25BT056: Basket Study of Viral Cytotoxic T Lymphocytes

Criteria the registry did not label

• Recipient Inclusion Criteria
• Subjects with inherited (e.g. SCID) or acquired immunodeficiency with evidence of refractory viral infection with one or more of CMV, adenovirus, EBV, or BK virus. Specifically:
  • Increasing viremia by quantitative PCR with increase from baseline over 7 days, or persistent detection after 14 days despite appropriate standard of care therapy (e.g. anti-viral therapy, withdrawal of immunosuppression), AND/OR
  • Progressive symptomatic viral infection evidenced by persistent clinical symptoms or end-organ disease attributable to the viral infection that has not improved after at least 7 days of appropriate standard-of-care therapy, or develops new clinical manifestations despite standard-of-care therapy, AND/OR
  • Antiviral resistance, or inability to receive appropriate antiviral therapy due to intolerance, toxicity, contraindication, or lack of a feasible antiviral treatment option.
• Age 0 - 29 years at time of consent
• Female subjects of reproductive potential, defined per Oncology clinical guidelines as all females ≥ 12 years old, or \<12 years old who have reached menarche, must have a negative urine or serum pregnancy test. Testing may be performed using serum human chorionic gonadotropin (HCG) or urine
• Subjects with reproductive potential must agree to use an effective method of birth control
  • Recipient Exclusion Criteria
• Subjects with ≥ Grade 2 acute GVHD or moderate to severe chronic GVHD at the time of vCTL infusion
• Subjects receiving systemic steroids (\> 0.5mg/kg/day prednisolone equivalent) at the time of vCTL infusion
• Receipt of donor lymphocyte infusion within the 4 weeks preceding vCTL infusion
• Receipt of thymoglobulin, alemtuzumab, or other T cell immunosuppressive monoclonal antibody within the 4 weeks preceding vCTL infusion
• End-organ involvement of virus in sites that may, in the opinion of the investigator, put the subject at risk of unacceptable toxicity e.g. retinitis, cerebritis, encephalitis
• Known HIV infection
• Any medical condition which could compromise participation in the study, in the opinion of the investigator
• Female subjects who are pregnant or breastfeeding
  • Donor Inclusion Criteria
• Age ≥ 18 years old
• HLA match with the recipient of at least 3/6. Donor may be the original transplant donor or a third party donor
• Consent to pre screening with PepTivator testing of T cell response to the relevant virus(es)
• Willing to undergo formal donor evaluation equivalent to that required for hematopoietic stem cell transplant (HSCT) donors
• Willing to consent to T cell processing under CHOP protocol CHP784 (IRB 04 004078) using the CliniMACS device
  • Donor Exclusion Criteria
• Donors younger than 18 years old
• HLA match with the recipient less than 3/6
• Refusal or inability to consent to PepTivator pre screening
• Unwillingness or inability to undergo formal donor evaluation (as required for HSCT donors)
• Refusal or inability to consent to T cell processing under The Children's Hospital of Philadelphia protocol (CHP784, IRB 04 004078) using the CliniMACS device
• Any medical, infectious, or other condition identified during evaluation that contraindicates donation per standard HSCT donor eligibility guidelines (e.g., active uncontrolled infection, significant cardiopulmonary disease, pregnancy) or that would preclude safe apheresis/T cell collection as determined by the evaluating clinicians.