Overview

R-MVST Cells for Treatment of Viral Infections

Status:
Not yet recruiting
Trial end date:
2023-12-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Columbia University
Criteria
Recipient Inclusion Criteria:

- Men and women ages 18 years or older of all ethnic groups will be eligible for the
treatment

- Patients with history of HCT or SOT who demonstrate evidence of viral reactivation
and/or infection manifesting as end-organ or systemic disease due to one or more of
the following viruses: EBV, CMV, ADV or BK virus and suboptimal response to the
standard of care therapy.

- Recurrent or Multiple Viral Infection. RVI defined as occurrence of more than one
episode of reactivation that required intervention or symptomatic disease in recipient
of allogeneic HCT that required standard of care treatment. MVI defined as more than
one virus reactivating (defined by PCR positivity) or causing symptomatic systemic or
end-organ disease. At least one of those viral reactivations required standard of care
intervention. No standard of care therapy is defined for ADV and BK. Patients with
multiple infections/reactivations will be eligible as long as at least one of those
viral infections meet the criterium of "refractory".

Recipient Exclusion Criteria:

- Patients with other uncontrolled infections, except for CMV, EBV, ADV or BK. For
bacterial infections, patients must be receiving definitive therapy and have no signs
of progressing infection for 72 hours prior to the day of infusion. For fungal
infections, patients must be receiving definitive systemic anti-fungal therapy and
have no signs of progressing infection for 1 week prior to R-MVST infusion.
Progressing infection is defined as hemodynamic instability attributable to sepsis or
new symptoms, worsening physical signs or radiographic findings attributable to
infection. Persisting fever without other signs or symptoms will not be interpreted as
progressing infection

- Patients who receive corticosteroids at ≥ 0.5mg/kg prednisone or equivalent.

- Patients who received anti-thymocyte globulin (ATG, Alemtuzumab (Campath), or other
T-Cell immunosupressive monoclonal antibodies in the last 28 days.

- Patients who received methotrexate, or other antimetabolite-type immunosuppressants
that are toxic to proliferating T cells in the last 7 days.

- Patients who received extracorporeal photopheresis within the last 28 days.

- Patients who received checkpoint inhibitor agents (e.g., nivolumab, pembrolizumab,
ipilimumab) within 3 drug half-lives of the most recent dose to the infusion of
R-MVST.

- Received donor lymphocyte infusion in last 28 days.

- Evidence of GVHD ≥ grade 2

- Evidence of biopsy-proven acute rejection in SOT recipients

- Active and uncontrolled relapse of malignancy

- Patients who are pregnant, or breastfeeding.

- Female of childbearing potential, or male with a female partner of childbearing
potential, unwilling to use a highly effective method of contraception.

- Uncontrolled intercurrent illness including, but not limited to symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.

- Patients who have received investigational (IND) product within 14 days of infusion of
the the R-MVST cells.

Donor inclusion and exclusion criteria will be followed as per the most current BMT SOP
(Donor selection, Donor evaluation and Donor Deferral).