Viral Specific T-Lymphocytes by Cytokine Capture System (CCS) to Treat Infection With Adenovirus, Cytomegalovirus or Epstein-Barr Virus After Hematopoietic Cell Transplantation or Solid Organ Transplantation and in Patients With Compromised Immunity
Summary
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.
Detailed description
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.
Arms & interventions
- BiologicalAdenovirus Specific T- Lymphocytes
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.
- BiologicalCytomegalovirus Specific T-Lymphocytes
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.
- BiologicalEpstein-Barr Virus Specific T-Lymphocytes
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.
Outcome measures
Primary
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.
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
Secondary
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)
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Viral load from Respiratory Viral Panel (RVP)
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Viral load from Bronchoalveolar lavage (BAL)
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Viral load from Urine
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Viral load from Stool
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Viral load from fluid/tissue
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Clinical response to viral specific infusion
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Number of patient who require antiviral agents
Time frame: Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion
Eligibility criteria
Study locations (3)
Jessie Alexander
Palo Alto, California, 94304
Lucile Packard Children's Hospital
Palo Alto, California, 94304
Lucile Packard Children's Hospital
Palo Alto, California, 94305