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

University Hospital Basel

Status and phase: Begins enrollment in 8 months; Phase 2; Phase 1

Conditions: EBV Lymphoma; Post-transplant Lymphoproliferative Disease (PTLD)

Treatments: Drug: Donor-derived ex-vivo expanded EBV Tscm CTL

Study type: Interventional

Funder types: Other

Identifiers

NCT05688241

2022-01210 am22Khanna;

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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10 participants in 2 patient groups

Group A: patients who undergo allogeneic HCT

Experimental group

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.

Treatment:

Drug: Donor-derived ex-vivo expanded EBV Tscm CTL

Group B: patients after HCT or SOT

Experimental group

Description:

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

Treatment:

Drug: Donor-derived ex-vivo expanded EBV Tscm CTL