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Not yet recruiting NCT05688241

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

Phase I / Phase II Interventional EBV Lymphoma Post-transplant Lymphoproliferative Disease (PTLD)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Donor-derived ex-vivo expanded EBV Tscm CTL.
Who it may be relevant to
Registry conditions: EBV Lymphoma, Post-transplant Lymphoproliferative Disease (PTLD). Basic parameters: No limits · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Switzerland
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Detailed description

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.

Interventions

  • Drug Donor-derived ex-vivo expanded EBV Tscm CTL
    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 outcome measures

  • 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)]
  • 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]
  • 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]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

Switzerland · 8 centers
  • University Hospital Basel, Klinik für Infektiologie und Spitalhygiene — Basel
  • Universitäts-Kinderspital beider Basel (UKBB) — Basel
  • Universitätsspital Bern, Klinik für Infektiologie — Bern
  • Hôpitaux Universitaires de Genève, Hôpital des Enfants — Geneva
  • Hôpitaux Universitaires de Genève, Service d'Hématologie — Geneva
  • Centre hospitalier universitaire vaudois, Service et Laboratoire central d'hématologie — Lausanne
  • Kinderspital Zürich — Zurich
  • University Hospital Zurich, Hämatologie — Zurich

Identifiers

NCT: NCT05688241 · 2022-01210; am22Khanna

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗