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®

NCT ID: NCT02007356

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2026-12-31

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).

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

IFN-γ positive selected T-cells

Intervention Type: BIOLOGICAL

Interventions

IFN-γ positive selected T-cells

Intervention Type: BIOLOGICAL

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:

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 -

Exclusion Criteria

• graft-versus-host disease (GVHD) > grade 2 at the time point of planned infusion
• Known allergy to iron-dextran or murine antibodies

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nina Khanna, Dr.

Role: PRINCIPAL_INVESTIGATOR

Universitätsspital Basel, Klinik für Infektiologie

Locations

Universitätsspital Basel

Basel, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Nina Khanna, MD

Role: CONTACT

nina.khanna@usb.ch

+41-61-2652525 (Zentrale)

Facility Contacts

Nina Khanna, Dr.

Role: primary

nina.khanna@usb.ch

0041-61- ext. 7325

References

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.

Reference Type: BACKGROUND

PMID: 15134189 (View on PubMed)

Other Identifiers

EKBB 205/13; me12Khanna

Identifier Type: -

Identifier Source: org_study_id