Clinical trial NCT02424227: Non Invasive Blood Test To Diagnose Acute Rejection After Kidney Transplantation
Official title: Circulating Donor-Derived Cell-free DNA in Blood for Diagnosing Acute Rejection in Kidney Transplant Recipients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Kidney Transplant Recipients
Lead sponsor: CareDx
Sponsor class: INDUSTRY
First posted: 2015-04-22
Enrollment: 401
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult de novo living and deceased donor kidney transplant recipients will be eligible to participate in this study.

Brief summary: This is a prospective, multicenter, observational study of kidney transplant subjects where blood specimens, intended for dd-cfDNA and other future research purposes, will be drawn after transplant

Detailed description: This is a prospective, multicenter, observational study of kidney transplant subjects where blood specimens, intended for dd-cfDNA and other future research purposes, will be drawn after transplant periodically and also after the treatment of acute rejection up to 8 weeks post treatment. The blood samples and all relevant clinical data will be provided to CareDx scientists for laboratory assay of dd-cfDNA levels and correlation of dd-cfDNA levels with the clinical features of the subjects.

The primary objective of the study is to correlate circulating dd-cfDNA to clinical and sub-clinical acute rejection in renal allograft recipients. The secondary objective of the study is to correlate circulating dd-cfDNA to renal function, both serum creatinine and estimated glomerular filtration rate \[eGFR\]).

Eligibility criteria: Inclusion Criteria

1. Adult recipients (Age \> 18 years )
2. Both genders and all racial and ethnic groups
3. Kidney transplant alone
4. Both living and deceased donor transplants
5. Primary and re-transplants. A total of 30 re-transplant recipients across all study sites will be eligible for enrollment. CareDx will notify all centers when this subset of enrollment has been met. Thereafter, all enrolled patients should be primary transplant recipients.
6. Ability to come for follow-up and undergo biopsy (Performed in accordance to SOC)
7. Ability to give written informed consent prior to study enrollment

Patients can be enrolled at any time; before or after transplantation and/or at time of outpatient or inpatient visits for workup of medical problems; e.g. at the time of a renal biopsy (regardless of elapsed time since post transplant) as specified in this study protocol.

Exclusion Criteria

1. Pediatric recipients (Age \< 18 years)
2. Pregnant women
3. Patients undergoing multi-organ transplants (e.g. kidney with pancreas or liver)
4. Patients receiving donor organ from an identical twin

Primary outcomes:
measure: Clinical T cell as well as antibody mediated acute rejection
timeFrame: Occurring within 12 months post transplant
measure: Sub-clinical T cell as well as antibody mediated acute rejection
timeFrame: Occurring within 12 months post transplant
measure: Composite of clinical and sub-clinical T cell as well as antibody mediated acute rejection
timeFrame: Occurring within 12 months post transplant
Secondary outcomes:
measure: eGFR (estimated Glomerular Filtration Rate [mL/min]): will be derived from serum creatinine level, corrected for variables, using the CKD-RPI (Chronic Kidney Disease Epidemiology Collaboration) equation
timeFrame: 24 months
measure: Renal allograft injury from BKV nephritis, CNI toxicity, acute pyeloenephrtiis and recurrent disease confirmed by renal histology
timeFrame: 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvannia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: Baylor Research Institute
state: Texas
city: Temple
country: United States
facility: Baylor Scott and White
state: Texas
Study officials:
affiliation: CareDx
name: James Yee, MD
role: STUDY_DIRECTOR
References:
citation: Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MC, David DS, David-Neto E, Bagnasco SM, Cendales LC, Cornell LD, Demetris AJ, Drachenberg CB, Farver CF, Farris AB 3rd, Gibson IW, Kraus E, Liapis H, Loupy A, Nickeleit V, Randhawa P, Rodriguez ER, Rush D, Smith RN, Tan CD, Wallace WD, Mengel M; Banff meeting report writing committee. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014 Feb;14(2):272-83. doi: 10.1111/ajt.12590.
citation: Lo YM. Transplantation monitoring by plasma DNA sequencing. Clin Chem. 2011 Jul;57(7):941-2. doi: 10.1373/clinchem.2011.166686. No abstract available.
citation: Snyder TM, Khush KK, Valantine HA, Quake SR. Universal noninvasive detection of solid organ transplant rejection. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6229-34. doi: 10.1073/pnas.1013924108. Epub 2011 Mar 28.
citation: Code of Federal Regulations, Title 42 - Public Health, Part 493 - Laboratory Requirements, Subpart A - General Provisions, Sections 1, 2 & 3
citation: Hidestrand M, Tomita-Mitchell A, Hidestrand PM, Oliphant A, Goetsch M, Stamm K, Liang HL, Castleberry C, Benson DW, Stendahl G, Simpson PM, Berger S, Tweddell JS, Zangwill S, Mitchell ME. Highly sensitive noninvasive cardiac transplant rejection monitoring using targeted quantification of donor-specific cell-free deoxyribonucleic acid. J Am Coll Cardiol. 2014 Apr 1;63(12):1224-1226. doi: 10.1016/j.jacc.2013.09.029. Epub 2013 Oct 16. No abstract available.
citation: 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.
citation: De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Bernstein D, Weisshaar D, Quake SR, Khush KK. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014 Jun 18;6(241):241ra77. doi: 10.1126/scitranslmed.3007803.
citation: Sawinski DL, Mehta S, Alhamad T, Bromberg JS, Fischbach B, Aeschbacher T, Ghosh S, Shekhtman G, Dholakia S, Brennan DC, Poggio E, Bloom RD, Jordan SC. Association between dd-cfDNA levels, de novo donor specific antibodies, and eGFR decline: An analysis of the DART cohort. Clin Transplant. 2021 Sep;35(9):e14402. doi: 10.1111/ctr.14402. Epub 2021 Jul 14.
citation: Bromberg JS, Brennan DC, Poggio E, Bunnapradist S, Langone A, Sood P, Matas AJ, Mannon RB, Mehta S, Sharfuddin A, Fischbach B, Narayanan M, Jordan SC, Cohen DJ, Zaky ZS, Hiller D, Woodward RN, Grskovic M, Sninsky JJ, Yee JP, Bloom RD. Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications. J Appl Lab Med. 2017 Nov 1;2(3):309-321. doi: 10.1373/jalm.2016.022731.