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® (CCS)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2013 by University Hospital, Basel, Switzerland
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT02007356
First received: November 26, 2013
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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®

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Level of enriched IFN-γ+ T-cells [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Treatment efficacy [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 6
Study Start Date: April 2014
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 SOT recipients.

Biological: IFN-γ positive selected T-cells

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

  1. 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
  2. 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:

  1. Antiviral treatment with ganciclovir or foscavir for 14 days

    - No Virus load decrease (≤ 1 log) or virus load increase on day 14

  2. Or if > 2 recurrences despite antiviral treatment with ganciclovir or foscavir for 14 days and CD3+ cells < 300/µL
  3. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02007356

Contacts
Contact: Nina Khanna, MD +41-61-2652525 (Zentrale) nina.khanna@usb.ch

Locations
Switzerland
Universitätsspital Basel Not yet recruiting
Basel, Switzerland, 4031
Contact: Nina Khanna, Dr.    0041-61- ext 7325    nina.khanna@usb.ch   
Principal Investigator: Nina Khanna, Dr.         
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Nina Khanna, Dr. Universitätsspital Basel,Klinik für Infektiologie und Spitalhygiene, Petersgraben 4, Switzerland 4031
  More Information

Publications:
Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT02007356     History of Changes
Other Study ID Numbers: EKBB 205/13
Study First Received: November 26, 2013
Last Updated: December 9, 2013
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Adenoviridae Infections
Cytomegalovirus Infections
Virus Diseases
DNA Virus Infections
Herpesviridae Infections

ClinicalTrials.gov processed this record on July 22, 2014