T Cell Therapy Opposing Novel COVID-19 Infection in Immunocompromised Patients

NCT05141058 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TONI
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open label, phase I dose-escalation study to evaluate the safety of coronavirus-specific T cell (CST) therapy for prevention of SARS-CoV-2 infection in immunocompromised patients following hematopoietic stem cell transplantation (HSCT). Participants will receive donor-derived CSTs for prevention of SARS-CoV-2 infection after HSCT (≥28 days and \<4 months after HSCT). In this dose escalation trial, three doses (1x107/m2, 2x107/m2, and 4x107/m2) will be tested for safety, with study arms for adult (≥18 years of age and \<80 years) HSCT recipients (Arm A) and two arms for pediatric (≥12 years of age and \<18 years; ≥2 years and \<12 years) HSCT recipients (Arm B and Arm C, respectively), and defined dose escalations in each study arm. The study agent will be assessed for safety (stopping rules defined) and antiviral activity.

Conditions

SARS-CoV-2 Infection

Outcome Measures

Primary Outcomes (4)

• Incidence of grade ≥3 infusion-related Adverse Events (AEs)

  Number of patients with grade ≥3 infusion-related AEs at 45 days of following CST infusion.

  Within 45 days of CST infusion

• Incidence of acute Graft Vs Host Disease (aGVHD) grade ≥3

  Number of patients with aGVHD grade ≥3 within 45 days of CST infusion.

  Within 45 days of CST infusion

• Incidence of Systemic Inflammatory Response Syndrome (SIRS) or CRS

  Number of patients with systemic Inflammatory Response Syndrome (SIRS) or CRS

  Within 45 days of CST infusion

• Incidence of Multi-System Inflammatory Syndrome (MIS)

  Number of patients with MIS

  Within 45 days of CST infusion

Secondary Outcomes (4)

• COVID-19 antiviral immunity using intracellular flow cytometry

  At 45 days following CST infusion

• COVID-19 antiviral immunity using intracellular ELIspot assays

  At 45 days following CST infusion

• Persistence of infused CSTs

  Within 12 months

• Antiviral Activity

  Within 12 months

Study Arms (3)

Adults (18 to <80 years)

EXPERIMENTAL

Arm A will include adult participants who are at least 18 years of age but younger than 80 years.

Biological: Coronavirus-specific T cell (CST)

Older children (12 to <18 years)

EXPERIMENTAL

Arm B will include adolescent participants who are at least 12 years of age but younger than 18 years.

Biological: Coronavirus-specific T cell (CST)

Young children (2 to <12 years)

EXPERIMENTAL

Arm C will include pediatric participants who are at least 2 years of age but younger than 12 years.

Biological: Coronavirus-specific T cell (CST)

Interventions

Coronavirus-specific T cell (CST) BIOLOGICAL

Participants will receive donor-derived CSTs for prevention of SARS-CoV-2 infection after HSCT (≥28 days and \<4 months after hematopoietic stem cell transplantation (HSCT).

Adults (18 to <80 years); Older children (12 to <18 years); Young children (2 to <12 years)

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• For recipient of CSTs derived from an HSCT donor under Arm A:
• a. Patients aged ≥18 years and \<80 years who were recipients of prior myeloablative or non-myeloablative allogeneic HSCT using either bone marrow or peripheral blood stem cells or single or double cord blood ≥28 days and \<4 months ago who are at risk of SARS-CoV-2 infection.
• For recipient of CSTs derived from an HSCT donor under Arms B and C:
• a. Patients aged ≥2 years and \<18 years who were recipients of prior myeloablative or non-myeloablative allogeneic HSCT using either bone marrow or peripheral blood stem cells or single or double cord blood ≥28 days and \<4 months ago who are at risk of SARS-CoV-2 infection.
• Have evidence of primary engraftment following HSCT (defined by ANC ≥500/mm3 for three consecutive measurements on different days, respectively)
• Participants receiving calcineurin inhibitors for treatment of GVHD, or for other reasons, should not have any dosage changes within 7 days prior to infusion\*\*
• a. For patients receiving steroids, dosage must have been tapered to \<0.5 mg/kg/day of prednisone (or equivalent) at least 7 days prior to infusion.
• Karnofsky/Lansky score \>70.
• ≥2 years to \<80 years of age at enrollment.
• Absolute neutrophil count (ANC) ≥500/ul.
• Hemoglobin ≥8.0g/dl (level can be achieved with transfusion).
• Platelets ≥20 K/ul (level can be achieved with transfusion)\*.
• Bilirubin ≤2x upper limit normal.
• Aspartate transaminase (AST) ≤2.5x upper limit of normal.
• Alanine transaminase (ALT) ≤2.5x upper limit of normal.

You may not qualify if:

• Participants receiving biological or immunosuppressive monoclonal antibodies targeting T cells within 28 days prior to CST infusion, including ATG, Alemtuzumab, Basiliximab, Tociluzimab, Brentuximab, or other medications under this category as determined by the investigators.
• a. If alemtuzumab has been received within 6 weeks prior to CST infusion, plasma levels should be obtained to ensure drug clearance (≤0.16 pg/ml).
• Participants who have received donor lymphocyte infusion (DLI), chimeric antigen receptor T cell infusion, or other experimental cellular therapies within 28 days prior to CST infusion.
• Participants who have received ruxolitinib or other JAK inhibitors within 7 days prior to CST infusion.
• Participants with uncontrolled or progressing infections or active infections causing fever (temperature ≥38.1°C). Uncontrolled infections are defined as bacterial, fungal, or viral infections (including HIV and Hepatitis B and C) with either clinical signs of worsening despite standard therapy that may be attributed to the uncontrolled infection. Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection.
• For bacterial infections, participants must be receiving definitive therapy and have no signs of progressing infection within 7 days prior to CST infusion.
• For fungal infections, participants must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to CST infusion.
• Participants with unexplained fever (temperature ≥38.1°C) within 7 days prior to CST infusion.
• Participants with evidence of active SARS-CoV-2 infection based on SARS-CoV-2 RT-PCR positivity.
• Participants with hypotension (mean arterial pressure \<50mmHg in participants \<5 years of age, \<55 mmHg in participants ≥5 and \<14 years of age or \<60 mmHg in participants ≥14 years of age).
• Participants with pulse pressure \>40 mmHg.
• Participants with respiratory rate \>20 breaths per minute.
• Participants with heart rate ≥140 beats per minute.
• Participants with uncontrolled hypertension as defined by systolic blood pressure \>99th percentile for age (participants \<18 years), and systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg (participants ≥18 years).
• Participants with metabolic instability.

Sponsors & Collaborators

• Children's National Research Institute: lead

Study Sites (2)

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

RECRUITING

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Susan Conway, MD

CONTACT

202-476-5845; sconway@childrensnational.org

Fahmida Hoq, MBBS

CONTACT

202-476-3634; fhoq@childrensnational.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Critical Medicine Physician

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: December 2, 2021
• Study Start: October 19, 2021
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 15, 2029
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)