Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Donor-derived ex-vivo expanded EBV Tscm CTL | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| 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 |
| 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 |
Not provided
Not provided
Patients' inclusion criteria:
For both groups:
Patients' exclusion criteria:
Donors' inclusion criteria:
Donors' exclusion criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nina Khanna, Prof. Dr. med. | Contact | +41 61 328 73 25 | nina.khanna@usb.ch |
| Name | Affiliation | Role |
|---|---|---|
| Nina Khanna, Prof. Dr. med. | Klinik für Infektiologie und Spitalhygiene, University Hospital of Basel | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel, Klinik für Infektiologie und Spitalhygiene | Basel | 4031 | Switzerland |
Not provided
Multi-center open-label, non-randomized phase I/II study.
Not provided
Not provided
Not provided
Not provided
| Universitäts-Kinderspital beider Basel (UKBB) | Basel | 4056 | Switzerland |
|
| Universitätsspital Bern, Klinik für Infektiologie | Bern | 3010 | Switzerland |
|
| Hôpitaux Universitaires de Genève, Hôpital des Enfants | Geneva | 1205 | Switzerland |
|
| Hôpitaux Universitaires de Genève, Service d'Hématologie | Geneva | 1211 | Switzerland |
|
| Centre hospitalier universitaire vaudois, Service et Laboratoire central d'hématologie | Lausanne | 1011 | Switzerland |
|
| Kinderspital Zürich | Zurich | 8032 | Switzerland |
|
| University Hospital Zurich, Hämatologie | Zurich | 8091 | Switzerland |
|
| ID | Term |
|---|---|
| D020031 | Epstein-Barr Virus Infections |
| ID | Term |
|---|---|
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
Not provided
Not provided