Abstract CT028: Adoptive transfer of CMV- and EBV- specific peptide-stimulated T cells after allogeneic stem cell transplantation: A Phase I/IIa clinical trial
Authors: Aigner Michael , Gary Regina , Moosmann Andreas , Maas Stefanie , Strobl Julian , Zimmermann Robert , Zingsem Jürgen , Kremer Anita , Mackensen Andreas , Gerbitz Armin 
Published: July 2017

Abstract
Allogeneic stem cell transplantation (ASCT) to date is the only permanent curative treatment for many hematological cancers. Besides the development of Graft versus Host disease (GvHD), infections are the major adverse effect of ASCT. Specifically, reactivation of viruses is highly problematic in the aftermath of ASCT. Reactivation of human CMV and EBV negatively impacts on outcome after ASCT. 40-50% of patients reactivate CMV following ASCT, while the only CMV specific antiviral therapy available is ganciclovir, with other drugs being used off-label. For the 20-30% of patients reactivating EBV, only rituximab is available to control EBV. Rituximab leads to long term B-cell depletion requiring frequent administration of immunoglobulins. To cover this unmet medical need of CMV and EBV control after ASCT, we investigate a somatic cell therapy approach by adoptive transfer of CMV- and EBV-specific peptide-stimulated T cells. We specifically are scrutinizing the effect of application of the cells to prevent virus reactivation before its onset or preemptively at the early stages of viral infection. We set up a prospective randomized controlled phase I/IIa multi-center clinical trial to evaluate the safety and efficacy of preventive and preemptive adoptive transfer of this ATMP in patients after ASCT (EudraCT number 2012-004240-30). The design of the trial allows to applicate low numbers of activated T cells, thereby reducing the potential risks of GvHD for the recipient of adoptively transferred T cells. The multi-center trial is currently recruiting, so far, 13 patients have been randomized. ASCT patients are randomly assigned to the intervention or control group. Subjects of the control group receive standard of care. For all subjects of the intervention group, a personalized cell product (ATMP) containing a standardized number of virus specific T cells is manufactured from an aliquot of the leukapheresis product previously used for ASCT and cryopreserved until being administered. Subjects receive the cell product in intervals of at least 30 days, starting with the first adoptive transfer 30 days after ASCT at the earliest. Cells are transferred as preventive, preemptive, or also as therapeutic treatment. Subjects are monitored for occurrence of GvHD, for viral load, as well as for immune reconstitution and composition of the TCR pool, especially of virus-specific T cells.
Citation Format: Michael Aigner, Regina Gary, Andreas Moosmann, Stefanie Maas, Julian Strobl, Robert Zimmermann, Jürgen Zingsem, Anita Kremer, Andreas Mackensen, Armin Gerbitz. Adoptive transfer of CMV- and EBV- specific peptide-stimulated T cells after allogeneic stem cell transplantation: A Phase I/IIa clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT028. doi:10.1158/1538-7445.AM2017-CT028