C liver function; Creatinine clearance \<60 mL/min (by Cockcroft-Gault formula); Baseline oxygen saturation \<92%.
• Known active infections or positive screening results for:
• Hepatitis B virus (HBV): HBsAg positive, or HBcAb positive with HBV-DNA above the detection limit of the study center;

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Shanghai General Hospital

Shanghai, China

RECRUITING

Related Publications (15)

• Chou CC, Tsao CF, Liao CK, You HL, Wang MC, Huang WT. Analysis of latent T-cell epitopes in Epstein-Barr virus isolated from extranodal nasal-type natural killer/T-cell lymphoma in Taiwanese population. Exp Mol Pathol. 2021 Feb;118:104577. doi: 10.1016/j.yexmp.2020.104577. Epub 2020 Nov 23.

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• Barros MHM, Alves PDS. Contribution of the Epstein-Barr virus to the oncogenesis of mature T-cell lymphoproliferative neoplasms. Front Oncol. 2023 Sep 14;13:1240359. doi: 10.3389/fonc.2023.1240359. eCollection 2023.

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• Hinrichs CS, Restifo NP. Reassessing target antigens for adoptive T-cell therapy. Nat Biotechnol. 2013 Nov;31(11):999-1008. doi: 10.1038/nbt.2725. Epub 2013 Oct 20.

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• Heslop HE, Slobod KS, Pule MA, Hale GA, Rousseau A, Smith CA, Bollard CM, Liu H, Wu MF, Rochester RJ, Amrolia PJ, Hurwitz JL, Brenner MK, Rooney CM. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2010 Feb 4;115(5):925-35. doi: 10.1182/blood-2009-08-239186. Epub 2009 Oct 30.

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  PMID: 29920566 RESULT

• Lu TX, Liang JH, Miao Y, Fan L, Wang L, Qu XY, Cao L, Gong QX, Wang Z, Zhang ZH, Xu W, Li JY. Epstein-Barr virus positive diffuse large B-cell lymphoma predict poor outcome, regardless of the age. Sci Rep. 2015 Jul 23;5:12168. doi: 10.1038/srep12168.

  PMID: 26202875 RESULT

• Song CG, Huang JJ, Li YJ, Xia Y, Wang Y, Bi XW, Jiang WQ, Huang HQ, Lin TY, Li ZM. Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma in the Elderly: A Matched Case-Control Analysis. PLoS One. 2015 Jul 29;10(7):e0133973. doi: 10.1371/journal.pone.0133973. eCollection 2015.

  PMID: 26222726 RESULT

• Ok CY, Papathomas TG, Medeiros LJ, Young KH. EBV-positive diffuse large B-cell lymphoma of the elderly. Blood. 2013 Jul 18;122(3):328-40. doi: 10.1182/blood-2013-03-489708. Epub 2013 May 6.

  PMID: 23649469 RESULT

• Healy JA, Dave SS. The Role of EBV in the Pathogenesis of Diffuse Large B Cell Lymphoma. Curr Top Microbiol Immunol. 2015;390(Pt 1):315-37. doi: 10.1007/978-3-319-22822-8_13.

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• Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, Millenson MM, Cohen AD, Schuster SJ, Lebovic D, Dhodapkar M, Avigan D, Chapuy B, Ligon AH, Freeman GJ, Rodig SJ, Cattry D, Zhu L, Grosso JF, Bradley Garelik MB, Shipp MA, Borrello I, Timmerman J. Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. J Clin Oncol. 2016 Aug 10;34(23):2698-704. doi: 10.1200/JCO.2015.65.9789. Epub 2016 Jun 6.

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• Kuppers R, Engert A, Hansmann ML. Hodgkin lymphoma. J Clin Invest. 2012 Oct;122(10):3439-47. doi: 10.1172/JCI61245. Epub 2012 Oct 1.

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MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell; Lymphoma, T-Cell, Peripheral

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Xianmin Song, Doctor

CONTACT

+86 18918029692; shongxm@139.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Hematology

Model Details: Using a rapid titration combined with a "3+3" design

Study Record Dates

• First Submitted: August 31, 2025
• First Posted: September 9, 2025
• Study Start: September 20, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: December 2, 2025

Record last verified: 2025-11

Locations

CN (1)