Clinical trial

Epstein-Barr Virus (EBV) -Specific T Memory Stem Cell (Tscm) Therapy to Treat EBV- Driven Lymphomas/ Diseases

Name

2022-01210; am22Khanna

Description

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.

Trial arms

Trial start

2024-11-01

Estimated PCD

2025-12-01

Trial end

2025-12-01

Status

Not yet recruiting

Phase

Early phase I

Treatment

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.

Arms:

Group A: patients who undergo allogeneic HCT, Group B: patients after HCT or SOT

Size

Primary endpoint

Assessment of feasibility to expand Tscm-enriched EBV CTLs

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

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

from 12 hours after first dose until 3 months after the last dose of EBV CTLs

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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Multi-center open-label, non-randomized phase I/II study.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 10, 'type': 'ESTIMATED'}}

Updated at

2024-02-20

1 organization

1 product

2 indications

Organization

University Hospital Basel

Product

Donor-derived ex-vivo expanded EBV Tscm CTL

Indication

Epstein-Barr Virus Lymphoma

Indication

Post-transplant Lymphoproliferative Disease