Clinical trial NCT05688241: EBV-Tscm Cytotoxic T Cells (CTLs) for EBV- Driven Lymphomas/ Diseases
Official title: Epstein-Barr Virus (EBV) -Specific T Memory Stem Cell (Tscm) Therapy to Treat EBV- Driven Lymphomas/ Diseases
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: EBV Lymphoma
Post-transplant Lymphoproliferative Disease (PTLD)
Keywords: EBV-driven Lymphomas
EBV disease
Epstein-Barr Virus (EBV)
Memory Stem Cell Therapy
Epstein-Barr Virus-specific T Memory Stem Cell Therapy (EBV-Tscm)
cytotoxic T-cell line (CTL)
T memory stem cells (Tscm)
T-cell receptor (TCR)
post-transplant lymphoproliferative disease (PTLD)
Wnt-β-catenin inhibition
hematopoietic cell transplantation (HCT)
Hematopoietic stem cell transplantation (HSCT)
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2023-01-18
Enrollment: 10
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center open-label, non-randomized phase I/II study.
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Assessment of feasibility to expand Tscm-enriched EBV CTLs
timeFrame: one time assessment on day 9-11 of expansion before cryopreservation (plus at least 7 days for microbiological culture)
measure: Safety of EBV Tscm-CTL infusion assessed by number of early infusion-related events
timeFrame: up to 12 hours after first dose of EBV Tscm-CTL infusion
measure: Safety of EBV Tscm-CTL infusion assessed by number of late clinical reaction to EBV Tscm-CTLs
timeFrame: from 12 hours after first dose until 3 months after the last dose of EBV CTLs
Secondary outcomes:
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Klinik für Infektiologie und Spitalhygiene
city: Basel
country: Switzerland
facility: Universitäts-Kinderspital beider Basel (UKBB)
city: Bern
country: Switzerland
facility: Universitätsspital Bern, Klinik für Infektiologie
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève, Hôpital des Enfants
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève, Service d'Hématologie
city: Lausanne
country: Switzerland
facility: Centre hospitalier universitaire vaudois, Service et Laboratoire central d'hématologie
city: Zürich
country: Switzerland
facility: Kinderspital Zürich
city: Zürich
country: Switzerland
facility: University Hospital Zurich, Hämatologie
Study officials:
affiliation: Klinik für Infektiologie und Spitalhygiene, University Hospital of Basel
name: Nina Khanna, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: