Viral Specific T-Lymphocytes by Cytokine Capture System (CCS) to Treat Infection With Adenovirus or Cytomegalovirus After Hematopoietic Cell Transplantation or Solid Organ Transplantation and in Patients With Compromised Immunity
Overview
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Jessie L. Alexander
- Enrollment
- 25
- Locations
- 2
- Primary Endpoint
- Grade III-IV Acute Graft versus host disease
Overview
Brief 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 and CMV 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 and CMV. 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.
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 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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Month to 65 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Received ATG or Alemtuzumab within 28 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 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.
- •Active and uncontrolled relapse of malignancy.
- •Anticipated initiation of new lymphotoxic therapy within 4 weeks of viral-specific T cell infusion.
- •Patients who are pregnant or lactating.
- •Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks to participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.
- •Donor Exclusion Criteria
- •Patients who are pregnant
Outcomes
Primary Outcomes
Grade III-IV Acute Graft versus host disease
Time Frame: Day 0 through 90 days after last cellular infusion
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
Time Frame: Day 0 through 30 days from last cellular infusion
The incidence of patients who develop CTCAE Grade 4/5 Adverse events
Secondary Outcomes
- Viral load by Polymerase Chain Reaction (PCR)(Baseline through study completion, an average of 6 months)
- Antiviral Agents(Day 0 through study completion, an average of 6 months)
- Immune Reconstitution(Baseline through study completion, an average of 6 months)
- Clinical response to viral specific infusion(Baseline through study completion, an average of 6 months as clinically indicated)
- 6-month Survival (continuous)(First cellular infusion to 6 months post first cellular infusion)
- Viral load from Bronchoalveolar lavage (BAL)(Baseline through study completion, an average of 6 months)
- Viral load from Stool(Baseline through study completion, an average of 6 months)
- Viral load from fluid/tissue(Baseline through study completion, an average of 6 months)
- Viral load from Respiratory Viral Panel (RVP)(Baseline through study completion, an average of 6 months)
- Viral load from Urine(Baseline through study completion, an average of 6 months)
Investigators
Jessie L. Alexander
Clinical Associate Professor of Pediatrics
Stanford University