A Study to Assess Safety and Feasibility of Direct Infusions of Donor-derived Virus-specific T-cells in Recipients of Hematopoietic Stem Cell Transplantation With Post-transplant Viral Infections Using the Cytokine Capture System®

Study Overview
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Brief Summary
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To assess the feasibility of donor-derived interferon (IFN)-γ positive select-ed virus-specific T-cells using the cytokine capture system® (CCS) and the safety of subsequent infusion in recipients of hematopoietic stem cell transplantation (HSCT) with treatment refractory post-transplant viral infections. The CCS has already been successfully used in clinical studies in Germany and United Kingdom (UK).

Official Title
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A Phase I/II Single-center Study to Assess Safety and Feasibility of Direct Infusions of Donor-derived Virus-specific T-cells in Recipients of Hematopoietic Stem Cell Transplantation With Post-transplant Viral Infections Using the Cytokine Capture System®

Conditions
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Adenovirus Infection, EBV, Cytomegalovirus Infections, Cytokine Capture System, Allogenic Disease

Intervention / Treatment
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* Biological: IFN-γ positive selected T-cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults > 18 years of age Undergone allogeneic HSCT Written informed consent Patients with treatment refractory infections with adenovirus, cytomegalovirus (CMV) or Epstein-Barr virus (EBV) will be included in case of fulfilling following criteria: Patient with Adenovirus Infection: Antiviral treatment with cidofovir for at least 7 days no virus load decrease ( ≤ 1 log) or virus load increase on treatment for at least 7 days or cluster of differentiation 3 (CD3) + cells < 300/µL on treatment for at least 7 days Or if antiviral treatment is contraindicated Patient with EBV: 1. After receipt of at least one anti-cluster of differentiation 20 antigen (CD20)-antibody treat-ment (375 mg/m2) No Virus load decrease (≤ 1 log) or virus load increase 7 days after receipt of treatment or CD3+ cells < 300/µL 7 days after receipt of treatment or Clinical progression Patient with CMV: Antiviral treatment with ganciclovir or foscavir for 14 days - No Virus load decrease (≤ 1 log) or virus load increase on day 14 Or if > 2 recurrences despite antiviral treatment with ganciclovir or foscavir for 14 days and CD3+ cells < 300/µL Or if antiviral treatment is contraindicated - Patient Exclusion Criteria: graft-versus-host disease (GVHD) > grade 2 at the time point of planned infusion Known allergy to iron-dextran or murine antibodies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: allogeneic HSCT<br>The present study will evaluate and validate in a single-center, open-label, single arm fashion the safety and feasibility of direct infusions of donor-derived pathogen-specific IFN-γ positive T-cells in recipients of HSCT with post-transplant viral infection according to the previously clinically certified CCS® [3-6]. The Investigator will first generate and apply IFN-γ positive selected T-cells to recipients of HSCT with CMV, EBV or adenovirus as previously published. The Investigator aim is to include 6 patients from the University Hospital of Basel. With confirmed safety the investigator will in the future perform an efficacy study and extend this treat-ment for other clinically relevant pathogens including human herpesvirus (HHV)-6, HHV-8, polyomaviruses JC and BK and fungi including Aspergillus fumigatus and Candida albicans, to other immunosuppressed patients such as solid organ transplant (SOT) recipients. | Biological: IFN-γ positive selected T-cells<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of enriched IFN-γ+ T-cells |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment efficacy | Treatment efficacy defined as reduction of virus load, in vivo expansion of antigen-specific T cells in peripheral blood as well as reduction of clinical signs of specific viral infection | 7 days |