Donor-Derived Cell-Free DNA for Surveillance in Simultaneous Pancreas and Kidney Transplant Recipients

The AlloSure test is approved by the Centers for Medicare & Medicaid Services (CMS) for use in Medicare patients to assess the probability of allograft rejection in kidney transplant patients. The pivotal DART study discusses the use of the non-invasive AlloSure test to measure donor derived cell-free DNA (dd-cfDNA) and the Allosure test can by used to discriminate active rejection in renal transplant patients. Pancreas allograft rejection still remains a major clinical challenge and is a primary cause of death censored pancreas allograft loss. Pancreas transplant rejection is diagnosed by biopsy, however it is not commonly performed because of the complications such as pancreatic leak, graft loss and patient death. Currently at Rush surveillance biopsy of the pancreas are not performed routinely due to the above risks.

At RUMC, patients are followed post-transplant with series of labs at set intervals that include lipase, DSA, C-Peptide, and GAD65 for surveillance of rejection

The AlloSure test was introduced for routine use in kidney transplant recipients at Rush University Medical Center in October 2017, after CMS approval and then as part of the KOAR Study in May of 2018. AlloSure test has been included as part of the routine labs for surveillance of rejection in pancreas transplant recipients at RUMC since September 2018 after it was approved for compassionate use. The addition of AlloSure has helped to improve surveillance of rejection in pancreas transplant recipients and has reduced the need for the kidney biopsy as a surrogate marker of rejection in the pancreas.

Our goal is to determine if AlloSure can be used for surveillance for rejection in recipients of Simultaneous Pancreas and Kidney (SPK) Transplant recipients.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Rejection; Pancreas Transplant Rejection
• Intervention / Treatment: Diagnostic test: Allosure Test

Detailed Description

This is a prospective and retrospective cohort study of recipients of simultaneous pancreas and kidney transplant recipients (SPK).

New SPK transplant recipients and previous SPK transplant recipients from September 2012 will be enrolled in the study, expected duration of participation will therefore range from a minimum of 1 year to a maximum of 5 years for each participant.

The visits are incorporated into the current standard of care in our program and no extra visits are required. Mobile draw for AlloSure can be obtained if the patient is not due for a visit when the AlloSure draw is due.

AlloSure labs will be drawn on all new SPK patients and results obtained as well as retrospective results that have already been received on past SPK recipients. The AlloSure will be added to the standard of care schedule for all SPK patients.

The schedule will be the following:

For newly transplanted patients, AlloSure will be checked at 14 days post-transplant

For all subjects:

From 1 month to 12 months post transplant: AlloSure will be obtained monthly with their transplant date as the reference time point

From 12 months to 36 months: AlloSure will be obtained every 3 months

From 36 months to 60 months: AlloSure will be obtained every 6 months.

AlloSure may be obtained more frequently than the above schedule, with other clinical data or allograft biopsy, if there is graft dysfunction or suspicion for rejection.

• Study Type: Observational
• Enrollment (Actual): 48

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Recipients of Simultaneous Pancreas and Kidney (SPK) transplant since 2012 and above the age of 18 will be enrolled.

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.
• New SPK transplant recipients
• SPK recipients from September 2012 with functioning kidney and pancreas, not on dialysis and/or insulin

Exclusion Criteria:

The participant may not enter the study if ANY of the following apply:

• Unwilling to participate in research study
• Recipients of other solid organ transplants apart from the SPK
• Recipients of pancreas and kidney allografts from separate donors
• Recipients with SLE
• Patients who have received a bone marrow transplant
• Recipients of a transplant form a monozygotic twin
• Patients who are pregnant
• Patients below the age of 18 years
• SPK recipient on insulin at enrolment
• SPK recipient on dialysis

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine median AlloSure level in SPK recipients with stable allograft function	Percentage of dd-cfDNA (AlloSure) level in blood samples of recipients of kidney and pancreas transplant.	Median allosure level collected from two weeks post transplant up until 36 months post transplant.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Allosure levels will be measured in the setting of rejection.	Determine AlloSure levels at time of rejection	Throughout study completion, which is three years from date of transplant.
To determine the Allosure level post transplant	AlloSure level	Throughout study completion, which is three years from date of transplant.

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Collaborators: CareDx
• Investigators: Principal Investigator: Oyedolamu Olaitan, MBBS, Rush University Medical Center

Publications and helpful links

Helpful Links

• Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications
• Cell-Free DNA and Active Rejection in Kidney Allografts.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: October 7, 2019
• First Submitted That Met QC Criteria: October 15, 2019
• First Posted (Actual): October 17, 2019

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 19073007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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