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JOURNAL ONKOLOGIE – STUDIE
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EBV-Tscm Cytotoxic T Cells (CTLs) for EBV- Driven Lymphomas/ Diseases

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NCT-Nummer:
NCT05688241

Studienbeginn:
November 2024

Letztes Update:
20.02.2024

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

Indikation (Clinical Trials):
Lymphoma, Lymphoproliferative Disorders

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
-

Sponsor:
University Hospital, Basel, Switzerland

Collaborator:
-

Studienleiter

Nina Khanna, Prof. Dr. med.
Principal Investigator
Klinik für Infektiologie und Spitalhygiene, University Hospital of Basel

Kontakt

Studienlocations
(3 von 8)

University Hospital Basel, Klinik für Infektiologie und Spitalhygiene
4031 Basel
Switzerland» Google-Maps
Ansprechpartner:
Nina Khanna, Prof. Dr. med.
Phone: +41 61 328 73 25
E-Mail: nina.khanna@usb.ch» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. 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.

2. 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)

3. 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.

Studien-Arme

  • Experimental: Group A: patients who undergo allogeneic HCT
    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.
  • Experimental: Group B: patients after HCT or SOT
    EBV-driven PTLD that develop after a HCT or solid organ transplantation (SOT) and show decreased response to rituximab.

Geprüfte Regime

  • 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.

Quelle: ClinicalTrials.gov


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