T Cell Therapy Opposing Novel COVID-19 Infection in Immunocompromised Patients
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.
‣ Participant Inclusion Criteria for CST Infusion:
• 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.
⁃ Estimated GFR \>60mL/min/1.73m2 (calculated per institutional standards).
⁃ Pulse oximetry of ≥92% on room air for at least 7 days prior to infusion.
⁃ Age appropriate mean arterial pressure without the use of vasopressors.
⁃ Negative pregnancy test in female participant of childbearing potential.
⁃ Male and female participants of childbearing potential must use highly effective birth control measures or practice abstinence for a minimum of 6 months after receiving study therapy
⁃ Written informed consent and/or signed assent line from participant, parent or guardian.
‣ Donor Inclusion Criteria:
• Donors for allogeneic (i.e. HLA matched or mismatched related or unrelated) stem cell transplants who have fulfilled eligibility as per FDA regulations outlined in 21 Code of Federal Regulations (CFR) 1271 subpart C. This includes that donors have been deemed in good health by donor physician based on physical examination and laboratory testing. If a donor has been chosen for the transplant based on urgent medical need that same donor will also be used for CST generation provided that there are no new reasons for ineligibility since the stem cell collection.
• Donor or guardian of pediatric donor capable of providing informed consent.
• 2 to 80 years of age.
• Female donors of childbearing potential must have a negative pregnancy test.