Clinical trial NCT03924219: CMV T Cell Immunity in Pediatric Solid Organ Transplant Recipients
Official title: Assessment of CMV-specific T Cell Responses by Flow Cytometry With Intracellular Cytokine Staining to Predict CMV Infection Risk in Pediatric Solid Organ Transplant Recipients
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Heart Transplant Infection
Kidney Transplant Infection
Liver Transplant Infection
CMV
Keywords: cmv
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: ViraCor Laboratories
First posted: 2019-04-23
Enrollment: 120
Sex: ALL
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pediatric patients \<18 years of age listed or anticipated to undergo kidney, heart, or liver transplantation.

Brief summary: CMV infection and disease remain a significant clinical challenge for pediatric solid organ transplant (SOT) recipients. Current prevention strategies are limited to prophylaxis in which antiviral medication is administered for a period of several months or preemption in which close monitoring of CMV viral load from the peripheral blood is performed and treatment is initiated when CMV is detected. Each of these strategies has risks, costs, and limitations associated with it. Recently, assays for measurement of an individual patient's CMV immunity have been developed and are clinically available. One of these is the Viracor CMV T cell Immunity Panel. This flow cytometry based assay is performed on peripheral blood and measures cytokine release in response to CMV antigen stimulation by flow cytometry. The thresholds for this assay that confer protection against CMV infection in pediatric SOT recipients are not known. Defining CMV-specific cell mediated immune response thresholds that confer protection against CMV reactivation could inform patient specific durations of antiviral prophylaxis or pre-emptive surveillance testing. Therefore, the objective of this study is to quantify CMVresponsive T lymphocyte populations by flow cytometry (Viracor CMV T cell Immunity Panel) in pediatric heart, kidney, and liver transplant recipients within the first year of transplantation and to investigate potential threshold values that correlate with protection against CMV infection (DNAemia).


Eligibility criteria: Inclusion Criteria:

1. \< 18 years of age at the time of pre-transplant enrollment
2. Potential subject is undergoing evaluation or is currently listed for isolated heart, kidney, or liver transplantation at a participating transplant center OR is anticipated to undergo living-donor kidney or liver transplantation
3. Anticipated to receive ≤ 200 days of antiviral chemoprophylaxis

Note: Subjects who are consented, enrolled, and undergo transplantation at \<18 years of age will remain in the study and be followed post-transplant according to the study plan after they turn 18 years of age. Subjects will be re-consented to remain in the study at their first study visit after turning 18 years of age.

Exclusion Criteria:

I. Exclusion Criteria pre-transplant

1. Prior history of any organ transplant
2. Prior history of hematopoietic cell transplant
3. Anticipated to receive more than one organ at the time of transplant
4. Anticipated to receive \> 200 days of CMV antiviral chemoprophylaxis as part of the local transplant center's standard CMV prevention protocol
5. History of underlying primary (genetic) T cell immune deficiency

II. Exclusion Criteria post-enrollment A) Removal from study due to minimal risk for CMV infection

1. CMV seronegative children \>= 12 months of age will be enrolled pre-transplant but will subsequently be excluded from the study IF they receive an organ from a CMV seronegative donor (CMV D-/R-).
2. Infants \<12 months will be considered seronegative regardless of their CMV IgG status (whether or not this testing was obtained by the local transplant center) UNLESS the infant has a positive pre-transplant CMV culture (from urine) or a positive pre-transplant CMV PCR (from urine, saliva, or blood). Infants \<12 months of age without evidence of prior CMV infection (as defined by these preceding criteria) will be excluded from post-transplant follow up IF they receive an organ from a CMV seronegative donor due to low risk for post-transplant CMV infection. Infants \<12 months of age with evidence of prior CMV infection (as defined above) will remain in the study following transplantation.

B) Removal from study due to age

a. Subjects who are enrolled at \<18 years of age but are not transplanted prior to their 18th birthday will be removed from the study and will not have further pre- or post-transplant follow up.

Primary outcomes:
measure: CMV Infection Incidence
timeFrame: 12 months post-transplantation
Secondary outcomes:
measure: Frequency of detectable CMV T cell Immunity
timeFrame: 12 months post-transplantation
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center/Lucile Packard Children's Hospital Stanford
state: California
city: Atlanta
country: United States
facility: Emory University Medical Center/Children's Hospital of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Medical Center/Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Albert Einstein College of Medicine/Children's Hospital at Montefiore
state: New York
city: Durham
country: United States
facility: Duke University Medical Center/Duke Children's Hosptial
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center/Children's Hospital of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Daniel Dulek, MD
role: PRINCIPAL_INVESTIGATOR
References: