RECRUITING

R-MVST Cells for Treatment of Viral Infections in Children and Young Adults

Conditions

Epstein-Barr Virus Cytomegalovirus Infections Adenovirus BK Virus Infection Immune Deficiency

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Single Center Phase I Study of Adoptive Immunotherapy of Refractory Viral Infection With ex Vivo Expanded Rapidly Generated Virus Specific T (R-MVST) Cells for Immunodeficient Children and Young Adults

Quick Facts

Study Start:2025-04-20

Study Completion:2030-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06926894

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:3 Months to 26 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Children and young adults (3 months to \<26 years) 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".	* 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 immunosuppressive 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. * Unable or unwilling to receive infusions at Morgan Stanley Children's Hospital.

Inclusion Criteria

Exclusion Criteria

* Children and young adults (3 months to \<26 years) 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".

* 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 immunosuppressive 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.
* Unable or unwilling to receive infusions at Morgan Stanley Children's Hospital.

Contacts and Locations

Study Contact

Prakash Satwani, MD

CONTACT

212-305-0223

ps2087@cumc.columbia.edu

Principal Investigator

Prakash Satwani, MD

PRINCIPAL_INVESTIGATOR

Professor of Pediatrics

Study Locations (Sites)

Columbia University Medical Center / New-York Presbyterian

New York, New York, 10032

United States

Collaborators and Investigators

Sponsor: Columbia University

Prakash Satwani, MD, PRINCIPAL_INVESTIGATOR, Professor of Pediatrics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-04-20

Study Completion Date2030-12

Study Record Updates

Study Start Date2025-04-20

Study Completion Date2030-12

Terms related to this study

Additional Relevant MeSH Terms

Epstein-Barr Virus
Cytomegalovirus Infections
Adenovirus
BK Virus Infection
Immune Deficiency