NCT04691622

Adoptive T Lymphocyte Administration for Chronic Norovirus Treatment in Immunocompromised Hosts

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: Children's National Research Institute · Academic / Other
• Sex: All
• Age: 3 Months – 80 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase I dose-escalation study to evaluate the safety of norovirus -specific T-cell (NST) therapy for chronic norovirus infection in participants following hematopoietic stem cell transplantation (HSCT) or who are immunocompromised due to PID and have not undergone HSCT, or Solid Organ Transplant (SOT) recipients.

Detailed description

This is an open label, phase I study of norovirus-specific T-cell immunotherapy for treatment of participants with primary immunodeficiency disorders (PID) and chronic norovirus. This study is designed to assess the safety of norovirus-specific T-cell (NST) infusion in this population. There are two arms in this study: 1. Arm A: Participants who receive donor derived NST therapy after HSCT 2. Arm B: Participants who receive partially HLA matched NSTs. The following participants apply: * Participants with PID who have not undergone HSCT. * Participants who have undergone HSCT but do not have available donor derived NSTs, or those for whom NSTs cannot be generated due to norovirus seronegativity. * Participants who have undergone SOT. Participants will be monitored for infusion-related reactions and GVHD for 1 year following first infusion. During this time, participants will be accessed with regard to the length and quantity of norovirus shedding in stool, and gastrointestinal and constitutional symptoms will be scored by clinicians and participants. Correlative studies of T-cell immune reconstitution against norovirus, norovirus genomic sequences, and composition of the fecal microbiome will also be accessed. The primary purpose of this phase I study is to assess the safety of administering donor-derived or partially HLA-matched NSTs in immunocompromised participants with chronic norovirus infections. Related and unrelated donors of participants who have chronic norovirus infection after HSCT will be enrolled for screening and production of NSTs from peripheral blood. Following product manufacturing, participants who have undergone HSCT (Arm A) will receive donor-derived NSTs. For participants with PID who have not undergone HSCT or recipients of SOT (Arm B), high-resolution HLA typing of the participant will be utilized for an inquiry of the NST bank to determine if a partially HLA-matched NST product exists that has antiviral activity mediated through one or more shared HLA alleles. Participants who have undergone HSCT but either do not have available donors for NST generation, or who have donors from whom NSTs cannot be generated due to norovirus seronegativity will also be eligible for inquiry for treatment with partially HLA-matched NSTs if available under study Arm B. This will be a dose escalation study with two arms. Participants who have undergone HSCT will be enrolled on Arm A and receive NSTs derived from their HSCT donor. Participants with a diagnosis of PID who have not undergone HSCT, recipients of SOT, or participants who have undergone HSCT but do not have available donor-derived NSTs will be enrolled on Arm B and receive partially HLA-matched NSTs. We will test three doses: 1x107 /m2, 2x107 /m2, and 4x107 /m2. Investigators will have a 45-day safety monitoring period for immediate toxicities following infusion.

Conditions

• Viral Infection
• Hematopoietic Stem Cell Transplantation (HSCT)
• Primary Immunodeficiency Disorders (PID)

Interventions

Type	Name	Description
BIOLOGICAL	Norovirus -specific T-cell (NST) therapy	Arm A: Investigators will test three doses: 1 x 107 /m2, 2 x 107 /m2, and 4 x 107 /m2. After infusion, participants will have a 45-day safety monitoring period for immediate toxicities following infusion. Arm B: Investigators will test three doses: 1 x 107 /m2, 2 x 107 /m2, and 4 x 107 /m2. After infusion, participants will have a 45-day safety monitoring period for immediate toxicities following infusion.

Timeline

• Start date: 2022-03-17
• Primary completion: 2028-08-30
• Completion: 2028-10-30
• First posted: 2020-12-31
• Last updated: 2026-01-26

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study