R-MVST cell therapy for viral infections in children and young adults

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

This will try giving rapidly generated virus-specific T cells (R-MVST) to children and young adults whose weakened immune systems have recurrent or treatment-resistant infections with EBV, CMV, adenovirus, or BK virus.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 3 Months to 26 Years
• Sex: All
• Sponsor: Columbia University (Academic / other)
• Drugs / interventions: Alemtuzumab, nivolumab, pembrolizumab, ipilimumab, methotrexate, prednisone, rituximab
• Locations: 1 site (New York, New York)
• Trial ID: NCT06926894 on ClinicalTrials.gov

What this trial studies

This single-center Phase 1 trial tests the safety and feasibility of infusing rapidly generated virus-specific T cells (R-MVST) into pediatric and young adult patients with refractory viral reactivation or symptomatic disease. R-MVST products are made on-demand from the closest partially HLA-matched healthy donor (minimum haploidentical) or from the original allo-transplant donor when available, and recipients will be closely monitored for toxicities including graft-versus-host disease. Secondary goals include measuring effects on viral load, recovery of antiviral immunity, clinical responses, overall survival, and monitoring for secondary graft failure at day 28 after infusion. Participants are children and young adults with prior HCT or SOT or other causes of T-cell dysfunction who have had suboptimal responses to standard antiviral therapies.

Who should consider this trial

Good fit: Children and young adults aged 3 months to under 26 years with a history of allogeneic HCT or solid organ transplant (or other T-cell dysfunction) who have refractory, recurrent, or multiple viral reactivations with suboptimal response to standard therapy are ideal candidates.

Not a fit: Patients who have well-controlled viral infections on standard antiviral treatment, who fall outside the age range, or who lack a suitable HLA-matched donor are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this therapy could restore antiviral T-cell immunity, lower viral loads, and reduce organ damage and complications from EBV, CMV, adenovirus, or BK infections in immunocompromised pediatric patients.

How similar studies have performed: Related donor-derived and third-party virus-specific T-cell therapies have shown promising results in transplant recipients, though rapidly generated on-demand products are newer and less extensively tested in large trials.

Eligibility criteria

Inclusion 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".

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 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.

Where this trial is running

New York, New York

• Columbia University Medical Center / New-York Presbyterian — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Prakash Satwani, MD — Professor of Pediatrics
• Study coordinator: Prakash Satwani, MD

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