Trial Title:
EBV-Tscm Cytotoxic T Cells (CTLs) for EBV- Driven Lymphomas/ Diseases
NCT ID:
NCT05688241
Condition:
EBV Lymphoma
Post-transplant Lymphoproliferative Disease (PTLD)
Conditions: Official terms:
Lymphoma
Lymphoproliferative Disorders
Conditions: 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)
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Multi-center open-label, non-randomized phase I/II study.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Donor-derived ex-vivo expanded EBV Tscm CTL
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.
Arm group label:
Group A: patients who undergo allogeneic HCT
Arm group label:
Group B: patients after HCT or SOT
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.
Criteria for 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
Gender:
All
Minimum age:
N/A
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospital Basel, Klinik für Infektiologie und Spitalhygiene
Address:
City:
Basel
Zip:
4031
Country:
Switzerland
Contact:
Last name:
Nina Khanna, Prof. Dr. med.
Phone:
+41 61 328 73 25
Email:
nina.khanna@usb.ch
Investigator:
Last name:
Nina Khanna, Prof. Dr. med.
Email:
Principal Investigator
Investigator:
Last name:
Andreas Holbro, Prof. Dr. med.
Email:
Sub-Investigator
Facility:
Name:
Universitäts-Kinderspital beider Basel (UKBB)
Address:
City:
Basel
Zip:
4056
Country:
Switzerland
Contact:
Last name:
Tamara Diesch- Furlanetto, Dr. med.
Investigator:
Last name:
Tamara Diesch- Furlanetto, Dr. med.
Email:
Principal Investigator
Facility:
Name:
Universitätsspital Bern, Klinik für Infektiologie
Address:
City:
Bern
Zip:
3010
Country:
Switzerland
Contact:
Last name:
Urban Novak, Prof. Dr. med.
Investigator:
Last name:
Urban Novak, Prof. Dr. med.
Email:
Principal Investigator
Facility:
Name:
Hôpitaux Universitaires de Genève, Hôpital des Enfants
Address:
City:
Genève
Zip:
1205
Country:
Switzerland
Contact:
Last name:
Marc Ansari, Prof. Dr. med.
Investigator:
Last name:
Marc Ansari, Prof. Dr. med.
Email:
Principal Investigator
Facility:
Name:
Hôpitaux Universitaires de Genève, Service d'Hématologie
Address:
City:
Genève
Zip:
1211
Country:
Switzerland
Contact:
Last name:
Yves Chalandon, Prof. Dr. med.
Investigator:
Last name:
Yves Chalandon, Prof. Dr. med.
Email:
Principal Investigator
Facility:
Name:
Centre hospitalier universitaire vaudois, Service et Laboratoire central d'hématologie
Address:
City:
Lausanne
Zip:
1011
Country:
Switzerland
Contact:
Last name:
Michel Duchosal, Prof. Dr. med.
Investigator:
Last name:
Michel Duchosal, Prof. Dr. med.
Email:
Principal Investigator
Facility:
Name:
Kinderspital Zürich
Address:
City:
Zürich
Zip:
8032
Country:
Switzerland
Contact:
Last name:
Tayfun Güngör, Prof. Dr. med.
Investigator:
Last name:
Tayfun Güngör, Prof. Dr. med.
Email:
Principal Investigator
Facility:
Name:
University Hospital Zurich, Hämatologie
Address:
City:
Zürich
Zip:
8091
Country:
Switzerland
Contact:
Last name:
Dominik Schneidawind, PD Dr. med.
Investigator:
Last name:
Nathan Wolfensberger, Dr. med.
Email:
Principal Investigator
Investigator:
Last name:
Dominik Schneidawind, PD Dr. med.
Email:
Principal Investigator
Start date:
November 2024
Completion date:
December 2025
Lead sponsor:
Agency:
University Hospital, Basel, Switzerland
Agency class:
Other
Source:
University Hospital, Basel, Switzerland
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05688241
