RECRUITING

Adoptive T Lymphocyte Administration for Chronic Norovirus Treatment in Immunocompromised Hosts

Conditions

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

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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

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.

Official Title

Adoptive T Lymphocyte Administration for Chronic Norovirus Treatment in Immunocompromised Hosts

Quick Facts

Study Start:2022-03-17

Study Completion:2028-10-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04691622

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 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participants must meet one of the following criteria: 1. Recipient of prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells or single or double cord blood OR 2. Primary immunodeficiency disorder (as defined by clinical and laboratory evaluations)81 and have not undergone HSCT, OR 3. Recipients of solid organ transplant. 2. Documentation of chronic norovirus infection: 3. Participants receiving steroids for treatment of GVHD or for other reasons, dosage must have been tapered to \<0.5 mg/kg/day of prednisone (or equivalent) a minimum of 7 days prior to infusion. 4. For participants who have undergone HSCT, participants must have stable donor chimerism within the 30 days prior to NST infusion. 5. For recipients of solid organ transplants, participants must have stable graft function on maintenance immunosuppression, without evidence of rejection in the past 2 months prior to infusion, as defined by: 6. Karnofsky/Lansky score \>50 7. 3 months to 80 years of age at enrollment. 8. ANC ≥500/ul. 9. Hemoglobin ≥7.0g/dl (level can be achieved with transfusion). 10. Platelets ≥20 K/ul (level can be achieved with transfusion). 11. Bilirubin ≤2x upper limit normal. 12. AST ≤3x upper limit normal. 13. Serum creatinine ≤2x upper limit normal OR estimated GFR ≥30 ml/hr. 14. Pulse oximetry of ≥90% on room air. 15. Negative pregnancy test in female participant of childbearing age. 16. Written informed consent and/or signed assent line from participant, parent or guardian.	1. Participants receiving biological or immunosuppressive monoclonal antibodies targeting T cells within 28 days prior to NST infusion, including ATG, Alemtuzumab, Basiliximab, Tocilizumab, Brentuximab, or other medications under this category as determined by the investigators. 2. Participants who have received donor lymphocyte infusion (DLI), chimeric antigen receptor T cell infusion, or other experimental cellular therapies within 28 days prior to NST infusion. 3. Participants with SCID who have undergone α/β TCR depleted HSCT within the past 100 days post-transplant. 4. Participants who have received ruxolitinib or other JAK inhibitors within 7 days prior to NST infusion. 5. Participants with uncontrolled or progressing infections other than norovirus. Uncontrolled infections are defined as bacterial, fungal, or non-targeted viral infections with either clinical signs of worsening despite standard therapy, or chronic gastrointestinal symptoms that may be attributed to the uncontrolled infection. Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. 1. For bacterial infections, participants must be receiving definitive therapy and have no signs of progressing infection within 7 days prior to NST infusion and or no chronic gastrointestinal symptoms associated with this bacterial infection. 2. For fungal infections, participants must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to NST infusion. 6. Participants must not have other active gastrointestinal infections to which symptoms may be attributable, including parasitic infections (cryptosporidium, giardiasis), viral infections aside from norovirus (CMV colitis, rotavirus, adenovirus), or bacterial infections with C. difficile, Yersinia, Campylobacter, Salmonella, Shigella, or enteroinvasive or enterotoxigenic E. coli. 7. Participants with active and uncontrolled relapse of malignancy (if applicable). 1. Failure of primary engraftment is defined as failure to achieve platelet and/or neutrophil engraftment (ANC \<500/ul and/or platelets \<20 K/ul) following HSCT. 2. Secondary graft failure is defined as \<5% donor chimerism (CD3+ or CD34+) or permanent loss of neutrophil and/or platelet engraftment (ANC \<500/ul and/or platelets \<20 K/ul) at any time after primary engraftment. 8. Participants with symptomatic gastrointestinal conditions aside from norovirus, including active inflammatory bowel disease or graft versus host disease (grades 2 to 4). 9. Participants who have received a small bowel transplant. 10. Participants receiving checkpoint inhibitors within the previous 3 months prior to NST infusion, including nivolumab, pembrolizumab, or other related medications. 11. For SOT recipients, alteration in immunosuppression as follows: 1. Any intensification of immunosuppression (including but not limited to pulse dose corticosteroids or new biologic therapies) in the previous 2 months, 2. Alteration of maintenance immunosuppression (including changes in the number of agents or dosing goals) in the previous month. 12. Participants who have received enteral immunoglobulin, nitazoxanide, or other experimental therapies for norovirus infection within 28 days prior to NST infusion. 13. Co-enrollment in other trials is restricted, other than enrollment on natural history or observational studies. Study staff should be notified of co-enrollment as it may require the approval of the investigator or sponsor.

Inclusion Criteria

Exclusion Criteria

1. Participants must meet one of the following criteria:
1. Recipient of prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells or single or double cord blood OR
2. Primary immunodeficiency disorder (as defined by clinical and laboratory evaluations)81 and have not undergone HSCT, OR
3. Recipients of solid organ transplant.
2. Documentation of chronic norovirus infection:
3. Participants receiving steroids for treatment of GVHD or for other reasons, dosage must have been tapered to \<0.5 mg/kg/day of prednisone (or equivalent) a minimum of 7 days prior to infusion.
4. For participants who have undergone HSCT, participants must have stable donor chimerism within the 30 days prior to NST infusion.
5. For recipients of solid organ transplants, participants must have stable graft function on maintenance immunosuppression, without evidence of rejection in the past 2 months prior to infusion, as defined by:
6. Karnofsky/Lansky score \>50
7. 3 months to 80 years of age at enrollment.
8. ANC ≥500/ul.
9. Hemoglobin ≥7.0g/dl (level can be achieved with transfusion).
10. Platelets ≥20 K/ul (level can be achieved with transfusion).
11. Bilirubin ≤2x upper limit normal.
12. AST ≤3x upper limit normal.
13. Serum creatinine ≤2x upper limit normal OR estimated GFR ≥30 ml/hr.
14. Pulse oximetry of ≥90% on room air.
15. Negative pregnancy test in female participant of childbearing age.
16. Written informed consent and/or signed assent line from participant, parent or guardian.

1. Participants receiving biological or immunosuppressive monoclonal antibodies targeting T cells within 28 days prior to NST infusion, including ATG, Alemtuzumab, Basiliximab, Tocilizumab, Brentuximab, or other medications under this category as determined by the investigators.
2. Participants who have received donor lymphocyte infusion (DLI), chimeric antigen receptor T cell infusion, or other experimental cellular therapies within 28 days prior to NST infusion.
3. Participants with SCID who have undergone α/β TCR depleted HSCT within the past 100 days post-transplant.
4. Participants who have received ruxolitinib or other JAK inhibitors within 7 days prior to NST infusion.
5. Participants with uncontrolled or progressing infections other than norovirus. Uncontrolled infections are defined as bacterial, fungal, or non-targeted viral infections with either clinical signs of worsening despite standard therapy, or chronic gastrointestinal symptoms that may be attributed to the uncontrolled infection. Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
1. For bacterial infections, participants must be receiving definitive therapy and have no signs of progressing infection within 7 days prior to NST infusion and or no chronic gastrointestinal symptoms associated with this bacterial infection.
2. For fungal infections, participants must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to NST infusion.
6. Participants must not have other active gastrointestinal infections to which symptoms may be attributable, including parasitic infections (cryptosporidium, giardiasis), viral infections aside from norovirus (CMV colitis, rotavirus, adenovirus), or bacterial infections with C. difficile, Yersinia, Campylobacter, Salmonella, Shigella, or enteroinvasive or enterotoxigenic E. coli.
7. Participants with active and uncontrolled relapse of malignancy (if applicable).
1. Failure of primary engraftment is defined as failure to achieve platelet and/or neutrophil engraftment (ANC \<500/ul and/or platelets \<20 K/ul) following HSCT.
2. Secondary graft failure is defined as \<5% donor chimerism (CD3+ or CD34+) or permanent loss of neutrophil and/or platelet engraftment (ANC \<500/ul and/or platelets \<20 K/ul) at any time after primary engraftment.
8. Participants with symptomatic gastrointestinal conditions aside from norovirus, including active inflammatory bowel disease or graft versus host disease (grades 2 to 4).
9. Participants who have received a small bowel transplant.
10. Participants receiving checkpoint inhibitors within the previous 3 months prior to NST infusion, including nivolumab, pembrolizumab, or other related medications.
11. For SOT recipients, alteration in immunosuppression as follows:
1. Any intensification of immunosuppression (including but not limited to pulse dose corticosteroids or new biologic therapies) in the previous 2 months,
2. Alteration of maintenance immunosuppression (including changes in the number of agents or dosing goals) in the previous month.
12. Participants who have received enteral immunoglobulin, nitazoxanide, or other experimental therapies for norovirus infection within 28 days prior to NST infusion.
13. Co-enrollment in other trials is restricted, other than enrollment on natural history or observational studies. Study staff should be notified of co-enrollment as it may require the approval of the investigator or sponsor.

Contacts and Locations

Study Contact

Michael Keller, MD

CONTACT

202-476-5843

MKeller@childrensnational.org

Fahmida Hoq, MBBS, MS

CONTACT

202-476-3634

fhoq@childrensnational.org

Principal Investigator

Michael Keller, MD

PRINCIPAL_INVESTIGATOR

CNH

Study Locations (Sites)

Children's National Hospital

Washington, District of Columbia, 20010

United States

Johns Hopkins University

Baltimore, Maryland, 21287

United States

National Institutes of Health (NIH)

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: Children's National Research Institute

Michael Keller, MD, PRINCIPAL_INVESTIGATOR, CNH

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 Date2022-03-17

Study Completion Date2028-10-30

Study Record Updates

Study Start Date2022-03-17

Study Completion Date2028-10-30

Terms related to this study

Additional Relevant MeSH Terms

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