Utility of Donor-Derived Cell Free DNA in Association With Gene Expression Profiling (D-OAR)

Utility of Donor-Derived Cell-free DNA in Association With Gene-Expression Profiling (AlloMap®) in Heart Transplant Recipients (D-OAR)

Plasma donor-derived cell-free DNA (dd-cfDNA) is measured as a % of the total plasma cfDNA in association with the measurement of AlloMap, a non-invasive gene expression test to aid in heart transplant management.

Study Overview

• Status: Unknown
• Conditions: Heart Diseases; Cardiac Transplant Rejection; Cardiac Transplant Failure

Detailed Description

AlloMap Molecular Expression Testing is performed in a single laboratory, assessing the gene expression profile of RNA isolated from peripheral blood mononuclear cells (PBMC). Per FDA labeling, AlloMap Testing is "intended to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection (ACR) at the time of testing in conjunction with standard clinical assessment." AlloMap is the only non-invasive, blood test method recommended in the International Society for Heart and Lung Transplantation (ISHLT) guidelines for surveillance of heart transplant recipients for rejection. More than 52,000 commercial AlloMap tests from more than 12,000 patients have been reported by the XDx Reference Laboratory in Brisbane, California, which is certified under the Clinical Laboratory Improvement Amendment (CLIA) of 1988 and accredited by the College of American Pathologists.

In 2013, a registry study named OAR was initiated to follow long-term outcomes in allograft recipients receiving commercial AlloMap testing for surveillance (NCT01833195). The current objective is to enroll volunteers who are participating in the OAR registry(1) to co-participate in this observational sub-study, named D-OAR, in order to study a new biomarker, dd-cfDNA.

dd-cfDNA has been proposed as a marker for cellular injury caused by rejection(2, 3). Because dd-cfDNA and the AlloMap test measure different signals in the blood, a combination of the two approaches could be additive since AlloMap is a measure of host immune response and dd-cfDNA monitors graft injury.

The dd-cfDNA measurement is intended for the quantitative detection of plasma dd-cfDNA as a % of the total plasma cell-free DNA. Its utility as a surveillance tool in the management of heart transplant recipients is being investigated.

This is an observational sub-study for subjects who are co-enrolled to participate in the Outcomes AlloMap Registry (OAR). Prior to implementation of the amendment dated September 15, 2016, blood specimens were collected for assay of dd-cfDNA levels at each visit that occurred for AlloMap testing, per the OAR Study. As stated in the OAR study, the regular surveillance schedule for testing with AlloMap is determined by each participating center's standard of care. After this protocol amendment, the existing patients will no longer have routine dd-cfDNA specimens drawn to be paired with their standard of care AlloMap. The dd-cfDNA specimen will be drawn only when the patient is scheduled for a for-cause biopsy. New patients may be enrolled any time post-transplant as long as they have not had more than 1 prior AlloMap. These patients will also only undergo routine AlloMap testing as per participating center's standard of care and dd-cfDNA specimen will be drawn when the patient is scheduled for a for-cause biopsy. An AlloMap sample will be drawn for research use along with the dd-cfDNA specimen at the time of the for-cause biopsy where the center's infrastructure permits. An additional two follow-up dd-cfDNA specimens will be collected in the patients that undergo a for-cause biopsy, and are being treated for rejection and/or graft dysfunction, as per their standard of care schedule. The two follow-up visits will not be paired with a research use AlloMap and will be performed within 8 weeks after the for cause event. If a patient returns for another for-cause biopsy, the center may opt to collect another research AlloMap and dd-cfDNA specimen, and two follow-up dd-cfDNA specimens.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Preethi Prasad; Phone Number: 415-287-2558; Email: pprasad@CareDx.com

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Cedars-Sinai Medical Center
      • Contact: Sean Sana
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles
      • Contact: Ladda Douangvila
      • Principal Investigator: Eugene DePasquale, MD
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University
      • Contact: Helen Luikart
      • Principal Investigator: Kiran Khush, MD
  • Florida
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Memorial Regional Hospital
      • Contact: Ricardo Guedes
      • Principal Investigator: Ioana Dumitru, MD
    • Tampa, Florida, United States, 33606
      • Recruiting
      • Tampa General Hospital
      • Contact: Laurie Joughin
      • Principal Investigator: Peter Berman, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Virginia Bowen
      • Principal Investigator: Robert Cole, MD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
      • Contact: Daniel Rodgers
      • Principal Investigator: Jayant Raikhelkar, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • St. Vincent Medical Group
      • Contact: Melanie Wheeler
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky
      • Contact: Rebekah Evans
      • Principal Investigator: Navin Rajagopalan, MD
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Recruiting
      • Ochsner Clinic Foundation
      • Contact: Stacey Davis
      • Principal Investigator: Selim Krim, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Neha Shah
      • Principal Investigator: Monica Colvin, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Completed
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Recruiting
      • Mid America Heart Institute - St. Luke's Hospital
      • Contact: Jacqueline Smith
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Contact: Lizzy Ehrhard
      • Principal Investigator: Gregory Ewald, MD
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Hospital
      • Contact: John Donahey
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Andrea Kim
      • Principal Investigator: Farhana Latif, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Foundation
      • Contact: Barbara Gus
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Terminated
      • Integris Baptist Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Completed
      • Drexel University
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • Allegheny General Hospital
      • Contact: Laurie Machen
    • Pittsburgh, Pennsylvania, United States, 15219
      • Recruiting
      • University of Pittsburgh Medical Center
      • Contact: Traci McGaha
      • Principal Investigator: Michael Shullo, PharmD
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center
      • Contact: Ingrid Kepinski
      • Principal Investigator: Pradeep Mammen, MD
    • Dallas, Texas, United States, 75246
      • Active, not recruiting
      • Baylor Research Institute
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor St. Lukes
      • Contact: Melyssa Fink
      • Principal Investigator: Andrew Civitello, MD
  • Utah
    • Murray, Utah, United States, 84107
      • Recruiting
      • Intermountain Heart Institute
      • Contact: Anna French
      • Principal Investigator: Abdallah G Kfoury, MD
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
      • Contact: Laura Johnson
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Recruiting
      • Aurora St. Luke's Medical Center
      • Contact: Marilyn Miller
      • Principal Investigator: Nasir Sulemanjee, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Heart allograft recipients undergoing scheduled surveillance visits that are part of a long-term management plan.

Description

Inclusion Criteria

1. Any heart transplant recipient eligible for initiation and participation in the Outcomes AlloMap Registry (OAR) Study of regular AlloMap testing.
2. Patients can be enrolled any time as long as they have not had more than 1 prior AlloMap.
3. Written informed consent must be obtained prior to study enrollment. Exclusion Criteria

1. Pregnant Women.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Heart Transplant Recipients; Heart allograft recipients undergoing scheduled surveillance visits that are part of a long-term management plan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Outcomes (Vital Status of Heart Transplant Recipients)	Graft dysfunction, Rejection with hemodynamic compromise: Hemodynamic compromise is defined by the presence of one or more of the following criteria: Proportional decrease in LVEF ≥ 25%, Absolute LVEF ≤ 30%, Need for inotropic support, Cardiac index < 2.0 L/min/m2, Death (re-transplantation)	3 years

Collaborators and Investigators

• Sponsor: CareDx
• Investigators: Study Director: James P Yee, CareDx Inc (formerly XDx Inc) Brisbane, CA

Publications and helpful links

General Publications

• Grskovic M, Hiller DJ, Eubank LA, Sninsky JJ, Christopherson C, Collins JP, Thompson K, Song M, Wang YS, Ross D, Nelles MJ, Yee JP, Wilber JC, Crespo-Leiro MG, Scott SL, Woodward RN. Validation of a Clinical-Grade Assay to Measure Donor-Derived Cell-Free DNA in Solid Organ Transplant Recipients. J Mol Diagn. 2016 Nov;18(6):890-902. doi: 10.1016/j.jmoldx.2016.07.003. Epub 2016 Oct 7.
• Kobashigawa, JA. et al; Initial Analysis of the Donor-Derived Cell-Free DNA -Outcomes AlloMap Registry (D-OAR) Study in Heart Transplant Recipients Undergoing Surveillance for Rejection. 2016 ISHLT 36th Annual Meeting and Scientific Sessions. April 27-30, 2016; Washington, DC

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): February 1, 2020

Study Registration Dates

• First Submitted: June 13, 2014
• First Submitted That Met QC Criteria: June 27, 2014
• First Posted (Estimate): July 1, 2014

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Prognosis; Heart Transplantation; Risk Factors; Molecular Diagnostics
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases
• Other Study ID Numbers: SN-C-00004