Assessing Benchmarks For Allosure And Allomap Testing in Simultaneous Kidney & Pancreas Transplant Recipients.

NCT04855422 | Active Not Recruiting

• 1 other identifier: 2021-12823
• Study Type: observational
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, non-interventional, prospective pilot cohort study to monitor SPK patients post-transplant to determine if non-invasive measures using dd-cfDNA (Allosure) and AlloMap can assess an array of immune panels to predict and confirm the development of allograft injury and rejection in either organ. Aims of the study

1. 1.To develop and validate AlloSure and AlloMap in SPK transplant recipients with stable allograft function and in diagnosis of acute TCMR and ABMR in either organ
2. 2.To assess the ability of AlloSure and AlloMap to determine early discordant rejection in SPK recipients
3. 3.To investigate AlloSure and AlloMap in SPK transplant recipients with diagnosis of BKV viremia

Conditions

Transplant; Complication, Rejection

Outcome Measures

Primary Outcomes (1)

• Establishing benchmarks for AlloSure and AlloMap in SPK transplant recipients with stable allograft function

  Allosure score (%) and AlloMap test score (range 0-20) in stable kidney and pancreas transplant recipients

  3, 6, 9, and 12 months after enrolment

Secondary Outcomes (1)

• To develop and validate AlloSure and AlloMap in SPK transplant recipients with diagnosis of acute TCMR and ABMR in either organ

  3, 6, 9, and 12 months after enrolment or at the time of clinically indicated kidney and/or pancreas biopsies and 2, 4, and 6 weeks after biopsy

Other Outcomes (1)

• AlloSure and AlloMap assessment in SPK transplant recipients with diagnosis of BKV viremia

  3, 6, 9, and 12 months after enrolment and at the time of BKV viremia and 2, 4 and 6 weeks after viremia

Study Arms (5)

Stable SPK recipients without rejection and/or BKV viremia

All SPK transplant recipients are monitored for routine labs twice a week first month, weekly at 2nd and 3rd month, every 2 weeks between 3-6 months, once a month between 6-12 months and then once every 2 months.

Diagnostic Test: Allosure; Diagnostic Test: AlloMap

Acute T-Cell Mediated Rejection (TCMR )

Kidney and pancreas transplant biopsies will be solely for clinically indicated for increased creatinine, amylase, lipase, blood sugar levels of more than 20% of the baseline, increased spot urine protein/creatinine ratio more than 1 gram/day, and development of donor-specific anti-Human Leukocyte Antigen (anti-HLA) antibodies.

Diagnostic Test: Allosure; Diagnostic Test: AlloMap

Antibody Medicated Rejection (ABMR)

Kidney and pancreas transplant biopsies will be solely for clinically indicated for increased creatinine, amylase, lipase, blood sugar levels of more than 20% of the baseline, increased spot urine protein/creatinine ratio more than 1 gram/day, and development of donor-specific anti-HLA antibodies.

Diagnostic Test: Allosure; Diagnostic Test: AlloMap

BKV viremia

All patients will be monitored for BKV viremia monthly after transplantation up to 6 months and at 9, 12 and 24 months. Luminex Single Antigen Bead (SAB) will be monitored at 1, 3, 12 and 24 months. Spot urine protein and creatinine and HbA1c will be monitored every 3 months after transplantation

Diagnostic Test: Allosure; Diagnostic Test: AlloMap

Follow-up of subjects with acute TCMR, ABMR and BKV viremia after treatment

BKV viremia, Luminex SAB, spot urine protein and creatinine is studied at the time clinically indicated biopsy and/o worsening kidney function and proteinuria.

Diagnostic Test: Allosure; Diagnostic Test: AlloMap

Interventions

Allosure DIAGNOSTIC_TEST

AlloSure Analysis For the AlloSure test, 10-20 mL of blood will be obtained in Streck Cell-Free DNA blood collection tubes (BCT) and shipped to CareDx, Inc. (Brisbane, CA) at ambient temperature in insulated packaging to minimize temperature fluctuation. The AlloSure test will be performed at the CareDx CLIA/CAP-accredited clinical laboratory. Samples will be tested, and results provided within 3 days of blood draw.

Acute T-Cell Mediated Rejection (TCMR ); Antibody Medicated Rejection (ABMR); BKV viremia; Follow-up of subjects with acute TCMR, ABMR and BKV viremia after treatment; Stable SPK recipients without rejection and/or BKV viremia

AlloMap DIAGNOSTIC_TEST

AlloMap Kidney is intended to aid in the identification of SPK transplant recipients who have a low probability of rejection at the time in testing in conjunction with standard clinical assessment. For the AlloMap-Kidney test, approximately two tubes of blood will be obtained in PAXgene Blood RNA tubes and shipped to CareDx, Inc. (Brisbane, CA), where it will be tested.

Acute T-Cell Mediated Rejection (TCMR ); Antibody Medicated Rejection (ABMR); BKV viremia; Follow-up of subjects with acute TCMR, ABMR and BKV viremia after treatment; Stable SPK recipients without rejection and/or BKV viremia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Simultaneous Pancreas-Kidney (SPK) transplant recipients will be enrolled at the time of transplantation or anytime within 3 years after transplantation starting at least 1 month after transplantation. Patients will have blood samples drawn at the time enrollment and at 3, 6, 9, and 12 months after enrollment and at the time of clinically indicated kidney and/or pancreas transplant biopsy. If the patients had biopsy proven acute or chronic rejection, Allosure and Allomap test will be repeated at 2, 4, and 6 weeks after the diagnosis. For patients who developed BKV viremia, Allosure and Allomap test will be tested at the time of BKV viremia and will be repeated at 2, 4, and 6 weeks after BKV viremia.

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
• SKP transplant recipients between 1 month and 3 years after transplantation

You may not qualify if:

• Previous history of solid organ transplantation
• Pregnancy

Sponsors & Collaborators

• Montefiore Medical Center: lead
• CareDx: collaborator

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Related Publications (14)

• Klassen DK, Hoen-Saric EW, Weir MR, Papadimitriou JC, Drachenberg CB, Johnson L, Schweitzer EJ, Bartlett ST. Isolated pancreas rejection in combined kidney pancreas tranplantation. Transplantation. 1996 Mar 27;61(6):974-7. doi: 10.1097/00007890-199603270-00024.

  PMID: 8623171 BACKGROUND

• Parajuli S, Arpali E, Astor BC, Djamali A, Aziz F, Redfield RR, Sollinger HW, Kaufman DB, Odorico J, Mandelbrot DA. Concurrent biopsies of both grafts in recipients of simultaneous pancreas and kidney demonstrate high rates of discordance for rejection as well as discordance in type of rejection - a retrospective study. Transpl Int. 2018 Jan;31(1):32-37. doi: 10.1111/tri.13007. Epub 2017 Aug 3.

  PMID: 28672081 BACKGROUND

• Uva PD, Odorico JS, Giunippero A, Cabrera IC, Gallo A, Leon LR, Minue E, Toniolo F, Gonzalez I, Chuluyan E, Casadei DH. Laparoscopic Biopsies in Pancreas Transplantation. Am J Transplant. 2017 Aug;17(8):2173-2177. doi: 10.1111/ajt.14259. Epub 2017 Apr 4.

  PMID: 28267898 BACKGROUND

• Bloom RD, Bromberg JS, Poggio ED, Bunnapradist S, Langone AJ, Sood P, Matas AJ, Mehta S, Mannon RB, Sharfuddin A, Fischbach B, Narayanan M, Jordan SC, Cohen D, Weir MR, Hiller D, Prasad P, Woodward RN, Grskovic M, Sninsky JJ, Yee JP, Brennan DC; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators. Cell-Free DNA and Active Rejection in Kidney Allografts. J Am Soc Nephrol. 2017 Jul;28(7):2221-2232. doi: 10.1681/ASN.2016091034. Epub 2017 Mar 9.

  PMID: 28280140 BACKGROUND

• Shen J, Zhou Y, Chen Y, Li X, Lei W, Ge J, Peng W, Wu J, Liu G, Yang G, Shi H, Chen J, Jiang T, Wang R. Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study. Transpl Int. 2019 Feb;32(2):184-192. doi: 10.1111/tri.13341. Epub 2018 Oct 2.

  PMID: 30198148 BACKGROUND

• Hurkmans DP, Verhoeven JGHP, de Leur K, Boer K, Joosse A, Baan CC, von der Thusen JH, van Schaik RHN, Mathijssen RHJ, van der Veldt AAM, Hesselink DA. Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment. J Immunother Cancer. 2019 Jul 12;7(1):182. doi: 10.1186/s40425-019-0653-6.

  PMID: 31300068 BACKGROUND

• Puliyanda DP, Swinford R, Pizzo H, Garrison J, De Golovine AM, Jordan SC. Donor-derived cell-free DNA (dd-cfDNA) for detection of allograft rejection in pediatric kidney transplants. Pediatr Transplant. 2021 Mar;25(2):e13850. doi: 10.1111/petr.13850. Epub 2020 Nov 20.

  PMID: 33217125 BACKGROUND

• Sigdel TK, Vitalone MJ, Tran TQ, Dai H, Hsieh SC, Salvatierra O, Sarwal MM. A rapid noninvasive assay for the detection of renal transplant injury. Transplantation. 2013 Jul 15;96(1):97-101. doi: 10.1097/TP.0b013e318295ee5a.

  PMID: 23756769 BACKGROUND

• Shen J, Guo L, Yan P, Zhou J, Zhou Q, Lei W, Liu H, Liu G, Lv J, Liu F, Huang H, Dong W, Shu L, Wang H, Wu J, Chen J, Wang R. Prognostic value of the donor-derived cell-free DNA assay in acute renal rejection therapy: A prospective cohort study. Clin Transplant. 2020 Oct;34(10):e14053. doi: 10.1111/ctr.14053. Epub 2020 Sep 4.

  PMID: 32735352 BACKGROUND

• Deng MC, Eisen HJ, Mehra MR, Billingham M, Marboe CC, Berry G, Kobashigawa J, Johnson FL, Starling RC, Murali S, Pauly DF, Baron H, Wohlgemuth JG, Woodward RN, Klingler TM, Walther D, Lal PG, Rosenberg S, Hunt S; CARGO Investigators. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant. 2006 Jan;6(1):150-60. doi: 10.1111/j.1600-6143.2005.01175.x.

  PMID: 16433769 BACKGROUND

• Fujita B, Prashovikj E, Schulz U, Borgermann J, Sunavsky J, Fuchs U, Gummert J, Ensminger S. Predictive value of gene expression profiling for long-term survival after heart transplantation. Transpl Immunol. 2017 Mar;41:27-31. doi: 10.1016/j.trim.2017.02.001. Epub 2017 Feb 4.

  PMID: 28167272 BACKGROUND

• Carey SA, Tecson KM, Jamil AK, Felius J, Wolf-Doty TK, Hall SA. Gene expression profiling scores in dual organ transplant patients are similar to those in heart-only recipients. Transpl Immunol. 2018 Aug;49:28-32. doi: 10.1016/j.trim.2018.03.003. Epub 2018 Mar 26.

  PMID: 29588161 BACKGROUND

• Lubetzky M, Bao Y, O Broin P, Marfo K, Ajaimy M, Aljanabi A, de Boccardo G, Golden A, Akalin E. Genomics of BK viremia in kidney transplant recipients. Transplantation. 2014 Feb 27;97(4):451-6. doi: 10.1097/01.TP.0000437432.35227.3e.

  PMID: 24310299 BACKGROUND

• Hayde N, Broin PO, Bao Y, de Boccardo G, Lubetzky M, Ajaimy M, Pullman J, Colovai A, Golden A, Akalin E. Increased intragraft rejection-associated gene transcripts in patients with donor-specific antibodies and normal biopsies. Kidney Int. 2014 Sep;86(3):600-9. doi: 10.1038/ki.2014.75. Epub 2014 Mar 26.

  PMID: 24670411 BACKGROUND

Related Links

• Isolated pancreas rejection in combined kidney pancreas transplantation
• Concurrent biopsies of both grafts in recipients of simultaneous pancreas and kidney demonstrate high rates of discordance for rejection as well as discordance in type of rejection - a retrospective study
• Laparoscopic Biopsies in Pancreas Transplantation
• Cell-Free DNA and Active Rejection in Kidney Allografts
• Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study
• Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment
• A rapid noninvasive assay for the detection of renal transplant injury
• Prognostic value of the donor-derived cell-free DNA assay in acute renal rejection therapy: A prospective cohort study
• Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling
• Gene expression profiling scores in dual organ transplant patients are similar to those in heart-only recipients
• Genomics of BK viremia in kidney transplant recipients

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Study Officials

• Enver Akalin, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: April 22, 2021
• Study Start: July 14, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)