EBV-targeted T-cell therapy for persistent EBV DNAemia after allogeneic transplant

An Exploratory Clinical Study of EBV-TCR-T Cell Injection for the Treatment of EBV DNAemia After Allogeneic Hematopoietic Stem Cell Transplantation

This treatment will try infusing EBV-specific TCR-engineered T cells into adults with persistent or rising EBV DNA after an allogeneic stem cell transplant to see if the virus clears and the therapy is safe.

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
• Locations: 1 site (Beijing)
• Trial ID: NCT07368634 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm dose-escalation trial administers EBV-specific TCR-engineered T cells manufactured from the patient or an appropriate donor via intravenous infusion. Participants may receive up to three weekly infusions at escalating dose levels (1×10^5, 5×10^5, 1×10^6 cells/kg) with dose escalation guided by predefined dose-limiting toxicities to identify a tolerated or optimal biologic dose. Key outcomes include safety, adverse events, EBV DNA clearance, and pharmacokinetic/pharmacodynamic profiling of the infused cells. The study plans to enroll approximately 4–18 adults with EBV DNAemia after allo-HSCT at a single center.

Who should consider this trial

Good fit: Adults (≥18 years) who underwent allogeneic hematopoietic stem cell transplantation and have persistent or increasing EBV DNAemia despite standard management, with ECOG 0–2 and adequate organ function, are the intended candidates.

Not a fit: Patients with active EBV-associated lymphoproliferative disorder needing immediate chemotherapy, uncontrolled non-EBV infections, severe autoimmune disease on systemic immunosuppression, or uncontrolled graft-versus-host disease on high-dose steroids are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the therapy could clear EBV DNAemia, lower the risk of progression to EBV-associated lymphoproliferative disease, and reduce the need for cytotoxic chemotherapy.

How similar studies have performed: Adoptive EBV-specific T-cell therapies, such as donor-derived EBV-specific cytotoxic T lymphocytes, have demonstrated success in treating or preventing PTLD, though TCR-engineered EBV-TCR-T products are less extensively tested in large clinical trials.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years at the time of enrollment.
* History of allogeneic hematopoietic stem cell transplantation.
* Presence of Epstein-Barr virus (EBV) DNAemia confirmed by quantitative polymerase chain reaction (qPCR) in peripheral blood.
* EBV DNAemia persisting or increasing despite standard management, as determined by the investigator.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Adequate organ function as defined by the study protocol.
* Ability to understand and willingness to sign written informed consent.

Exclusion Criteria:

* Diagnosis of EBV-associated lymphoproliferative disorder requiring immediate cytotoxic chemotherapy.
* Active, uncontrolled infection other than EBV.
* History of severe autoimmune disease requiring systemic immunosuppressive therapy.
* Uncontrolled graft-versus-host disease requiring high-dose systemic corticosteroids or other immunosuppressive treatment.
* Prior treatment with EBV-specific adoptive T cell therapy within a defined washout period.
* Known active malignancy other than EBV-related disease that may interfere with study participation.
* Pregnant or breastfeeding women.
* Any medical, psychological, or social condition that, in the opinion of the investigator, would interfere with safe participation in the study.

Where this trial is running

Beijing

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

Study contacts

• Study coordinator: Daihong Liu

Conditions Epstein-Barr Virus Infection; Post-Transplant Lymphoproliferative Disorder; EBV DNAemia; TCR-T Cell Therapy; Dose Escalation Study