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Clinical Trial Summary

The primary objective is to determine the safety and feasibility of administering R-MVST cells to patients with refractory viral reactivation and/or symptomatic disease caused by Epstein Barr Virus (EBV), cytomegalovirus (CMV), adenovirus (ADV) or BK virus. R-MVST cells will be generated on-demand from the closest partially human leukocyte antigen (HLA)-matched (minimum haploidentical) healthy donors or from the original allo-transplant donor if available. The investigator will closely monitor the recipients for potential toxicities including graft-versus-host disease (GVHD) post-infusion. Secondary objectives are to determine the effect of R-MVST infusion on viral load, possible recovery of antiviral immunity post-infusion and for evidence of clinical responses and overall survival. Recipients will be monitored for secondary graft failure at day 28 post R-MVST infusion.

Clinical Trial Description

Starting from childhood, majority of healthy humans are exposed to common viruses such as CMV, EBV, BK and related human polyomaviruses (JC, Merkel Cell Polyomavirus), and herpes viruses (HHV1, HHV2, HHV6). Under normal circumstances those infections are well controlled by the adaptive immune system, but never eliminated. Instead, they establish a lifelong latency that has a relatively few consequences or symptoms. However, when T cell mediated immunity is suppressed as a result of disease or as an iatrogenic side effect, those latent viruses reactivate and can cause a significant end-organ or severe systemic syndrome (Englund, Feuchtinger et al. 2011). This viral reactivation contributes to morbidity and mortality in recipients of allogeneic stem cell transplant (HCT) and solid organ transplants (SOT), but can affect many other patients who receive immunosuppressive therapies or have underlying pathology that affects T cell function, including patients with autoimmune diseases, congenital immunodeficiencies or HIV/AIDS (Tanaka, Kurosawa et al. 2016, Hill, Mayer et al. 2017). As a result of immunosuppression, conventional antiviral prophylaxis or treatment with acyclovir and ganciclovir/foscarnet (for CMV) or rituximab (against EBV) are not always effective. Furthermore, those agents present side effects, such as nephrotoxicity, myelosuppression, development of resistance, or deeper immunosuppression (Sellar and Peggs 2012). While novel pharmacotherapies, such as maribavir (Winston, Young et al. 2008) or letermovir (Chemaly, Ullmann et al. 2014), might reduce the incidence of post-transplant CMV reactivation, some of those drugs have been associated with reactivation upon discontinuation or development of resistance (Chou and Marousek 2008, Schubert, Ehlert et al. 2013, Frange and Leruez-Ville 2018). For many other viral infections, the available therapeutic options are either suboptimal or ineffective. Furthermore, viral infections create an enormous financial burden, increasing the overall cost of care for immunocompromised patients, with prolonged hospitalization and expensive therapies (Teira, Battiwalla et al. 2016). For instance, Jain et al. at NIH, Bethesda, MD estimated that patients requiring therapy for CMV reactivation incurred an additional cost of $58000 to $74000 per case (Jain, Lu et al. 2014). Rapid restoration of immune competency and establishment of long-term selfrenewing immune memory is the most reliable and potent strategy for eradicating and preventing viral infections. For many deeply immunocompromised patients, this can be accomplished by adoptive transfer of ex vivo generated antigen specific T lymphocytes targeting one or multiple viruses. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT05183490
Study type Interventional
Source Columbia University
Contact Nurse Navigator
Phone (212) 342 5162
Email [email protected]
Status Not yet recruiting
Phase Phase 1
Start date January 2022
Completion date December 2023

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