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

Sponsor

CareDx (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02178943

Collaborator

(none)

100

Enrollment

Locations

Duration (Months)

3.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Transplant Failure Cardiac Transplant Rejection Heart Diseases

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 Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

100 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Jun 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

Feb 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Heart Transplant Recipients Heart allograft recipients undergoing scheduled surveillance visits that are part of a long-term management plan.

Outcome Measures

Primary Outcome Measures

Clinical Outcomes (Vital Status of Heart Transplant Recipients) [3 years]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Beverly Hills	California	United States	90211
2	University of California, Los Angeles	Los Angeles	California	United States	90095
3	Stanford University	Stanford	California	United States	94305
4	Memorial Regional Hospital	Hollywood	Florida	United States	33021
5	Tampa General Hospital	Tampa	Florida	United States	33606
6	Emory University	Atlanta	Georgia	United States	30322
7	University of Chicago	Chicago	Illinois	United States	60637
8	St. Vincent Medical Group	Indianapolis	Indiana	United States	46260
9	University of Kentucky	Lexington	Kentucky	United States	40536
10	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
11	University of Michigan	Ann Arbor	Michigan	United States	48109
12	University of Minnesota	Minneapolis	Minnesota	United States	55455
13	Mid America Heart Institute - St. Luke's Hospital	Kansas City	Missouri	United States	64111
14	Washington University	Saint Louis	Missouri	United States	63110
15	Mount Sinai Hospital	New York	New York	United States	10029
16	Columbia University Medical Center	New York	New York	United States	10032
17	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
18	Ohio State University	Columbus	Ohio	United States	43210
19	Integris Baptist Medical Center	Oklahoma City	Oklahoma	United States	73112
20	Drexel University	Philadelphia	Pennsylvania	United States	19102
21	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
22	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15219
23	Baylor Research Institute	Dallas	Texas	United States	75246
24	UT Southwestern Medical Center	Dallas	Texas	United States	75390
25	Baylor St. Lukes	Houston	Texas	United States	77030
26	Intermountain Heart Institute	Murray	Utah	United States	84107
27	Virginia Commonwealth University	Richmond	Virginia	United States	23298
28	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215