Longitudinal Changes in Donor-Derived Cell-Free DNA With Tocilizumab Treatment for Chronic Antibody-Mediated Rejection

NCT03859388 | Active Not Recruiting DMC

• 1 other identifier: Pro00053105
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Our group recently reported that tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, may be effective when administered monthly to patients with chronic antibody-mediated rejection (ABMR). The current paradigm to assess response to therapy involves serial monitoring for donor-specific antibodies, measurement of kidney function with creatinine, and periodic kidney transplant biopsies to survey for histologic findings indicative of ongoing ABMR. A new non-invasive blood test, donor-derived cell-free DNA (Allosure) has recently reported to have a high degree of discrimination for rejection and may be used to assess the likelihood of rejection. It has not been tested to see if it can be used to assess treatment response for rejection. This study will assess longitudinal changes in donor-derived cell-free DNA measurements in response to monthly therapy with tocilizumab for chronic ABMR and correlate these measurements to histologic changes on a follow-up kidney transplant biopsy.

Conditions

Rejection Chronic Renal; Kidney Transplant Rejection

Outcome Measures

Primary Outcomes (1)

• Change in the percentage of donor-derived cell-free DNA

  Change in % donor-derived cell-free DNA/month

  12 months

Secondary Outcomes (8)

• Difference in Change in Donor-Derived Cell-Free DNA Between Responders and Non-Responders

  6 months

• Change in estimated glomerular filtration rate (GFR)

  12 months

• Change in glomerulitis histology score with treatment

  6 months

• Change in peritubular capillaritis histology score with treatment

  6 months

• Change in C4d score with treatment

  6 months

Study Arms (1)

Chronic ABMR

Single arm; patients with chronic ABMR diagnosed by Banff 2017 criteria and recommended for monthly treatment with tocilizumab will undergo monthly testing for donor-derived cell-free DNA (Allosure) and then have a follow-up biopsy after six monthly infusions of tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult recipients of a kidney transplant alone who have chronic active ABMR on kidney transplant biopsy and are recommended for treatment with tocilizumab

You may qualify if:

• Age ≥18 years
• Enrolled within six months of biopsy-proven evidence of chronic active ABMR defined by Banff 2017 diagnostic criteria
• Evidence of DSA detected in the blood within 6 months prior to consent.
• Able to understand and provide informed consent.

You may not qualify if:

• Known contraindications for therapy with tocilizumab:
• Hypersensitivity
• Elevated liver enzymes
• Patients at risk for GI perforation
• Absolute neutrophil count \<500/mm3
• Platelet count \<50,000/mm3
• Active infection
• Contraindications for kidney transplant biopsy, including bleeding diathesis or technical/anatomical infeasibility for biopsy.
• Contraindications to donor-derived cell-free DNA (AlloSure) testing:
• Recipient of multiple transplanted organs.
• Recipient of a transplant from an identical twin.
• Pregnant
• Under the age of 18.
• Less than two weeks post-transplant.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (6)

• Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, Hidalgo LG, Famulski K, Matas A, Halloran PF. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012 Feb;12(2):388-99. doi: 10.1111/j.1600-6143.2011.03840.x. Epub 2011 Nov 14.

  PMID: 22081892 BACKGROUND

• Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004 Mar;4(3):378-83. doi: 10.1111/j.1600-6143.2004.00332.x.

  PMID: 14961990 BACKGROUND

• Choi J, Aubert O, Vo A, Loupy A, Haas M, Puliyanda D, Kim I, Louie S, Kang A, Peng A, Kahwaji J, Reinsmoen N, Toyoda M, Jordan SC. Assessment of Tocilizumab (Anti-Interleukin-6 Receptor Monoclonal) as a Potential Treatment for Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy in HLA-Sensitized Renal Allograft Recipients. Am J Transplant. 2017 Sep;17(9):2381-2389. doi: 10.1111/ajt.14228. Epub 2017 Mar 10.

  PMID: 28199785 BACKGROUND

• Haas M. The Revised (2013) Banff Classification for Antibody-Mediated Rejection of Renal Allografts: Update, Difficulties, and Future Considerations. Am J Transplant. 2016 May;16(5):1352-7. doi: 10.1111/ajt.13661. Epub 2016 Feb 4.

  PMID: 26696524 BACKGROUND

• Eskandary F, Regele H, Baumann L, Bond G, Kozakowski N, Wahrmann M, Hidalgo LG, Haslacher H, Kaltenecker CC, Aretin MB, Oberbauer R, Posch M, Staudenherz A, Handisurya A, Reeve J, Halloran PF, Bohmig GA. A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection. J Am Soc Nephrol. 2018 Feb;29(2):591-605. doi: 10.1681/ASN.2017070818. Epub 2017 Dec 14.

  PMID: 29242250 BACKGROUND

• Haas M, Mirocha J, Reinsmoen NL, Vo AA, Choi J, Kahwaji JM, Peng A, Villicana R, Jordan SC. Differences in pathologic features and graft outcomes in antibody-mediated rejection of renal allografts due to persistent/recurrent versus de novo donor-specific antibodies. Kidney Int. 2017 Mar;91(3):729-737. doi: 10.1016/j.kint.2016.10.040. Epub 2017 Jan 16.

  PMID: 28104301 BACKGROUND

Study Officials

• Edmund Huang, M.D.

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Health Sciences Associate Professor of Medicine

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: March 1, 2019
• Study Start: March 1, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)