Actively Recruiting
Adoptive T Lymphocyte Administration for Chronic Norovirus Treatment in Immunocompromised Hosts
Led by Children's National Research Institute · Updated on 2026-01-26
48
Participants Needed
3
Research Sites
8 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety of norovirus-specific T-cell (NST) therapy for people with chronic norovirus infection who have weakened immune systems due to prior hematopoietic stem cell transplantation (HSCT), primary immunodeficiency disorders (PID), or solid organ transplantation (SOT). This Phase I, open-label study aims to assess how well NST therapy is tolerated in these immunocompromised participants, focusing especially on safety outcomes like infusion reactions and graft-versus-host disease (GVHD). The study includes two treatment groups: Arm A participants who receive NSTs derived from their HSCT donor, and Arm B participants who receive partially matched NSTs from a donor bank. Both arms will test three dose levels of NST therapy: 1x10^7/m2, 2x10^7/m2, and 4x10^7/m2. After infusion, participants undergo a 45-day period of close monitoring for immediate side effects. Participants in Arm B include those with PID who have not undergone HSCT, those post-HSCT without available donor NSTs, or SOT recipients. Participants will be followed for one year after their first infusion to monitor for infusion-related reactions, GVHD, and norovirus shedding in stool. Gastrointestinal and general symptoms will be regularly assessed by clinicians and participants. The study also examines immune recovery, norovirus genetics, and gut microbiome changes. Safety and antiviral effects will be carefully evaluated, with long-term follow-up to understand the therapy's impact and tolerability.
CONDITIONS
Brief Title
Adoptive T Lymphocyte Administration for Chronic Norovirus Treatment in Immunocompromised Hosts
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Participants must be aged 3 months to 80 years.
- Prior recipients of allogeneic hematopoietic stem cell transplant (HSCT) or have primary immunodeficiency disorder (PID) without HSCT, or recipients of solid organ transplant (SOT).
- Documented chronic norovirus infection with at least two positive stool tests over a minimum of three months with symptoms.
- Steroid use must be tapered to less than 0.5 mg/kg/day prednisone (or equivalent) for at least 7 days prior to infusion.
- Stable donor chimerism for HSCT recipients within 30 days prior to infusion.
- Stable graft function without rejection in the past 2 months for SOT recipients.
- Karnofsky/Lansky performance score greater than 50.
- Adequate blood counts and organ function as defined by ANC, hemoglobin, platelets, bilirubin, AST, serum creatinine or estimated GFR, and oxygen saturation.
- Negative pregnancy test for females of childbearing age.
- Written informed consent and/or assent provided.
You will not qualify if you...
- Use of biological or immunosuppressive monoclonal antibodies targeting T cells within 28 days prior to infusion.
- Receipt of donor lymphocyte infusion, CAR T-cell therapy, or other experimental cellular therapies within 28 days prior to infusion.
- SCID patients with recent alpha/beta TCR depleted HSCT within 100 days post-transplant.
- Use of ruxolitinib or other JAK inhibitors within 7 days prior to infusion.
- Uncontrolled or progressing infections other than norovirus.
- Other active gastrointestinal infections aside from norovirus.
- Active and uncontrolled relapse of malignancy.
- Failure of primary engraftment or secondary graft failure.
- Symptomatic gastrointestinal conditions other than norovirus, including active inflammatory bowel disease or graft versus host disease grades 2 to 4.
- Receipt of small bowel transplant.
- Use of checkpoint inhibitors within 3 months prior to infusion.
- Recent intensification or alteration of immunosuppression in SOT recipients.
- Use of enteral immunoglobulin, nitazoxanide, or other experimental norovirus therapies within 28 days prior.
- Participation in other interventional trials except natural history or observational studies.
- Donor conditions posing physical or psychological risk to donation.
AI-Screening
AI-Powered Screening
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Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Single infusion with 45-day safety monitoring period for immediate toxicities following infusion.
Participants receive norovirus-specific T-cell (NST) therapy with dose escalation. The therapy is administered as an infusion of donor-derived or partially HLA-matched NSTs depending on participant group.
1 infusion visit and several monitoring visits during 45 days post-infusion
Duration - Up to 12 months following final NST infusion
Participants are monitored for infusion-related reactions, graft-versus-host disease, norovirus shedding in stool, gastrointestinal and constitutional symptoms, and immune responses for up to 12 months after the final NST infusion.
Regular visits during 12 months for assessments
Trial Site Locations
Total: 3 locations
1
Children's National Hospital
Washington D.C., District of Columbia, United States, 20010
Actively Recruiting
2
Johns Hopkins University
Baltimore, Maryland, United States, 21287
Actively Recruiting
3
National Institutes of Health (NIH)
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
M
Michael Keller, MD
F
Fahmida Hoq, MBBS, MS
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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