Back to resultsA 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)
Primary Purpose
Adenovirus Infection, EBV, Cytomegalovirus Infections
Status
Recruiting
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
IFN-γ positive selected T-cells
Sponsored by
About this trial
This is an interventional treatment trial for Adenovirus Infection
Eligibility 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:
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
Sites / Locations
- Universitätsspital BaselRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
allogeneic HSCT
Arm Description
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.
Outcomes
Primary Outcome Measures
Level of enriched IFN-γ+ T-cells
Secondary Outcome Measures
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
Full Information
NCT ID
NCT02007356
First Posted
November 26, 2013
Last Updated
April 11, 2022
Sponsor
University Hospital, Basel, Switzerland
1. Study Identification
Unique Protocol Identification Number
NCT02007356
Brief Title
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®
Acronym
CCS
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®
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 2014 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland
4. Oversight
Data Monitoring Committee
Yes
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenovirus Infection, EBV, Cytomegalovirus Infections, Cytokine Capture System, Allogenic Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
allogeneic HSCT
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
IFN-γ positive selected T-cells
Primary Outcome Measure Information:
Title
Level of enriched IFN-γ+ T-cells
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Treatment efficacy
Description
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
Time Frame
7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nina Khanna, MD
Phone
+41-61-2652525 (Zentrale)
Email
nina.khanna@usb.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nina Khanna, Dr.
Organizational Affiliation
Universitätsspital Basel, Klinik für Infektiologie
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitätsspital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nina Khanna, Dr.
Phone
0041-61-
Ext
7325
Email
nina.khanna@usb.ch
First Name & Middle Initial & Last Name & Degree
Nina Khanna, Dr.
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
15134189
Citation
Kaufmann GR, Khanna N, Weber R, Perrin L, Furrer H, Cavassini M, Ledergerber B, Vernazza P, Bernasconi E, Rickenbach M, Hirschel B, Battegay M; Swiss HIV Cohort Study. Long-term virological response to multiple sequential regimens of highly active antiretroviral therapy for HIV infection. Antivir Ther. 2004 Apr;9(2):263-74.
Results Reference
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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®
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