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

NCT ID: NCT05688241

Last Updated: 2025-03-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-11-30
• Study Completion Date: 2031-12-31

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.

Conditions

EBV Lymphoma; Post-transplant Lymphoproliferative Disease (PTLD)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A: patients who undergo allogeneic HCT

Patients with EBV driven lymphomas (e.g., natural killer (NK)/T-cell lymphoma), with EBV complications (e.g. haemophagocytic lymphohistiocytosis (HLH), CAEBV) or patients with primary immunodeficiency disorders with high risk for EBV complications (e.g. SCID) with planned allogeneic HCT.

Group Type: EXPERIMENTAL

Donor-derived ex-vivo expanded EBV Tscm CTL

Intervention Type: 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.

Group B: patients after HCT or SOT

EBV-driven PTLD that develop after a HCT or solid organ transplantation (SOT) and show decreased response to rituximab.

Group Type: EXPERIMENTAL

Donor-derived ex-vivo expanded EBV Tscm CTL

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• 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

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)

• 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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nina Khanna, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Klinik für Infektiologie und Spitalhygiene, University Hospital of Basel

Locations

University Hospital Basel, Klinik für Infektiologie und Spitalhygiene

Basel, , Switzerland

Universitäts-Kinderspital beider Basel (UKBB)

Basel, , Switzerland

Universitätsspital Bern, Klinik für Infektiologie

Bern, , Switzerland

Hôpitaux Universitaires de Genève, Hôpital des Enfants

Geneva, , Switzerland

Hôpitaux Universitaires de Genève, Service d'Hématologie

Geneva, , Switzerland

Centre hospitalier universitaire vaudois, Service et Laboratoire central d'hématologie

Lausanne, , Switzerland

Kinderspital Zürich

Zurich, , Switzerland

University Hospital Zurich, Hämatologie

Zurich, , Switzerland

Countries

Switzerland

Central Contacts

Nina Khanna, Prof. Dr. med.

Role: CONTACT

nina.khanna@usb.ch

+41 61 328 73 25

Facility Contacts

Nina Khanna, Prof. Dr. med.

Role: primary

nina.khanna@usb.ch

+41 61 328 73 25

Tamara Diesch- Furlanetto, Dr. med.

Role: primary

Urban Novak, Prof. Dr. med.

Role: primary

Marc Ansari, Prof. Dr. med.

Role: primary

Yves Chalandon, Prof. Dr. med.

Role: primary

Michel Duchosal, Prof. Dr. med.

Role: primary

Tayfun Güngör, Prof. Dr. med.

Role: primary

Dominik Schneidawind, PD Dr. med.

Role: primary

Other Identifiers

2022-01210; am22Khanna

Identifier Type: -

Identifier Source: org_study_id