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

February 19, 2024 updated by: University Hospital, Basel, Switzerland

Epstein-Barr Virus (EBV) -Specific T Memory Stem Cell (Tscm) Therapy to Treat 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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Nina Khanna, Prof. Dr. med.
  • Phone Number: +41 61 328 73 25
  • Email: nina.khanna@usb.ch

Study Locations

  • Switzerland
      • Basel, Switzerland, 4031
        • University Hospital Basel, Klinik für Infektiologie und Spitalhygiene
        • Contact:
        • Principal Investigator:
          • Nina Khanna, Prof. Dr. med.
        • Sub-Investigator:
          • Andreas Holbro, Prof. Dr. med.
      • Basel, Switzerland, 4056
        • Universitäts-Kinderspital beider Basel (UKBB)
        • Contact:
          • Tamara Diesch- Furlanetto, Dr. med.
        • Principal Investigator:
          • Tamara Diesch- Furlanetto, Dr. med.
      • Bern, Switzerland, 3010
        • Universitätsspital Bern, Klinik für Infektiologie
        • Contact:
          • Urban Novak, Prof. Dr. med.
        • Principal Investigator:
          • Urban Novak, Prof. Dr. med.
      • Genève, Switzerland, 1205
        • Hôpitaux Universitaires de Genève, Hôpital des Enfants
        • Contact:
          • Marc Ansari, Prof. Dr. med.
        • Principal Investigator:
          • Marc Ansari, Prof. Dr. med.
      • Genève, Switzerland, 1211
        • Hôpitaux Universitaires de Genève, Service d'Hématologie
        • Contact:
          • Yves Chalandon, Prof. Dr. med.
        • Principal Investigator:
          • Yves Chalandon, Prof. Dr. med.
      • Lausanne, Switzerland, 1011
        • Centre hospitalier universitaire vaudois, Service et Laboratoire central d'hématologie
        • Contact:
          • Michel Duchosal, Prof. Dr. med.
        • Principal Investigator:
          • Michel Duchosal, Prof. Dr. med.
      • Zürich, Switzerland, 8032
        • Kinderspital Zürich
        • Contact:
          • Tayfun Güngör, Prof. Dr. med.
        • Principal Investigator:
          • Tayfun Güngör, Prof. Dr. med.
      • Zürich, Switzerland, 8091
        • University Hospital Zurich, Hämatologie
        • Contact:
          • Dominik Schneidawind, PD Dr. med.
        • Principal Investigator:
          • Nathan Wolfensberger, Dr. med.
        • Principal Investigator:
          • Dominik Schneidawind, PD Dr. med.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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.
Experimental: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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
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
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.
one time assessment on day 9-11 of expansion before cryopreservation (plus at least 7 days for microbiological culture)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Basel, Switzerland

Investigators

  • Principal Investigator: Nina Khanna, Prof. Dr. med., Klinik für Infektiologie und Spitalhygiene, University Hospital of Basel

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 1, 2024

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

December 21, 2022

First Submitted That Met QC Criteria

January 13, 2023

First Posted (Actual)

January 18, 2023

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

February 19, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-01210; am22Khanna

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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