NCT05183490

R-MVST Cells for Treatment of Viral Infections

Phase I Study of Adoptive Immunotherapy of Refractory Viral Infection with Ex Vivo Expanded Rapidly Generated Virus Specific T (R-MVST) Cells

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Columbia University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Starting from childhood, majority of healthy humans are exposed to common viruses such as CMV, EBV, BK and related human polyomaviruses and herpes viruses. Under normal circumstances those infections are well controlled by the adaptive immune system, but never eliminated. Instead, they are fairly inactive and produce relatively few consequences or symptoms. However, when T cell mediated immunity is suppressed, those dormant viruses reactivate and can cause a significant end-organ or severe systemic syndrome. This viral reactivation contributes to morbidity and mortality in recipients of allogeneic stem cell transplant (HCT) and solid organ transplants (SOT), and 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. As a result of a weakened immune response, conventional antiviral prophylaxis or treatment with acyclovir and ganciclovir/foscarnet (for CMV) or rituximab (against EBV) are not always effective. The main purpose of this study is to test whether giving an experimental cell product can treat the viral infection in patients who have conditions that cause poor function of their immune system, such as infections caused by viruses such as Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), BK virus, or adenovirus. The cell product is called rapidly generated virus specific T cells or R-MVST.

Conditions

• Epstein-Barr Virus Infections
• Cytomegalovirus Infections
• Adenovirus
• BK Virus Infection

Interventions

Type	Name	Description
DRUG	Rapidly generated virus specific T (R-MVST) cells	The R-MVST products will be manufactured individually for each patient from a selected donor; it is an anti-viral prophylaxis and treatment of viral reactivation. SCT dose escalation: Cohort / R-MVST dose * (-1A) 0.25x10\^6 R-MVST TNC/kg * (1A) 0.5x10\^6 R-MVST TNC/kg * (2A) 1x10\^6 R-MVST TNC/kg SOT dose escalation: Cohort / R-MVST dose * (-1B) 1x10\^6 R-MVST TNC/kg * (1B) 2x10\^6 R-MVST TNC/kg * (2B) 4x10\^6 R-MVST TNC/kg

Timeline

• Start date: 2022-05-03
• Primary completion: 2025-12-01
• Completion: 2026-12-01
• First posted: 2022-01-10
• Last updated: 2024-12-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study