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 or 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 DNA viruses. 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 or CMV infection or refractory viremia that is persistent despite standard therapy. Infusion of the cellular product will be assessed for safety and efficacy.
If a subject shows a partial response, defined as a decrease in viral load of at least 50% from baseline or 50% improvement of clinical signs and symptoms, or no response, they are eligible to receive up to 4 additional cellular infusions from the same donor, at a minimum of 14-day intervals. If the same donor is no longer available, eligible, or appropriate, another donor may be considered for a maximum of 4 total cellular infusions at the discretion of the study PI and treating physician. A subject will not exceed a maximum of 5 total infusions from 2 donors. Subjects are followed for 1 year post initial viral-specific T cell infusion. If subjects receive additional infusion(s), GvHD and adverse events will be followed for an additional 90 days from last infusion. Data may be abstracted from subjects' medical charts for an additional 1 year after most recent viral-specific T cell infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Peripheral 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.
Peripheral 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.
Peripheral 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.
UPMC (University of Pittsburgh Medical Center)
Pittsburgh, Pennsylvania, United States
Number of Patients With Grade III-IV Acute Graft Versus Host Disease
Cumulative number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.
Time frame: Day 0 through 90 days after last cellular infusion (last infusion occurred up to 38 days post day 0)
Number of Patients Who Experienced Grade 4/5 Adverse Events After Infusion
Cumulative number of patients with CTCAE Grade 4/5 Adverse events which occurred after infusion
Time frame: Day 0 through 90 days after last cellular infusion (last infusion occurred up to 38 days post day 0)
Number of Patients Who Reached 6 Month Survival
Cumulative number of patients surviving at 6 months
Time frame: First cellular infusion to 6 months post first cellular infusion (last infusion occurred up to 38 days post day 0)
Number of Patients Who Achieved One Year Survival
Cumulative number of patients who were treated and surviving one year later
Time frame: 1 year after first infusion
Patients Who Achieved Viral Response (Complete Response) to Treatment
Complete response to the virus is defined as a resolution of viremia or below limit of quantification OR complete resolution of all related clinical signs and symptoms for CMV, non lymphoproliferative EBV, and adenovirus. For lymphoproliferative EBV, complete response is defined as the resolution of related radiographic disease.
Time frame: 1, 3, and 6 months after first infusion
Number of Days to Patient Complete Response to Viral Specific Infusion
Complete response to the virus is defined as a resolution of viremia or below limit of quantification OR complete resolution of all related clinical signs and symptoms for CMV, non lymphoproliferative EBV, and adenovirus. For lymphoproliferative EBV, complete response is defined as the resolution of related radiographic disease.
Time frame: Baseline through 6 months after last infusion
Number of Days Post-VST Infusion Upon Which Viral Specific Antimicrobial Treatment Was Discontinued.
The number of days after the VST infusion that the antiviral agent used for treatment of the specific virus was stopped.
Time frame: Day 0 through 6 months after last infusion
Number of Days Post VST Infusion That Patients Achieved T Cell Immune Reconstitution
Immune reconstitution is defined as CD4 lymphocyte count greater than 50/microliter
Time frame: Baseline through 6 months after last infusion
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