EBV LymphomaPhase 1/2ESPECTNCT05688241
EBV-Tscm Cytotoxic T Cells (CTLs) for EBV- Driven Lymphomas/ Diseases
A Phase 1/2 study testing Donor-derived ex-vivo expanded EBV Tscm CTL in people with EBV Lymphoma and Post-transplant Lymphoproliferative Disease (PTLD), run by University Hospital, Basel, Switzerland at 8 sites in Switzerland.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- EBV Lymphoma, Post-transplant Lymphoproliferative Disease (PTLD)
- What is being tested?
- Donor-derived ex-vivo expanded EBV Tscm CTL
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 8 sitesSwitzerland
- Study dates
- Nov 2026to Dec 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Switzerland8 sites
University Hospital Basel, Klinik für Infektiologie und Spitalhygiene
Basel, 4031
Nina Khanna, Prof. Dr. med., +41 61 328 73 25, nina.khanna@usb.ch
Nina Khanna, Prof. Dr. med.
Universitäts-Kinderspital beider Basel (UKBB)
Basel, 4056
Tamara Diesch- Furlanetto, Dr. med.
Tamara Diesch- Furlanetto, Dr. med.
Universitätsspital Bern, Klinik für Infektiologie
Bern, 3010
Urban Novak, Prof. Dr. med.
Urban Novak, Prof. Dr. med.
Hôpitaux Universitaires de Genève, Hôpital des Enfants
Geneva, 1205
Marc Ansari, Prof. Dr. med.
Marc Ansari, Prof. Dr. med.
Hôpitaux Universitaires de Genève, Service d'Hématologie
Geneva, 1211
Yves Chalandon, Prof. Dr. med.
Yves Chalandon, Prof. Dr. med.
Centre hospitalier universitaire vaudois, Service et Laboratoire central d'hématologie
Lausanne, 1011
Michel Duchosal, Prof. Dr. med.
Michel Duchosal, Prof. Dr. med.
Kinderspital Zürich
Zurich, 8032
Tayfun Güngör, Prof. Dr. med.
Tayfun Güngör, Prof. Dr. med.
University Hospital Zurich, Hämatologie
Zurich, 8091
Dominik Schneidawind, PD Dr. med.
Nathan Wolfensberger, Dr. med.
About this study
Official title: 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.
Read the 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.
- Being tested
- Donor-derived ex-vivo expanded EBV Tscm CTL
- 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)
- Medical subject headings
- Epstein-Barr Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donor-derived ex-vivo expanded EBV Tscm CTLDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Group A: patients who undergo allogeneic HCT | Experimental | 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. Receives: Drug: Donor-derived ex-vivo expanded EBV Tscm CTL |
| Group B: patients after HCT or SOT | Experimental | EBV-driven PTLD that develop after a HCT or solid organ transplantation (SOT) and show decreased response to rituximab. Receives: Drug: Donor-derived ex-vivo expanded EBV Tscm CTL |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: one time assessment on day 9-11 of expansion before cryopreservation (plus at least 7 days for microbiological culture)
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)
Measured: 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
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.
Measured: from 12 hours after first dose until 3 months after the last dose of EBV CTLs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2023
- Study startNov 2026 (estimated)
- Primary completionDec 2031 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EBV LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Multi-center open-label, non-randomized phase I/II study.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nina Khanna, Prof. Dr. med., Principal investigator, Klinik für Infektiologie und Spitalhygiene, University Hospital of Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05688241
- Sponsor's protocol ID
- 2022-01210; am22Khanna
- Acronym
- ESPECT
- Status last verified
- Feb 2025
- First submitted
- 21 Dec 2022
- Last updated
- 3 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epstein-Barr Virus (EBV) -Specific T Memory Stem Cell (Tscm) Therapy to Treat EBV- Driven Lymphomas/ Diseases
- ClinicalTrials.gov ID
- NCT05688241
- Acronym / sponsor ID
- ESPECT / 2022-01210; am22Khanna
- 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)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Nov 2026 (estimated)
- Primary completion
- Dec 2031 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 18 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multi-center open-label, non-randomized phase I/II study.
| Arm | Type | Receives |
|---|---|---|
| Group A: patients who undergo allogeneic HCT | Experimental | Drug: Donor-derived ex-vivo expanded EBV Tscm CTLPatients 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 B: patients after HCT or SOT | Experimental | Drug: Donor-derived ex-vivo expanded EBV Tscm CTLEBV-driven PTLD that develop after a HCT or solid organ transplantation (SOT) and show decreased response to rituximab. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Donor-derived ex-vivo expanded EBV Tscm CTLCryopreserved 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. | Drug | Group A: patients who undergo allogeneic HCT, Group B: patients after HCT or SOT |
Primary outcome
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.
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)
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nina Khanna, Prof. Dr. med. principal investigator
Klinik für Infektiologie und Spitalhygiene, University Hospital of Basel
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Donor-derived ex-vivo expanded EBV Tscm CTL in people with EBV Lymphoma and Post-transplant Lymphoproliferative Disease (PTLD), run by University Hospital, Basel, Switzerland at 8 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nina Khanna, Prof. Dr. med. (+41 61 328 73 25, nina.khanna@usb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2025; AzTrials last refreshed its copy on 26 Oct 2026.