EBV-specific T-cell infusions for EBV-positive lymphoma and PTLD

Exploratory Clinical Study of EBV-AST Cell Injection for the Treatment of EBV-Associated Lymphoproliferative Disorders

This trial will test whether infusions of EBV-specific cytotoxic T cells (EBV-AST) are safe and can help adults with EBV-associated lymphoproliferative disorders, including post-transplant lymphoproliferative disease and EBV-positive lymphomas.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07450391 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm, dose-escalation Phase 1/2 study delivering intravenously three possible infusions of EBV-AST every two weeks at one of three escalating dose levels. EBV-AST are antigen-specific cytotoxic T lymphocytes generated ex vivo to target EBV-infected or EBV-antigen–expressing tumor cells. The primary goal is to determine safety, tolerability, and a biologically active dose using dose-limiting toxicity rules within 28 days of the first infusion. Secondary endpoints include preliminary tumor responses, EBV viral load outcomes, and cellular pharmacokinetics/pharmacodynamics.

Who should consider this trial

Good fit: Adults aged 18–75 with EBV-associated lymphoproliferative disorders or EBV-positive lymphoma who have relapsed/refractory disease or are unsuitable for standard therapy, have KPS ≥70, life expectancy ≥3 months, and carry at least one required HLA type (HLA-A*02:01, HLA-A*11:01, or HLA-A*24:02) are eligible.

Not a fit: Patients without a matching HLA type, with poor performance status or life expectancy under three months, or those who have effective standard treatment options available are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, EBV-AST infusions could reduce EBV-infected tumor burden and restore EBV-specific immunity, potentially inducing remissions in patients with limited treatment options.

How similar studies have performed: Related adoptive EBV-specific T-cell therapies have demonstrated meaningful responses, especially in PTLD after transplant, although results in diverse EBV-positive lymphomas have been variable and optimization is ongoing.

Eligibility criteria

Inclusion Criteria:

1. Able to understand and voluntarily sign written informed consent.
2. Age 18 to 75 years, inclusive.
3. HLA genotype matches at least one of the following: HLA-A02:01, HLA-A11:01, or HLA-A\*24:02.
4. Karnofsky Performance Status (KPS) ≥ 70.
5. Life expectancy ≥ 3 months.
6. Diagnosed with EBV-associated lymphoproliferative disorders, including:
7. EBV infection-associated post-transplant lymphoproliferative disorder (PTLD) that is relapsed/refractory after at least first-line standard therapy; or
8. EBV-associated lymphoma confirmed by histology and/or cytology with EBER positivity (ISH/FISH), with no standard treatment available or not suitable for standard therapy, including but not limited to: EBV-positive DLBCL, EBV-positive NK/T-cell lymphoma, EBV-positive Hodgkin lymphoma, EBV-positive Burkitt lymphoma, EBV-positive nodal TFH lymphoma (AITL type), and EBV-positive primary cutaneous T-cell lymphoma, meeting protocol-defined relapsed/refractory criteria.
9. Absolute lymphocyte count ≥ 0.8 × 10\^9/L (except for PTLD participants).
10. Adequate organ and bone marrow function per protocol-defined criteria.
11. Participants of childbearing potential agree to use highly effective contraception throughout the study; women of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

1. Known hypersensitivity to the investigational product or its components.
2. Uncontrolled active graft-versus-host disease (GVHD) in PTLD participants.
3. Known primary immunodeficiency disorders (e.g., X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, chronic granulomatous disease, hyper-IgE syndrome).
4. Severe uncontrolled medical conditions that, in the investigator's judgment, make the participant unsuitable for enrollment.
5. Serious cardiac disease within 6 months prior to first infusion (e.g., myocardial infarction, severe/unstable angina, bypass surgery, NYHA class III-IV heart failure).
6. Chronic diseases requiring systemic immunosuppressants or systemic steroids (except local/inhaled steroids or physiologic replacement therapy).
7. History of other malignancy within the past 5 years, except carcinoma in situ (e.g., cervix, bladder, breast) or non-melanoma skin cancer.
8. Receipt of lymphocyte-based immunotherapy (e.g., CIK, DC, DC-CIK, LAK) within 3 months prior to consent.
9. Receipt of interferon or other targeted immunodeficiency drugs within 3 months prior to consent; prior high-dose IL-2 therapy.
10. Anti-cancer therapy within 14 days prior to consent (including chemotherapy or immunosuppressants/steroids); other cell therapy or live vaccines/attenuated vaccines or other investigational drugs within 28 days prior to consent; curative radiotherapy or major surgery within 4 weeks, or palliative local radiotherapy within 2 weeks prior to consent.
11. Prior immune therapy-associated ≥ Grade 3 immune-related adverse events (irAEs).
12. Unresolved toxicity from prior therapy \> Grade 1 (except alopecia any grade; peripheral sensory neuropathy ≤ Grade 2).
13. Uncontrolled psychiatric or neurologic disorders; drug abuse or alcohol dependence.
14. Positive HIV antibody; positive Treponema pallidum antibody; active hepatitis B (HBsAg and/or HBeAg positive with HBV-DNA above ULN) or active hepatitis C (HCV-Ab positive and HCV-RNA positive).
15. Uncontrolled severe active infection or contagious disease (excluding EBV infection).
16. Pregnant or breastfeeding women.

Where this trial is running

Beijing, Beijing Municipality

• Chinese PLA General Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Daihong Liu

Conditions Epstein-Barr Virus-Associated Lymphoproliferative Disorders; EBV-Positive Lymphoma; EBV-associated lymphoproliferative disorder; EBV-positive lymphoma; Adoptive T-cell therapy; Antigen-specific T cells