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NCT Number: NCT05688241

EBV-Tscm Cytotoxic T Cells (CTLs) for EBV- Driven Lymphomas/ Diseases

In this multi-center open-label, non-randomized phase I/II intervention study three consecutive doses of donor-derived EBV Tscm-CTLs will be administered to 10 patients with treatment-refractory EBV lymphoma, diseases or PTLDs. EBV Tscm-CTLs will derive from hematopoietic cell transplant (HCT) or third-party donors.

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Key information

Conditions

EBV Lymphoma DNA Virus Infections Epstein-Barr Virus Infections Herpesviridae Infections Infections Post-transplant Lymphoproliferative Disease (PTLD) Tumor Virus Infections Virus Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University Hospital Basel, Klinik für Infektiologie und Spitalhygiene, Basel, Switzerland

About this study

Epstein Barr virus (EBV)-driven lymphomas and diseases are associated with poor prognosis. EBV proteins are recognized by T cells providing opportunities for EBV-specific T-cell therapy. Recent findings show that early differentiated T cells (T memory stem cells, Tscm) improve the prognosis in chronic viral diseases and are associated with effective tumor cell killing in melanoma patients. Tscm might be superior to highly differentiated T cells because of their longevity, robust proliferative potential, and capacity to reconstitute a wide T-cell receptor (TCR) diversity. This project will test the hypothesis that Tscm are efficacious for EBV-specific T-cell therapy. Clinical-grade enriched EBV-specific Tscm-CTLs will be prepared and used to treat patients with primary EBV lymphomas, diseases or post-transplant lymphoproliferative disease (PTLD) with limited other treatment options.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Patients' inclusion criteria:

Group A: Patients with EBV driven lymphomas (e.g., NK/T-cell lymphoma), with EBV complications (e.g. HLH, CAEBV) or patients with primary immunodeficiency disorders with high risk for EBV complications (e.g. SCID) with planned allogeneic HCT
Group B: EBV-driven PTLD that develop after a HCT or SOT

For both groups:

All age groups
Negative pregnancy test in female patients of childbearing potential.
Signed written informed consent of patient or/and parents

Patients' exclusion criteria:

Patients receiving anti-thymocyte globulin or Campath within 28 days of infusion
Patients with active, acute GvHD grades III-IV
Previous severe reaction to dimethylsulfoxide (DMSO)

Donors' inclusion criteria:

EBV positive serology (VCA and Epstein-Barr nuclear antigen (EBNA) immunoglobulin G (IgG) positive)
Detectable interferon (IFN)-y-secreting T cells (>100 SFC/10e6 PBMC) measured by Elispot to the EBV consensus peptide pool
Suitability for blood or HCT donation meeting requirements of local institutional guidelines
An informed consent for EBV Tscm CTL manufacturing
Age > 18 years

Donors' exclusion criteria:

Detectable IFN-y-secreting T-cells <100 spot-forming cell (SFC)/10e6 PBMC measured by Elispot to EBV select
Unwilling and/or unable to donate, according to the donor center

Treatment and study plan

Donor-derived ex-vivo expanded EBV Tscm CTL

Drug

Cryopreserved cells will be thawed and infused at three time points. Dosing will be 2x10e6 EBV CTLs per kg of body weight. No prior lymphodepletion will be performed.

Primary outcomes

Assessment of feasibility to expand Tscm-enriched EBV CTLs

Time frame: one time assessment on day 9-11 of expansion before cryopreservation (plus at least 7 days for microbiological culture)

Feasibility is defined as meeting the release criteria of EBV Tscm-CTL endproduct.

Release criteria for the EBV Tscm-CTL follow Swissmedic Investigational Medicinal Product Dossier (IMPD). This includes viability of cluster of differentiation 3 (CD3)+ >70%, absolute CD3 count per kg of body weight per dose (≤2x10e6/kg), and a purity of CD3+ >90%. These criteria will be assessed before cryopreservation. A negative culture for bacteria and fungi for at least 7 days, endotoxin testing ≤5 EU/ml and negative result for Mycoplasma is required.
Safety of EBV Tscm-CTL infusion assessed by number of early infusion-related events

Time frame: up to 12 hours after first dose of EBV Tscm-CTL infusion

Number of early infusion-related events (early infusion-related events are clinically significant alterations of vital signs)
Safety of EBV Tscm-CTL infusion assessed by number of late clinical reaction to EBV Tscm-CTLs

Time frame: from 12 hours after first dose until 3 months after the last dose of EBV CTLs

Late clinical reaction to EBV Tscm-CTLs are signs of acute graft-versus-host disease (GvHD). Acute GVHD will be graded according to the modified Glucksberg criteria.

Study contacts

Contact information is provided by the study sponsor or research team.

Nina Khanna, Prof. Dr. med.

CONTACT

[email protected]

+41 61 328 73 25

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Registry information

Official study title

Epstein-Barr Virus (EBV) -Specific T Memory Stem Cell (Tscm) Therapy to Treat EBV- Driven Lymphomas/ Diseases

Acronym: ESPECT

Important dates

Study start: 2026
Primary completion: 2031
Study completion: 2031
First posted: Jan 18, 2023
Registry last updated: Mar 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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