Preventative/Preemptive Adoptive Transfer of Peptide Stimulated CMV/EBV Specific T-cells in Patients After Allogeneic Stem Cell Transplantation

Phase 1

Completed

• Conditions: Patients Undergoing Allogeneic Stem Cell Transplantation
• Interventions: Biological: CMV/EBV specific T-cell

• Registration Number: NCT02227641
• Lead Sponsor: University of Erlangen-Nürnberg Medical School

Brief Summary

In patients after allogeneic stem cell transplantation reactivation of latent herpesviruses such as Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) is a frequent and life threatening complication requiring antiviral treatment. The underlying problem is a severe suppression of the donors immune system after transplantation into the patient. Herpesviruses such as CMV and EBV persist after primary infection life long in the host and therefore require constant immunological control. This control is largely provided by the T-cell compartment of the immune system. After allogeneic stem cell transplantation the T-cell compartment requires a long time for its reconstitution since only a small fraction of the donor T-cells are transplanted. During this time Herpesviruses can reoccur due to the lack of effective T-cell control.

This study therefore aims at reconstituting the T-cell compartment with CMV and EBV specific T-cells at an early time point after allogeneic stem cell transplantation. It is mainly a phase I study to demonstrate that these in vitro generated T-cells can be applied safely in this patient population. The study also aims at demonstrating the efficacy of CMV/EBV specific T-cells by monitoring viral reactivation and use of antiviral drugs. The hypothesis is, that CMV/EBV specific T-cell can be applied safely and do not result in graft versus host disease and that they successfully prevent reactivation of CMV and EBV after adoptive transfer in patients after allogeneic stem cell transplantation.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-08-26
• Study First Submitted QC: 2014-08-27
• Study First Posted: 2014-08-28
• Study Start: 2014-10
• Primary Completion: 2016-10
• Study Completion: 2017-03
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-10
• Last Update Posted: 2020-12-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Indication for allogeneic stem cell transplantation
• HLA identical donor, related or unrelated, 10/10 match
• Stem cell source: G-SCF mobilized peripheral blood stem cells
• Presence of at least one HLA allele: A0101, A0201, B0702, B0801, B3501, C0702
• Positive EBV serology of the donor
• Positive CMV serology of the donor
• Adequate contraception

Exclusion Criteria

• Donor CMV seronegative
• Donor EBV seronegative
• Stem cell source: bone marrow or cord blood
• Alemtuzumab for conditioning
• Sorror Score >3
• Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Adoptive transfer of CMV/EBV specific T-cells	CMV/EBV specific T-cell	Repetitive adoptive T-cell transfer starting at day 30 after allogeneic stem cell transplantation.

Primary Outcome Measures

Name	Time	Method
Toxicity of adoptive transfer of CMV/EBV specific T-cells	1-28 days after adoptive T-cell transfer	Assessment of acute transfusion toxicity within 24 hours after adoptive T-cell transfer.; Assessment of the development of acute transfusion associated acute graft versus host disease (GvHD) within 28 days after adoptive T-cell transfer

Secondary Outcome Measures

Name	Time	Method
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on virus reactivation	During observation period until day 204 post transplantation	Incidence of reactivation of CMV and/or EBV during the observation period assessed by virus specific PCR of peripheral blood.
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of antiviral therapy	During observation period until day 204 post transplantation	Cumulative dose of Ganciclovir, Valganciclovir, Foscarnet, Cidofovir
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of Rituximab	During observation period until day 204 post transplantation	Cumulative dose of Rituximab.
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on T-cell reconstitution	During observation period until day 204 post transplantation	Immunomonitoring of peripheral blood by flow cytometry.

Trial Locations

Locations (6)

Universitiy Hospital Erlangen; 🇩🇪 Erlangen, Germany

Medical Center Augsburg; 🇩🇪 Augsburg, Germany

Charité University Hospital Berlin; 🇩🇪 Berlin, Germany

University of Mainz; 🇩🇪 Mainz, Germany

University of Regensburg; 🇩🇪 Regensburg, Germany

University of Munich LMU; 🇩🇪 Munich, Germany