Clinical trial NCT02227641: Preventative/Preemptive Adoptive Transfer of Peptide Stimulated CMV/EBV Specific T-cells in Patients After Allogeneic Stem Cell Transplantation
Official title: Prospective, Open, Randomized, Two-arm, Controlled, Multicenter Clinical Phase I/IIa Trial to Evaluate the Safety and Efficacy of Adoptive Immunotherapy With Allogeneic CMV/EBV Specific, Peptide Stimulated T-cells (CD3+) for Prevention or Preemptive Therapy of Reactivation of CMV and/or EBV in Patients After Allogeneic, HLA Identical Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Patients Undergoing Allogeneic Stem Cell Transplantation
Keywords: CMV
Cytomegalovirus
EBV
Epstein Barr Virus
virus
T cell
adoptive transfer
transplantation
allogeneic
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
Collaborators: name: Ludwig-Maximilians - University of Munich
name: University of Regensburg
name: Johannes Gutenberg University Mainz
name: Charite University, Berlin, Germany
name: University Hospital Augsburg
name: BayImmuNet Bavarian Immunotherapy Network
name: German Research Foundation
First posted: 2014-08-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Toxicity of adoptive transfer of CMV/EBV specific T-cells
timeFrame: 1-28 days after adoptive T-cell transfer
Secondary outcomes:
measure: Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on virus reactivation
timeFrame: During observation period until day 204 post transplantation
measure: Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of antiviral therapy
timeFrame: During observation period until day 204 post transplantation
measure: Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of Rituximab
timeFrame: During observation period until day 204 post transplantation
measure: Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on T-cell reconstitution
timeFrame: During observation period until day 204 post transplantation
Other outcomes:
Locations:
city: Augsburg
country: Germany
facility: Medical Center Augsburg
city: Berlin
country: Germany
facility: Charité University Hospital Berlin
city: Erlangen
country: Germany
facility: Universitiy Hospital Erlangen
city: Mainz
country: Germany
facility: University of Mainz
city: Munich
country: Germany
facility: University of Munich LMU
city: Regensburg
country: Germany
facility: University of Regensburg
Study officials:
affiliation: Charite University, Berlin, Germany
name: Armin H Gerbitz, MD, PhD
role: STUDY_DIRECTOR
affiliation: University Hospital Erlangen
name: Bernd Spriewald, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Erlangen
name: Anita Kremer, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Erlangen
name: Katja San Niccolo, MD
role: PRINCIPAL_INVESTIGATOR
References: