T Cell Therapy Opposing Novel COVID-19 Infection in Immunocompromised Patients
ConditionSARS-CoV-2 Infection
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age2-80
SponsorChildren's National Research Institute
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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**
Karnofsky/Lansky score >70.
≥2 years to <80 years of age at enrollment.
Disqualifiers
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.
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.
Trial design
Design model
Sequential
Treatments tested in this trial
Coronavirus-specific T cell (CST)
Biological/VaccineParticipants 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).
Treatment groups
24 Participants
are divided into 3 treatment groupsGroup A: Adults (18 to <80 years)Experimental treatment 1 intervention
Group B: Older children (12 to <18 years)Experimental treatment 1 intervention
Group C: Young children (2 to <12 years)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Within 45 days of CST infusion2
Incidence of acute Graft Vs Host Disease (aGVHD) grade ≥3
Number of patients with aGVHD grade ≥3 within 45 days of CST infusion.
Time frame
Within 45 days of CST infusion3
Incidence of Systemic Inflammatory Response Syndrome (SIRS) or CRS
Number of patients with systemic Inflammatory Response Syndrome (SIRS) or CRS
Time frame
Within 45 days of CST infusion4
Incidence of Multi-System Inflammatory Syndrome (MIS)
Number of patients with MIS
Time frame
Within 45 days of CST infusionSecondary outcomes
1
COVID-19 antiviral immunity using intracellular flow cytometry
Participant serum and PBMCs will be monitored for COVID-19 virus specific T cell activity at 45 days following CST infusion by phenotypic and functional studies including ELIspot with appropriate viral specific peptide mixtures and available HLA-restricted epitope peptides, intracellular cytokine staining, serum cytokine profiling and/or other assays as they become available for immune profiling purposes
Time frame
At 45 days following CST infusion2
COVID-19 antiviral immunity using intracellular ELIspot assays
Participant serum and PBMCs will be monitored for COVID-19 virus specific T cell activity at 45 days following CST infusion by phenotypic and functional studies including ELIspot with appropriate viral specific peptide mixtures and available HLA-restricted epitope peptides, intracellular cytokine staining, serum cytokine profiling and/or other assays as they become available for immune profiling purposes
Time frame
At 45 days following CST infusion3
Persistence of infused CSTs
Persistence of infused T cells will be monitored using deep sequencing to track the TCRB repertoire in the participant peripheral blood
Time frame
Within 12 months4
Antiviral Activity
Antiviral activity will be assessed by measurement of SARS-CoV-2 viral load by screening RT-PCR from oral/salivary samples or from respiratory samples for any participant who develops a positive SARS-CoV-2 RT-PCR post CST infusion
Time frame
Within 12 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov