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)

University Hospital Basel

Status and phase: Enrolling; Phase 2

Conditions: Allogenic Disease; EBV; Adenovirus Infection; Cytokine Capture System; Cytomegalovirus Infections

Treatments: Biological: IFN-γ positive selected T-cells

Study type: Interventional

Funder types: Other

Identifiers

NCT02007356

EKBB 205/13 me12Khanna;

Details and patient eligibility

About

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).

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

allogeneic HSCT

Experimental group

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.

Treatment:

Biological: IFN-γ positive selected T-cells