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

Post-transplant Lymphoproliferative Disease (PTLD) Clinical Trial

— ESPECT  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05688241
• Other study ID #: 2022-01210; am22Khanna
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: November 2024
• Est. completion date: December 2025

Study information

• Verified date: February 2024
• Source: University Hospital, Basel, Switzerland
• Contact: Nina Khanna, Prof. Dr. med.
• Phone: +41 61 328 73 25
• Email: nina.khanna[@]usb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoproliferative Disorders
• Post-transplant Lymphoproliferative Disease (PTLD)

Intervention

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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of feasibility to expand Tscm-enriched EBV CTLs	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.	one time assessment on day 9-11 of expansion before cryopreservation (plus at least 7 days for microbiological culture)
Primary	Safety of EBV Tscm-CTL infusion assessed by number of early infusion-related events	Number of early infusion-related events (early infusion-related events are clinically significant alterations of vital signs)	up to 12 hours after first dose of EBV Tscm-CTL infusion
Primary	Safety of EBV Tscm-CTL infusion assessed by number of late clinical reaction to EBV Tscm-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.	from 12 hours after first dose until 3 months after the last dose of EBV CTLs