Assessment of Donor Derived Cell Free DNA and Utility in Lung Transplantation

Study Overview
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Brief Summary
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The use of Allosure to identify and quantify circulating donor-derived cell-free DNA to quantitate allograft injury in the early post-transplant period and determine its relationship to allograft failure.

Detailed Description
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Single Center Prospective Cohort Study on De-Novo Lung Transplant recipients. AlloSure will be drawn as part of routine blood draws and sent to CareDx for analysis of dd-cfDNA. All data will be collected and stored in the hospital EMR, this will be examined with the AlloSure results to correlate outcomes.

Official Title
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Assessment of Donor Derived Cell Free DNA and Utility in Lung Transplantation

Conditions
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Lung Transplant Failure and Rejection

Intervention / Treatment
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* Diagnostic Test: Allosure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is willing and able to give informed consent for participation in the study. Male or Female, aged 18 years or above. Denovo lung transplant recipient Ability to understand written and spoken English Exclusion Criteria: Previous transplant or multi-organ transplant Unable to have blood draw for medical reason

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Interventional Model Description: Correlate donor DNA in blood samples to episodes of Acute rejection diagnosed by transbronchial biopsy and BOS/CLAD diagnosed by spirometry From this correlation we hope to be able to develop a miniMally invasive test ( blood sample) that can predict or correlate acute and or chronic rejection
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allosure Arm<br>All subjects will be in arm one and will have AlloSure blood draws at multiple time points. | Diagnostic Test: Allosure<br>* Blood is collected from the patient, packaged, and shipped at ambient temperature to CareDx for testing. Donor-derived cell-free DNA is measured via targeted amplification and sequencing of a set of carefully selected and validated SNPs. The AlloSure bioinformatics software calculates the percent dd-cfDNA in the sample tested and applies the QC criteria. The AlloSure results will be compared to the episodes of acute rejection diagnosed by transbronchial biopsy and BOS/CLAD diagnosed by spirometry in the subjects medical records. Transbronchial biopsies and spirometry are standard of care for lung transplant recipients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| primary graft dysfunction/allograft rejection | incidence of dysfunction/rejection | 24 hours post transplant | 
| primary graft dysfunction/allograft rejection | incidence of dysfunction/rejection | 48 hours post transplant | 
| primary graft dysfunction/allograft rejection | incidence of dysfunction/rejection | 72 hours post transplant | 
| primary graft dysfunction/allograft rejection | incidence of dysfunction/rejection | 3 months post transplant | 
| primary graft dysfunction/allograft rejection | incidence of dysfunction/rejection | 6 months post transplant | 
| primary graft dysfunction/allograft rejection | incidence of dysfunction/rejection | 9 months post transplant | 
| primary graft dysfunction/allograft rejection | incidence of dysfunction/rejection | 12 months post transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | pre-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 24 hours post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 48 hours post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 72 hours post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 1 week post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 2 weeks post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 3 weeks post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 4 weeks post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 5 weeks post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 6 weeks post-transplant | 
| Allosure dd-cDNA | results of Allosure | 7 weeks post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 8 weeks post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 9 weeks post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 10 weeks post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 11 weeks post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 12 weeks post-transplant | 
| Allosure dd-cDNA | results of Allosure | 6 months post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 7 months post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 8 months post-transplant | 
| Allosure dd-cDNA | results of Allosure | 9 months post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 10 months post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 11 months post-transplant | 
| Allosure dd-cDNA | amount of dd-cDNA in recipient | 12 months post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of AlloSure in the predictive and prognostic value of diagnosing CLAD/allograft failure/premature death | incidence of biopsy, PFT, and AlloSure results that are correlated | From date of transplant until the date of graft failure or date of death from any cause, whichever came first, assessed up to 60 months. |