The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥2/6 HLA-matched, viral specific T cells have efficacy against adenovirus, CMV, and EBV, in subjects who have previously received any type of allogeneic HCT or solid organ transplant (SOT), or have compromised immunity. Reconstitution of anti-viral immunity by donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections with adenovirus, CMV, and EBV. However, the weeks taken to prepare patient-specific products, and cost associated with products that may not be used limits their value. In this trial, we will evaluate viral specific T cells generated by gamma capture technology. Eligible patients will include HCT and/or SOT recipients, and/or patients with compromised immunity who have adenovirus, CMV, or EBV infection or refractory viremia that is persistent despite standard therapy. Infusion of the cellular product will be assessed for safety and efficacy.
Male or female, 1 month through 65 years old, inclusive, at the time of informed consent.
Prior allogeneic hematopoietic stem cell transplant, AND/OR prior solid organ transplant (liver, kidney, lung and/or heart, intestinal, pancreatic, and/or multivisceral), AND/OR diagnosis of primary immunodeficiency AND/OR current/recent administration of immunosuppressive therapy for cancer or autoimmune disease.
If receiving steroids, must be able to taper dose to less than 1 mg/kg/day prednisone (or equivalent) prior to cellular infusion.
Negative pregnancy test for females ≥10 years old or who have reached menarche, unless surgically sterilized or post-menopausal.
Received ATG or Alemtuzumab within 21 days of viral-specific T cell infusion and a lack of evidence of T cell survival, defined by <10 CD3+ T cells/uL (in unique situations, plasmapheresis may be considered).
Active acute GVHD grades II-IV.
Active severe chronic GVHD.
Received donor lymphocyte infusion, with the exception of a fraction of an umbilical cord blood, within 21 days of planned viral-specific T cell infusion. Subjects receiving a fraction of an umbilical cord blood within 21 days of the viral-specific T cell infusion will not be excluded.
Single group
Adenovirus Specific T- Lymphocytes
Biological/VaccinePeripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with Adenovirus viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system, captured and infused.
Cytomegalovirus Specific T-Lymphocytes
Biological/VaccinePeripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with Cytomegalovirus viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system, captured and infused.
Epstein-Barr Virus Specific T-Lymphocytes
Biological/VaccinePeripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with Epstein-Barr viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system, captured and infused.
Grade III-IV Acute Graft versus host disease
The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.
CTCAE Grade 4/5 Adverse Events
The incidence of patients who develop CTCAE Grade 4/5 Adverse events related to infusion
Number of patients achieving 6-month survival (dichotomous)
Viral load by Polymerase Chain Reaction (PCR)
The pace at which the viral load is undetectable in whole blood or plasma
Viral load from Respiratory Viral Panel (RVP)
The pace at which the viral load is undetectable from nasopharyngeal swab
Viral load from Bronchoalveolar lavage (BAL)
The pace at which the viral load is undetectable from bronchial washing
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Jessie L. Alexander
Lead sponsor
Stanford University
Sponsor institution
