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

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.

Study Overview

• Status: Terminated
• Conditions: Lung Transplant Failure and Rejection
• Intervention / Treatment: Diagnostic test: Allosure

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Allosure Arm; All subjects will be in arm one and will have AlloSure blood draws at multiple time points.

Diagnostic test: Allosure; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Primary Graft Dysfunction/Allograft Rejection 24 Hours Post Transplant	Primary Graft Dysfunction is measured using a combination of radiographic opacification and P:F ratio (ratio of partial pressure of oxygen related to fraction of inhaled oxygen). Grade 0: No opacifications on CXR Grade 1: Opacifications and P:F > 300 Grade 2: Opacifications and P:F >200, < 300 Grade 3: Opacifications and P:F < 200 If someone requires ECMO, they are automatically a grade 3.	24 hours post transplant
Number of Participants With Primary Graft Dysfunction/Allograft Rejection 48 Hours Post Transplant	Primary Graft Dysfunction is measured using a combination of radiographic opacification and P:F ratio (ratio of partial pressure of oxygen related to fraction of inhaled oxygen). Grade 0: No opacifications on CXR Grade 1: Opacifications and P:F > 300 Grade 2: Opacifications and P:F >200, < 300 Grade 3: Opacifications and P:F < 200 If someone requires ECMO, they are automatically a grade 3.	48 hours post transplant
Number of Participants With Primary Graft Dysfunction/Allograft Rejection 72 Hours Post Transplant	Primary Graft Dysfunction is measured using a combination of radiographic opacification and P:F ratio (ratio of partial pressure of oxygen related to fraction of inhaled oxygen). Grade 0: No opacifications on CXR Grade 1: Opacifications and P:F > 300 Grade 2: Opacifications and P:F >200, < 300 Grade 3: Opacifications and P:F < 200 If someone requires ECMO, they are automatically a grade 3.	72 hours post transplant
Number of Participants With Allograft Rejection 3 Months Post Transplant	Number of participants that experienced allograft rejection determined by evaluation of biopsy taken during bronchoscopy.	3 months post transplant
Number of Participants With Allograft Rejection 6 Months Post Transplant	Number of participants that experienced allograft rejection determined by evaluation of biopsy taken during bronchoscopy.	6 months post transplant
Number of Participants With Allograft Rejection 9 Months Post Transplant	Number of participants that experienced allograft rejection determined by evaluation of biopsy taken during bronchoscopy.	9 months post transplant
Number of Participants With Allograft Rejection 12 Months Post Transplant	Number of participants that experienced allograft rejection determined by evaluation of biopsy taken during bronchoscopy.	12 months post transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) Pre-Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells. Amount of Allosure Donor Derived Cell Free DNA (dd-cDNA) Pre-Transplant	pre-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 24 Hours Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	24 hours post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 48 Hours Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	48 hours post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 72 Hours Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	72 hours post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 1 Week Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	1 week post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 2 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells. Amount of Allosure Donor Derived Cell Free DNA (dd-cDNA) 2 Weeks Post Transplant	2 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 3 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	3 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 4 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	4 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 5 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	5 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 6 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	6 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 7 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	7 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 8 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	8 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 9 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	9 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 10 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	10 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 11 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	11 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 12 Weeks Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	12 weeks post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 4 Months Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	4 months post transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 5 Months Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	5 months post transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 6 Months Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	6 months post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 7 Months Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	7 months post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 8 Months Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	8 months post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 9 Months Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	9 months post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 10 Months Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	10 months post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 11 Months Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	11 months post-transplant
Amount of Allosure Donor Derived Cell Free DNA (Dd-cDNA) 12 Months Post Transplant	dd-cDNA is fragmented DNA that originates from cells and is released into the bloodstream. This fragmented DNA is donor/recipient specific. The Allosure test is able to measure the specific amount of DNA derived from the donor cells.	12 months post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants That Experienced Graft Failure or Death Within One Year Post Transplant	The number of participants that were diagnosed as having chronic lung allograft dysfunction (CLAD), needed re-transplanted or died before 1 year post transplant.	one year post transplant

Collaborators and Investigators

• Sponsor: Pablo Sanchez
• Collaborators: CareDx
• Investigators: Principal Investigator: Pablo Sanchez, MD, Associate Program Director Residency Program

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2020
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: March 17, 2020
• First Submitted That Met QC Criteria: March 19, 2020
• First Posted (Actual): March 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: STUDY19090098

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the article, after de-identification (text, tables, figures, and appendices)
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication
• IPD Sharing Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes