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

NCT06926894 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AAAV1433
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Incidence of toxicity that leads to safety endpoint

  This is to measure the incidence of toxicity post-infusion. Toxicities to consider include: GI toxicity, renal toxicity, hemorrhagic toxicity, cardiovascular toxicity hypotension, cardiac arrhythmia and left ventricular systolic dysfunction), neurological toxicity (somnolence and seizure), coagulation toxicity, vascular toxicity and pulmonary toxicity.

  Up to 28 days post R-MVST infusion

• Incidence of GVHD post-infusion that leads to safety endpoint

  This is to measure the incidence of GVHD post-infusion. The safety endpoint will be defined as de novo acute GVHD grade IV within 28 days of the last dose of R-MVST, or grades 3-5 infusion related adverse events within 28 days of the last cytotoxic T-lymphocyte (CTL) dose, or grades 4-5 non-hematological adverse events within 28 days of the last CTL dose that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.

  Up to 28 days post R-MVST infusion

Secondary Outcomes (3)

• Percentage of subjects with good response in viral load or end-organ disease improvement

  Up to 1 year after the initial R-MVST infusion

• Overall survival rate

  Up to 1 year after the initial R-MVST infusion

• Incidence of secondary graft failure

  Day 28 post R-MVST infusion

Study Arms (3)

Group A: Allogenic Stem Cell Transplant Recipients

EXPERIMENTAL

Patients who have infection due to cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus or BK virus, and are recipients of hematopoietic stem cell transplant.

Drug: Rapidly generated virus specific T (R-MVST) cells

Group B: Solid Organ Transplant Recipients

EXPERIMENTAL

Patients who have infection due to cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus or BK virus, and are recipients of solid organ transplant.

Drug: Rapidly generated virus specific T (R-MVST) cells

Group C: Other Immunocompromised Patients

EXPERIMENTAL

Patients who have infection due to cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus or BK virus, and are immunocompromised for reasons other than hematopoietic stem cell transplant or solid organ transplant.

Drug: Rapidly generated virus specific T (R-MVST) cells

Interventions

Rapidly generated virus specific T (R-MVST) cells DRUG

Group A dose escalation schedule: * Cohort (-1A): 0.25x10\^6 R-MVST TNC/kg * Cohort (1A): 0.5x10\^6 R-MVST TNC/kg * Cohort (2A): 1x10\^6 R-MVST TNC/kg Groups B \& C dose escalation schedule: * Cohort (-1B) + (-1C): 1x10\^6 R-MVST TNC/kg * Cohort (1B) + (1C): 2x10\^6 R-MVST TNC/kg * Cohort (2B) + (2C): 4x10\^6 R-MVST TNC/kg

Also known as: R-MVST infusion, total nucleated cells (TNC)

Group A: Allogenic Stem Cell Transplant Recipients; Group B: Solid Organ Transplant Recipients; Group C: Other Immunocompromised Patients

Eligibility Criteria

• Age: 3 Months - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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".

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center / New-York Presbyterian

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Epstein-Barr Virus Infections; Cytomegalovirus Infections; Adenoviridae Infections; Immunologic Deficiency Syndromes

Interventions

Cell Count

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Physiological Phenomena

Study Officials

• Prakash Satwani, MD

  Professor of Pediatrics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prakash Satwani, MD

CONTACT

212-305-0223; ps2087@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: Dose escalations will be performed separately for each group and will employ a classic 3+3 algorithmic design

Study Record Dates

• First Submitted: April 8, 2025
• First Posted: April 15, 2025
• Study Start: April 20, 2025
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)