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

November 29, 2025 updated by: Xianmin Song, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

The Safety and Efficacy of Anti-EBV Autologous TCR-T Cell Injection for Treating Relapsed/Refractory EBV-positive Lymphoma Patients With HLA-A11:01

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xianmin Song, Doctor
  • Phone Number: +86 18918029692
  • Email: shongxm@139.com

Study Locations

  • China
      • Shanghai, China
        • Recruiting
        • Shanghai General Hospital
        • Contact:
          • Xianmin Song, Doctor
          • Phone Number: +86 18918029692
          • Email: shongxm@139.com
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 18-70 years, male or female.
  2. HLA genotype at locus A is 11:01.

  3. Disease diagnosis and status:

    1. 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.

    2. Disease types include but are not limited to:

      NK/T-cell lymphoma (NK/TCL); Peripheral T-cell lymphoma (PTCL); Other types.

    3. Definition of relapse: appearance of new lesions at the primary site or other sites after achieving complete remission (CR).
    4. 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.

  4. 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).

  5. Measurable disease: At least one measurable lesion according to the 2014 Lymphoma Response Evaluation Criteria:

    1. Nodal lesions: longest diameter >15 mm on contrast-enhanced CT, MRI, or PET-CT;
    2. 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.

  6. Adequate organ function, defined as:

    1. Hematologic: absolute neutrophil count ≥1×10⁹/L; hemoglobin ≥70 g/L; platelet count ≥50×10⁹/L;
    2. Hepatic: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × the upper limit of normal (ULN), and total bilirubin (TBIL) ≤ 1.5 × ULN (except when liver function abnormalities are attributable to the underlying disease);
    3. Renal: serum creatinine ≤1.5× ULN;
    4. Cardiac: left ventricular ejection fraction (LVEF) ≥50%;
    5. Coagulation: fibrinogen ≥1.0 g/L; activated partial thromboplastin time (APTT) ≤1.5× ULN; prothrombin time (PT) ≤1.5× ULN.
  7. Expected survival >3 months.
  8. ECOG performance status <3.

  9. Contraception requirements:

    1. No pregnancy planned during the treatment period;
    2. Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the study and for 4 months after the end of treatment.
  10. Willingness to participate in the study, ability to sign informed consent, comply with the study protocol, and availability of peripheral venous access for lymphocyte collection.

Exclusion Criteria:

Subjects meeting any of the following conditions will not be eligible for enrollment:

  1. History of other malignancies, except for:

    1. Basal cell carcinoma of the skin;
    2. Squamous cell carcinoma of the skin;
    3. Superficial bladder cancer;
    4. Carcinoma in situ of the cervix;
    5. Gastrointestinal mucosal carcinoma in situ;
    6. Other malignancies considered acceptable by the investigator (must have received curative treatment with no recurrence within the past 5 years).
  2. 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.
  3. Pregnant or breastfeeding women.
  4. Presence of severe medical conditions such as intracranial hypertension, impaired consciousness, respiratory failure, or disseminated intravascular coagulation (DIC).

  5. 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%.

  6. Known active infections or positive screening results for:

    1. Hepatitis B virus (HBV): HBsAg positive, or HBcAb positive with HBV-DNA above the detection limit of the study center;
    2. Hepatitis C virus (HCV): HCV antibody positive and HCV RNA ≥ upper limit of normal (ULN);
    3. Human immunodeficiency virus (HIV) or Treponema pallidum (syphilis) antibody positive;
    4. Active tuberculosis (TB) (must be excluded by chest X-ray, sputum test, and clinical symptoms) or history of active TB;
    5. Severe acute or chronic infections requiring systemic treatment.
  7. Active central nervous system (CNS) disease (e.g., tumor metastasis, infection, demyelinating disease), including untreated lesions, progressive disease on imaging or symptoms requiring urgent intervention, or requiring high-dose immunosuppressive therapy for control.
  8. Receiving systemic corticosteroid therapy prior to screening and judged by the investigator to require long-term systemic corticosteroid treatment during the study (excluding inhaled or topical use); or receiving systemic corticosteroid treatment within 72 hours before cell infusion (excluding inhaled or topical use).
  9. Presence of graft-versus-host disease (GVHD), defined as grade ≥2 acute GVHD or moderate/severe chronic GVHD, or current use of immunosuppressive therapy.
  10. History of severe allergic reactions to drugs or excipients required in this study, or history of allergy to tocilizumab.
  11. Any condition that, in the opinion of the investigator, makes the subject unsuitable for study participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EBV-TCR-T
Drug: EBV TCR-T

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-Limiting Toxicity (DLT)
Time Frame: treatment cycle (Day 1 to Day 28)
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)
Time Frame: From Day 1 of treatment until the end of the dose-escalation phase
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)
Time Frame: At the completion of the dose-escalation phase
Determination of the recommended dose for the expansion study based on safety, tolerability, and MTD.
At the completion of the dose-escalation phase

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expansion and persistence of EBV TCR-T cells
Time Frame: From Day 1 of infusion up to 24 months
To evaluate the in vivo expansion and persistence of anti-EBV TCR-T cells after infusion
From Day 1 of infusion up to 24 months
EBV DNA copies in peripheral blood
Time Frame: From Day 1 of infusion up to 24 months
To evaluate the EBV DNA copy number in peripheral blood after infusion of anti-EBV TCR-T cells.
From Day 1 of infusion up to 24 months
Changes in T-cell subsets in peripheral blood
Time Frame: From Day 1 of infusion up to 24 months
To evaluate the changes in peripheral blood T-cell subsets after infusion of anti-EBV TCR-T cells.
From Day 1 of infusion up to 24 months
Objective Response Rate (ORR)
Time Frame: At 3 months and 6 months after infusion
Proportion of subjects achieving complete response (CR) or partial response (PR) following treatment with anti-EBV TCR-T cells.
At 3 months and 6 months after infusion
Duration of Response (DOR)
Time Frame: From the first documented response (CR or PR) until disease progression/relapse or death, up to 24 months
Duration of response in subjects with relapsed/refractory EBV-positive lymphoma treated with anti-EBV TCR-T cells.
From the first documented response (CR or PR) until disease progression/relapse or death, up to 24 months
Progression-Free Survival (PFS)
Time Frame: From infusion until documented disease progression or death, up to 24 months
Progression-free survival following anti-EBV TCR-T cell treatment.
From infusion until documented disease progression or death, up to 24 months
Overall Survival (OS)
Time Frame: From infusion until death from any cause, up to 24 months
Overall survival following anti-EBV TCR-T cell treatment.
From infusion until death from any cause, up to 24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic (PK) parameters
Time Frame: From Day 1 to Day 28 after infusion
Maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the curve (AUC0-28d) of anti-EBV TCR-T cells in peripheral blood.
From Day 1 to Day 28 after infusion
Pharmacodynamic (PD) parameters
Time Frame: From Day 1 of infusion up to 24 months
plasma cytokine levels at multiple time points after infusion.
From Day 1 of infusion up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2025

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

September 1, 2029

Study Registration Dates

First Submitted

August 31, 2025

First Submitted That Met QC Criteria

August 31, 2025

First Posted (Estimated)

September 9, 2025

Study Record Updates

Last Update Posted (Actual)

December 2, 2025

Last Update Submitted That Met QC Criteria

November 29, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHSYXY-EBV-TCR-T-202505

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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