Anti-EBV autologous TCR-T cell injection for relapsed or refractory EBV-positive lymphoma

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 trial will test whether injections of a patient's own anti-EBV TCR-T cells are safe and help adults (18–70) with relapsed or refractory EBV-positive lymphoma who have HLA-A11:01.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (other)
• Drugs / interventions: tocilizumab, chemotherapy, immunotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT07162012 on ClinicalTrials.gov

What this trial studies

This is an early-phase, dose-escalation trial giving autologous TCR-T cells engineered to target EBV in patients with relapsed or refractory EBV-positive lymphoma who carry HLA-A11:01. The study will escalate doses to define safety, tolerability, and the maximum tolerated or recommended dose for future studies. Investigators will monitor how the infused T cells expand and persist, measure changes in EBV DNA levels and T-cell subgroups in blood, and record any early signs of clinical benefit. The protocol requires tumor confirmation of EBV (EBER-positive by ISH/FISH) and a peripheral blood EBV viral load above 1,000 copies/mL.

Who should consider this trial

Good fit: Adults aged 18–70 with histologically confirmed EBV-positive lymphoma (EBER-positive) who are relapsed or refractory, have peripheral blood EBV >1,000 copies/mL, and are HLA-A11:01 are the intended participants.

Not a fit: Patients without HLA-A11:01, with EBV-negative tumors, with low or undetectable blood EBV levels, or who are medically unfit or outside the 18–70 age range are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this personalized T-cell therapy could reduce tumor burden and extend remissions by directing the patient's own immune cells against EBV-positive lymphoma cells.

How similar studies have performed: Related EBV-specific T-cell therapies (such as EBV-targeted CTLs) have produced clinical responses in some EBV-associated lymphomas, but autologous anti-EBV TCR-T approaches are relatively new and remain early in development.

Eligibility criteria

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.

Where this trial is running

Shanghai

• Shanghai General Hospital — Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Xianmin Song, Doctor

Conditions: NK/T-cell Lymphoma, Peripheral T-cell Lymphoma, DLBCL