Status:
RECRUITING
Safety and Efficacy of Anti-EBV Autologous TCR-T Cell Injection in Relapsed/Refractory EBV-Positive Lymphoma
Lead Sponsor:
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Conditions:
NK/T-cell Lymphoma
Peripheral T-cell Lymphoma (PTCL)
Eligibility:
All Genders
18-70 years
Phase:
EARLY_PHASE1
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...
Eligibility Criteria
Inclusion
- 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:
- Hematologic: absolute neutrophil count ≥1×10⁹/L; hemoglobin ≥70 g/L; platelet count ≥50×10⁹/L;
- 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);
- Renal: serum creatinine ≤1.5× ULN;
- Cardiac: left ventricular ejection fraction (LVEF) ≥50%;
- Coagulation: fibrinogen ≥1.0 g/L; activated partial thromboplastin time (APTT) ≤1.5× ULN; prothrombin time (PT) ≤1.5× ULN.
- Expected survival \>3 months.
- ECOG performance status \<3.
- Contraception requirements:
- No pregnancy planned during the treatment period;
- 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.
- 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
- 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;
- Hepatitis C virus (HCV): HCV antibody positive and HCV RNA ≥ upper limit of normal (ULN);
- Human immunodeficiency virus (HIV) or Treponema pallidum (syphilis) antibody positive;
- Active tuberculosis (TB) (must be excluded by chest X-ray, sputum test, and clinical symptoms) or history of active TB;
- Severe acute or chronic infections requiring systemic treatment.
- 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.
- 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).
- Presence of graft-versus-host disease (GVHD), defined as grade ≥2 acute GVHD or moderate/severe chronic GVHD, or current use of immunosuppressive therapy.
- History of severe allergic reactions to drugs or excipients required in this study, or history of allergy to tocilizumab.
- Any condition that, in the opinion of the investigator, makes the subject unsuitable for study participation.
Key Trial Info
Start Date :
September 20 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 1 2029
Estimated Enrollment :
24 Patients enrolled
Trial Details
Trial ID
NCT07162012
Start Date
September 20 2025
End Date
September 1 2029
Last Update
December 2 2025
Active Locations (1)
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1
Shanghai General Hospital
Shanghai, China