Utility of Donor-Derived Cell Free DNA in Association With Gene Expression Profiling

NCT ID: NCT02178943

Last Updated: 2024-10-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2020-02-29

Brief Summary

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.

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.

Conditions

Cardiac Transplant Failure; Cardiac Transplant Rejection; Heart Diseases

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Heart Transplant Recipients

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

No interventions assigned to this group

Eligibility Criteria

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.

Exclusion Criteria

1. Pregnant Women.

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

CareDx

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James P Yee

Role: STUDY_DIRECTOR

CareDx Inc (formerly XDx Inc) Brisbane, CA

Locations

Cedars-Sinai Medical Center

Beverly Hills, California, United States

University of California, Los Angeles

Los Angeles, California, United States

Stanford University

Stanford, California, United States

Memorial Regional Hospital

Hollywood, Florida, United States

Tampa General Hospital

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

University of Chicago

Chicago, Illinois, United States

St. Vincent Medical Group

Indianapolis, Indiana, United States

University of Kentucky

Lexington, Kentucky, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mid America Heart Institute - St. Luke's Hospital

Kansas City, Missouri, United States

Washington University

St Louis, Missouri, United States

Mount Sinai Hospital

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Integris Baptist Medical Center

Oklahoma City, Oklahoma, United States

Drexel University

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Baylor Research Institute

Dallas, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Baylor St. Lukes

Houston, Texas, United States

Intermountain Heart Institute

Murray, Utah, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 27727019 (View on PubMed)

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

Reference Type: RESULT

Other Identifiers

SN-C-00004

Identifier Type: -

Identifier Source: org_study_id