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.
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 6 months 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
25
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.
Jessie Alexander
Palo Alto, California, United States
COMPLETEDLucile Packard Children's Hospital
Palo Alto, California, United States
RECRUITINGLucile Packard Children's Hospital
Palo Alto, California, United States
RECRUITINGGrade 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.
Time frame: Day 0 through 90 days after last cellular infusion
CTCAE Grade 4/5 Adverse Events
The incidence of patients who develop CTCAE Grade 4/5 Adverse events related to infusion
Time frame: Day 0 through 30 days from last cellular infusion
Number of patients achieving 6-month survival (dichotomous)
Time frame: First cellular infusion to 6 months post first cellular infusion
Viral load by Polymerase Chain Reaction (PCR)
The pace at which the viral load is undetectable in whole blood or plasma
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Viral load from Respiratory Viral Panel (RVP)
The pace at which the viral load is undetectable from nasopharyngeal swab
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Viral load from Bronchoalveolar lavage (BAL)
The pace at which the viral load is undetectable from bronchial washing
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Viral load from Urine
The pace at which the viral load is undetectable from urine sample
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Viral load from Stool
The pace at which the viral load is undetectable from stool sample
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Viral load from fluid/tissue
The pace at which the viral load is undetectable from other fluid/tissue sample
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Clinical response to viral specific infusion
By imaging and symptomatology
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Number of patient who require antiviral agents
The introduction of concomitant antiviral medication post infusion, e.g. cidofovir for adenovirus, foscarnet for CMV, rituximab for EBV
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
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