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

Primary Purpose

EBV Lymphoma, Post-transplant Lymphoproliferative Disease (PTLD)

Status
Not yet recruiting
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Donor-derived ex-vivo expanded EBV Tscm CTL
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for EBV Lymphoma focused on measuring 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)

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A: patients who undergo allogeneic HCT

Group B: patients after HCT or SOT

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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.
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)
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.

Secondary Outcome Measures

Full Information

First Posted
December 21, 2022
Last Updated
July 25, 2023
Sponsor
University Hospital, Basel, Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT05688241
Brief Title
EBV-Tscm Cytotoxic T Cells (CTLs) for EBV- Driven Lymphomas/ Diseases
Acronym
ESPECT
Official Title
Epstein-Barr Virus (EBV) -Specific T Memory Stem Cell (Tscm) Therapy to Treat EBV- Driven Lymphomas/ Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Multi-center open-label, non-randomized phase I/II study.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A: patients who undergo allogeneic HCT
Arm Type
Experimental
Arm Description
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.
Arm Title
Group B: patients after HCT or SOT
Arm Type
Experimental
Arm Description
EBV-driven PTLD that develop after a HCT or solid organ transplantation (SOT) and show decreased response to rituximab.
Intervention Type
Drug
Intervention Name(s)
Donor-derived ex-vivo expanded EBV Tscm CTL
Intervention Description
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 Measure Information:
Title
Assessment of feasibility to expand Tscm-enriched EBV CTLs
Description
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.
Time Frame
one time assessment on day 9-11 of expansion before cryopreservation (plus at least 7 days for microbiological culture)
Title
Safety of EBV Tscm-CTL infusion assessed by number of early infusion-related events
Description
Number of early infusion-related events (early infusion-related events are clinically significant alterations of vital signs)
Time Frame
up to 12 hours after first dose of EBV Tscm-CTL infusion
Title
Safety of EBV Tscm-CTL infusion assessed by number of late clinical reaction to EBV Tscm-CTLs
Description
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.
Time Frame
from 12 hours after first dose until 3 months after the last dose of EBV CTLs

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nina Khanna, Prof. Dr. med.
Phone
+41 61 328 73 25
Email
nina.khanna@usb.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nina Khanna, Prof. Dr. med.
Organizational Affiliation
Klinik für Infektiologie und Spitalhygiene, University Hospital of Basel
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Basel, Klinik für Infektiologie und Spitalhygiene
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nina Khanna, Prof. Dr. med.
Phone
+41 61 328 73 25
Email
nina.khanna@usb.ch
First Name & Middle Initial & Last Name & Degree
Nina Khanna, Prof. Dr. med.
First Name & Middle Initial & Last Name & Degree
Andreas Holbro, Prof. Dr. med.
Facility Name
Universitäts-Kinderspital beider Basel (UKBB)
City
Basel
ZIP/Postal Code
4056
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tamara Diesch- Furlanetto, Dr. med.
First Name & Middle Initial & Last Name & Degree
Tamara Diesch- Furlanetto, Dr. med.
Facility Name
Universitätsspital Bern, Klinik für Infektiologie
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Urban Novak, Prof. Dr. med.
First Name & Middle Initial & Last Name & Degree
Urban Novak, Prof. Dr. med.
Facility Name
Hôpitaux Universitaires de Genève, Hôpital des Enfants
City
Genève
ZIP/Postal Code
1205
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc Ansari, Prof. Dr. med.
First Name & Middle Initial & Last Name & Degree
Marc Ansari, Prof. Dr. med.
Facility Name
Hôpitaux Universitaires de Genève, Service d'Hématologie
City
Genève
ZIP/Postal Code
1211
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yves Chalandon, Prof. Dr. med.
First Name & Middle Initial & Last Name & Degree
Yves Chalandon, Prof. Dr. med.
Facility Name
Centre hospitalier universitaire vaudois, Service et Laboratoire central d'hématologie
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michel Duchosal, Prof. Dr. med.
First Name & Middle Initial & Last Name & Degree
Michel Duchosal, Prof. Dr. med.
Facility Name
Kinderspital Zürich
City
Zürich
ZIP/Postal Code
8032
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tayfun Güngör, Prof. Dr. med.
First Name & Middle Initial & Last Name & Degree
Tayfun Güngör, Prof. Dr. med.
Facility Name
University Hospital Zurich, Hämatologie
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominik Schneidawind, PD Dr. med.
First Name & Middle Initial & Last Name & Degree
Nathan Wolfensberger, Dr. med.
First Name & Middle Initial & Last Name & Degree
Dominik Schneidawind, PD Dr. med.

12. IPD Sharing Statement

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

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