CCS: 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®

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Recruiting

CT.gov ID

NCT02007356

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Adenovirus Infection EBV Cytomegalovirus Infections Cytokine Capture System Allogenic Disease	Biological: IFN-γ positive selected T-cells	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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®

Actual Study Start Date :

Dec 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: allogeneic HSCT 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

Arm

Intervention/Treatment

Experimental: allogeneic HSCT

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

Outcome Measures

Primary Outcome Measures

Level of enriched IFN-γ+ T-cells [7 days]

Secondary Outcome Measures

Treatment efficacy [7 days]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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 -