Rejection Chronic RenalNCT03859388
Longitudinal Changes in Donor-Derived Cell-Free DNA With Tocilizumab Treatment for Chronic Antibody-Mediated Rejection
An observational study of Rejection Chronic Renal and Kidney Transplant Rejection, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rejection Chronic Renal, Kidney Transplant Rejection
- Type of treatment
- Injection or infusion
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2019to 28 Feb 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: Use of Donor-Derived Cell-Free DNA to Characterize Response to Therapy With Tocilizumab for Chronic Antibody-Mediated Rejection in Kidney Transplantation
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.
Read the detailed description
Chronic antibody-mediated rejection (ABMR) is now recognized as the leading cause of late kidney transplant failure (1). A number of new immunosuppressive medications have been introduced to the field of kidney transplantation over the last twenty years, leading to a reduction in early acute rejection rates (2). However, long-term graft survival has not improved, primarily because of failure to make a timely diagnosis of chronic ABMR and a lack of effective therapeutic options. To date, treatment options for chronic ABMR are limited and include intravenous immunoglobulin (IVIg), rituximab, and plasmapheresis. These agents are effective for treatment of acute ABMR; however, they are generally ineffective in sustaining kidney function and prolonging graft survival in chronic ABMR.
Interleukin-6 (IL-6) blockade has emerged as a promising therapy for chronic ABMR. Our group recently reported that tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, administered monthly to patients with chronic ABMR is associated with a reduction in donor specific antibodies (DSA), stabilization of renal function, improvement in histologic features of chronic ABMR, and excellent patient and graft survival up to six years (3).
The diagnostic criteria for antibody-mediated rejection in kidney transplantation requires serologic evidence of donor-specific antibodies to human leukocyte antigen (HLA) or other antigens in conjunction with histologic findings of ABMR on biopsy for a definitive diagnosis of ABMR (4). The criteria recognize that the mere presence of DSA alone is not sufficient to classify a patient as having ABMR, as has been described previously (5). Among patients treated for ABMR, a reduction in DSA is associated with a favorable response but is only observed in a small percentage of treated patients (6). Among patients with chronic ABMR who are treated, there is a subset with persistence of high titer DSA, yet stable renal function and resolution of active lesions of ABMR on follow-up kidney biopsy. Although these patients may not warrant continuing therapy with tocilizumab, they cannot be distinguished from patients with persistently active ABMR without undergoing an additional allograft biopsy. A non-invasive test for ABMR is preferred, as allograft biopsies are invasive, resource-intensive, carry a risk of bleeding, and are time-consuming for the patient. If validated, non-invasive testing for ABMR can be useful for monitoring for a treatment response and may help guide therapy for ABMR.
Because donor-derived cell-free DNA (Allosure) is predictive of rejection n kidney transplantation, longitudinal changes in the percentage of donor-derived cell free DNA detected in plasma of kidney transplant recipients with chronic ABMR may correlate with a histologic and clinical response to treatment. The primary objective is to assess whether longitudinal changes in donor-derived cell-free DNA correlate with histologic and clinical response to treatment with tocilizumab for chronic ABMR. The secondary objectives are to assess the test performance of donor-derived cell-free DNA measured against histologic findings on biopsy, provide molecular evidence for response to tocilizumab therapy, and to describe the time course of treatment effect of tocilizumab in chronic ABMR.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the percentage of donor-derived cell-free DNA
Change in % donor-derived cell-free DNA/month
Measured: 12 months
Secondary outcomes (8)
Difference in Change in Donor-Derived Cell-Free DNA Between Responders and Non-Responders
Difference in the mean delta of donor-derived cell-free DNA from baseline to six months among histologic responders and non-responders (paired t-test)
Measured: 6 months
Change in estimated glomerular filtration rate (GFR)
Change in estimated glomerular filtration rate (GFR) measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation over 12 months from initiation of tocilizumab treatment (linear mixed effects model)
Measured: 12 months
Change in glomerulitis histology score with treatment
Change in histologic features of ABMR before and after 6 months of treatment with tocilizumab (paired t-test; g-score)
Measured: 6 months
Change in peritubular capillaritis histology score with treatment
Change in histologic features of ABMR before and after 6 months of treatment with tocilizumab (paired t-test; ptc-score)
Measured: 6 months
Change in C4d score with treatment
Change in histologic features of ABMR before and after 6 months of treatment with tocilizumab (paired t-test; C4d-score)
Measured: 6 months
Change in glomerular double contours score with treatment
Change in histologic features of ABMR before and after 6 months of treatment with tocilizumab (paired t-test; cg-score)
Measured: 6 months
Change in interstitial fibrosis score with treatment
Change in histologic features of ABMR before and after 6 months of treatment with tocilizumab (paired t-test; ci-score)
Measured: 6 months
Change in tubular atrophy score with treatment
Change in histologic features of ABMR before and after 6 months of treatment with tocilizumab (paired t-test; ct-score)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2019
- Study start1 Mar 2019
- Primary completion28 Feb 2022
- Study completion28 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Rejection Chronic RenalStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Edmund Huang, Cedars-Sinai Medical Center
- Investigators
- Edmund Huang, M.D., Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03859388
- Sponsor's protocol ID
- Pro00053105
- Status last verified
- Oct 2026
- First submitted
- 25 Feb 2019
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 22081892Meier-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.
PubMed 14961990Choi 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.
PubMed 28199785Haas 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.
PubMed 26696524Eskandary 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.
PubMed 29242250Haas 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.
PubMed 28104301
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Donor-Derived Cell-Free DNA to Characterize Response to Therapy With Tocilizumab for Chronic Antibody-Mediated Rejection in Kidney Transplantation
- ClinicalTrials.gov ID
- NCT03859388
- Acronym / sponsor ID
- Pro00053105
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 1 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Chronic antibody-mediated rejection (ABMR) is now recognized as the leading cause of late kidney transplant failure (1). A number of new immunosuppressive medications have been introduced to the field of kidney transplantation over the last twenty years, leading to a reduction in early acute rejection rates (2). However, long-term graft survival has not improved, primarily because of failure to make a timely diagnosis of chronic ABMR and a lack of effective therapeutic options. To date, treatment options for chronic ABMR are limited and include intravenous immunoglobulin (IVIg), rituximab, and plasmapheresis. These agents are effective for treatment of acute ABMR; however, they are generally ineffective in sustaining kidney function and prolonging graft survival in chronic ABMR.
Interleukin-6 (IL-6) blockade has emerged as a promising therapy for chronic ABMR. Our group recently reported that tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, administered monthly to patients with chronic ABMR is associated with a reduction in donor specific antibodies (DSA), stabilization of renal function, improvement in histologic features of chronic ABMR, and excellent patient and graft survival up to six years (3).
The diagnostic criteria for antibody-mediated rejection in kidney transplantation requires serologic evidence of donor-specific antibodies to human leukocyte antigen (HLA) or other antigens in conjunction with histologic findings of ABMR on biopsy for a definitive diagnosis of ABMR (4). The criteria recognize that the mere presence of DSA alone is not sufficient to classify a patient as having ABMR, as has been described previously (5). Among patients treated for ABMR, a reduction in DSA is associated with a favorable response but is only observed in a small percentage of treated patients (6). Among patients with chronic ABMR who are treated, there is a subset with persistence of high titer DSA, yet stable renal function and resolution of active lesions of ABMR on follow-up kidney biopsy. Although these patients may not warrant continuing therapy with tocilizumab, they cannot be distinguished from patients with persistently active ABMR without undergoing an additional allograft biopsy. A non-invasive test for ABMR is preferred, as allograft biopsies are invasive, resource-intensive, carry a risk of bleeding, and are time-consuming for the patient. If validated, non-invasive testing for ABMR can be useful for monitoring for a treatment response and may help guide therapy for ABMR.
Because donor-derived cell-free DNA (Allosure) is predictive of rejection n kidney transplantation, longitudinal changes in the percentage of donor-derived cell free DNA detected in plasma of kidney transplant recipients with chronic ABMR may correlate with a histologic and clinical response to treatment. The primary objective is to assess whether longitudinal changes in donor-derived cell-free DNA correlate with histologic and clinical response to treatment with tocilizumab for chronic ABMR. The secondary objectives are to assess the test performance of donor-derived cell-free DNA measured against histologic findings on biopsy, provide molecular evidence for response to tocilizumab therapy, and to describe the time course of treatment effect of tocilizumab in chronic ABMR.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (14 listed)
- Known contraindications for therapy with tocilizumab:
- Hypersensitivity
- Elevated liver enzymes
- Patients at risk for GI perforation
- Absolute neutrophil count <500/mm3
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in the percentage of donor-derived cell-free DNA
Time frame: 12 months
Change in % donor-derived cell-free DNA/month
8 secondary outcomes
Difference in Change in Donor-Derived Cell-Free DNA Between Responders and Non-Responders
Time frame: 6 months
Change in estimated glomerular filtration rate (GFR)
Time frame: 12 months
Change in glomerulitis histology score with treatment
Time frame: 6 months
Change in peritubular capillaritis histology score with treatment
Time frame: 6 months
Change in C4d score with treatment
Time frame: 6 months
Change in glomerular double contours score with treatment
Time frame: 6 months
Change in interstitial fibrosis score with treatment
Time frame: 6 months
Change in tubular atrophy score with treatment
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Background: PubMed 22081892Sellares 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.
- Background: PubMed 14961990Meier-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.
- Background: PubMed 28199785Choi 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.
- Background: PubMed 26696524Haas 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.
- Background: PubMed 29242250Eskandary 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.
- Background: PubMed 28104301Haas 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edmund Huang, M.D. principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rejection Chronic Renal and Kidney Transplant Rejection, run by Cedars-Sinai Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the percentage of donor-derived cell-free DNA (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03859388, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.