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

NCT04318587 | Terminated Results FDA Device

• 1 other identifier: STUDY19090098
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lung Transplant Failure and Rejection

Outcome Measures

Primary Outcomes (32)

• 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 Outcomes (1)

• Number of Participants That Experienced Graft Failure or Death Within One Year Post Transplant

  one year post transplant

Study Arms (1)

Allosure Arm

EXPERIMENTAL

All subjects will be in arm one and will have AlloSure blood draws at multiple time points.

Diagnostic Test: Allosure

Interventions

Allosure DIAGNOSTIC_TEST

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.

Allosure Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Previous transplant or multi-organ transplant
• Unable to have blood draw for medical reason

Sponsors & Collaborators

• Pablo Sanchez: lead
• CareDx: collaborator

Study Sites (1)

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Limitations and Caveats

Not every patient had blood collected at the specified time points. Blood was missed at time of bronchoscopy or patient cancelled their bronchoscopy. 515 blood samples drawn and shipped to CareDx. 2 samples lost after they arrived at CareDx. Of the 513 samples assessed, we were not able to get the %dd-cfDNA data for 36 samples. This was due to sample quality and assay quality metrics. Hemolysis was the main reason for incomplete data.

Results Point of Contact

• Title: Naomi Ryssel
• Organization: University of Pittsburgh

agostinonr@upmc.edu

412-335-9688

Study Officials

• Pablo Sanchez, MD

  Associate Program Director Residency Program

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice Chair, Benign Lung Diseases Surgical Director, Lung Transplant and ECMO, Director, Lung Transplant Research and ELVP Program

Model Details: 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

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 24, 2020
• Study Start: June 29, 2020
• Primary Completion: December 31, 2022
• Study Completion: December 30, 2023
• Last Updated: March 25, 2024
• Results First Posted: March 25, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.

Locations

US (1)