Chronic Antibody-mediated Transplant RejectionPhase 2TRIBUTENCT02201576
Bortezomib in Rejection of Kidney Transplants
A Phase 2 study testing Bortezomib and Plasma exchanges and intravenous immunoglobulins in people with Chronic Antibody-mediated Transplant Rejection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The purpose of the study is to assess the efficacy of bortezomib, in association with steroids, plasma exchange, and polyclonal intravenous immunoglobulins, in the treatment of chronic antibody mediated rejection due to donor specific anti-HLA antibodies, in kidney transplant recipients Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Antibody-mediated Transplant Rejection
- What is being tested?
- Bortezomib and Plasma exchanges and intravenous immunoglobulins
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- 11 Feb 2015to 16 Jul 2020
- Phase
- Phase 2
- 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
Who may be able to join
- recipients of a first or a second kidney transplant for more than 3 months
- age over 18 years
- with de novo donor specific antibodies (DSA), i.e. antibodies not detected the day of transplantation and in pre-transplant sera
- with histological lesions of chronic active antibody-mediated rejection (glomerulitis + peritubular capillaritis banff score and chronic glomerulopathy (g+ptc ≥ 2) on a graft biopsy performed because of renal function deterioration, proteinuria, detection of de novo DSA, or on a systematic biopsy
- written informed consent
- Given the teratogenic risks described in the SPCs of Velcade and Cellcept:
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- Women of child bearing age must have a negative pregnancy test the day of the inclusion and should use at least one effective contraceptive method before start of medication during the treatment and during the study
- Men old enough to procreate have to use condoms during the treatment and at least 90 days after the last intake of the treatment during the study. Moreover, given SPCs of Cellcept, it is recommended that female partners to use an effective method of contraception treatment and for 90 days after the last mycophenolate intake by the partner male
- affiliated with social security health insurance
- patients with cell rejection lesions associated with chronic humoral rejection lesions active may be included in the study. This rejection can be treated with 3 boluses of 500 mg of methyl prednisolone prior to inclusion.
Who cannot join
- patient with preformed DSA
- recipient of a 3rd or 4th kidney transplant
- recipient of a transplant combined with another not renal organ
- patient with a history of humoral acute rejection during the current transplantation
- estimated GFR below 20 ml/min/1,73m2
- severe transplant glomerulopathy (cg score = 3)
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- severe peripheral neuropathy, thrombopenia < 100 000 mm3 , neutropenia < 1000 mm3 and/or an uncontrolled evolutionary infection
- chronic active hepatitis B (positive HBs antigen or HBV DNA), positive chronic hepatitis C and/or known HIV infection
- allergy to bore or bortezomib or to one of the excipient
- hepatic failure, abnormal liver tests (bilirubin >3N, transaminases >3n), infiltrative pneumopathy, pericarditis
- risk of non-adherence to treatment or protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of Chronic Active Antibody-mediated Rejection With Bortezomib in Kidney Transplantation
The purpose of the study is to assess the efficacy of bortezomib, in association with steroids, plasma exchange, and polyclonal intravenous immunoglobulins, in the treatment of chronic antibody mediated rejection due to donor specific anti-HLA antibodies, in kidney transplant recipients
Read the detailed description
Chronic active antibody-mediated rejection (AMR) is considered as a main cause of late allograft losses in kidney transplant recipients. It is due to the occurrence of de novo donor-specific anti-HLA antibodies (DSA), i.e. antibodies synthetized by the recipient after transplantation against its transplant. There is currently to efficient treatment. The purpose of our study is to determine the efficacy of bortezomib, a proteasome inhibitor, in the treatment of chronic active antibody-mediated rejection, in association with steroids, plasma exchanges, and polyclonal intravenous immunoglobulins. Patients are recipients of a first or a second kidney transplant for more than 3 months. They display de novo DSA i.e. DSA not detected the day of transplantation and in pre-transplant sera.. They display signs of chronic active AMR on kidney biopsy i.e. a glomerulitis (g) + peritubular capillaritis (ptc) Banff score g+ptc ≥ 2, with or without severe chronic glomerulopathy (Banff score cg<3). Kidney biopsy may have been performed systematically or because of: :
- detection of de novo DSA ,
- and /or proteinuria (> 0.5 g/24h)
- and /or slow graft dysfunction protocol biopsy Primary endpoint is a combined endpoint one year after inclusion, consisting of the stabilization of histological lesions on a new kidney biopsy (delta g+ptc ≤1 and delta cg < 1) and a decrease in DSA mean fluorescence intensity > 50%.
- Being tested
- Bortezomib, Plasma exchanges and intravenous immunoglobulins
- Keywords
- Chronic antibody-mediated rejection,, transplant rejection, kidney transplantation,, proteasome inhibitor,, anti-HLA antibodies,, immunosuppressive agents
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
- Five plasma exchanges +0.1 g/kg of intravenous immunoglobulins at the end of each course
- two cycles of bortezomib (1.3 mg/m2 IV at day-1, day-4, day-8, day-11) + oral dexamethasone (20 mg po at day-1, day-4, day-8, day-11)
- four courses of polyclonal intravenous immunoglobulins every three weeks (2g/kg, the first two courses are performed simultaneously with the two bortezomib cycles)
Plasma exchanges and intravenous immunoglobulinsDrug
- Five plasma exchanges +0.1 g/kg of intravenous immunoglobulins at the end of each course
- four courses of polyclonal intravenous immunoglobulins every three weeks (2g/kg)
- oral dexamethasone (20 mg po at day-1, day-3, day-5, day-7 of the two first intravenous immunoglobulins courses)
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib | Experimental | Five plasma exchanges, two cycles of bortezomib + dexamethasone, 4 courses of polyclonal intravenous immunoglobulins Receives: Drug: Bortezomib |
| Control | Active comparator | Five plasma exchanges, dexamethasone, 4 courses of polyclonal intravenous immunoglobulins Receives: Drug: Plasma exchanges and intravenous immunoglobulins |
What is being measured
The primary outcome is the main question the study is designed to answer.
histological lesions of humoral rejection and immunodominant donor specific antibody
Between inclusion biopsy and end of study biopsy delta g+ptc ≤1 and delta cg < 1 (Banff score of glomerulitis (g) capillaritis (ptc) and chronic allograft glomerulopathy (cg) Between inclusion and end of study, decrease in mean fluorescence intensity (MFI) of the immunodominant donor specific anti-HLA antibody (DSA with the highest MFI) by Luminex greater than 50%
Measured: one year
Secondary outcomes (9)
histological lesions of humoral rejection
Between inclusion biopsy and end of study biopsy delta g+ptc ≤1 and delta cg < 1 (Banff score of glomerulitis (g) capillaritis (ptc) and chronic allograft glomerulopathy (cg)
Measured: one year
immunodominant donor specific antibody
Between inclusion and end of study, decrease in mean fluorescence intensity (MFI) of the immunodominant donor specific anti-HLA antibody (DSA with the highest MFI) by Luminex greater than 50%
Measured: one year
all donor specific antibodies at one year
Between inclusion and end of study, variation of the title of each DSA and the sum of the DSAs
Measured: one year
all donor specific antibodies
Between inclusion and month-6, evolution in mean fluorescence intensity (MFI) of all donor specific anti-HLA antibodies by Luminex
Measured: 6 months
Histological lesions
Description of all histological lesions observed at one-year biopsy according to the Banff classification and comparison with inclusion biopsy: acute cellular rejection, interstitial fibrosis and tubular atrophy, chronic vascular lesions (arteriolar hyalinosis, fibro-intimal thickening), chronic rejection (transplant glomerulopathy, fibroproliferative endarteritis)
Measured: one year
renal function and proteinuria
Evolution between inclusion and end of study at one-year of serum creatinine, estimated GFR (MDRD formula), proteinuria output, proteinuria/creatinuria ratio
Measured: one year
Safety of bortezomib in renal transplant recipients
Infectious and non-infectious adverse events occurring during study in the two arms of treatment
Measured: one year
Patient and graft survival
Measured: one year
T and B lymphocytes subsets with bortezomib
Flow cytometry study of T and B lymphocytes subsets at inclusion, month-6 and month-12 in patients treated with bortezomib
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2014 (estimated)
- Study start11 Feb 2015
- Primary completion16 Jul 2020
- Study completion16 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Antibody-mediated Transplant RejectionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Fondation Centaure, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Christophe Legendre, MD, PhD, Study chair, Assistance Publique - Hôpitaux de ParisRenaud Snanoudj, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02201576
- Sponsor's protocol ID
- P120119
- Acronym
- TRIBUTE
- Status last verified
- Feb 2026
- First submitted
- 17 Jul 2014
- Last updated
- 13 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Snanoudj R, Marquant F, Renaudin K, Dubois V, Koenig A, Arzouk N, Caillard S, Giral M, Jalal Eddine A, Mazouz H, Kamar N, Pernin V, Matignon M, Ouali N, Anglicheau D, Elie C. Bortezomib in combination with standard-of-care for late active antibody-mediated rejection with de novo donor-specific antibodies after kidney transplantation: a multicenter randomized trial. Transpl Int. 2026 Sep 23;39:16702. doi: 10.3389/ti.2026.16702. eCollection 2026.
PubMed 42846119
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Chronic Active Antibody-mediated Rejection With Bortezomib in Kidney Transplantation
- ClinicalTrials.gov ID
- NCT02201576
- Acronym / sponsor ID
- TRIBUTE / P120119
- Keywords
- Chronic antibody-mediated rejection,, transplant rejection, kidney transplantation,, proteasome inhibitor,, anti-HLA antibodies,, immunosuppressive agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Fondation Centaure, URC-CIC Paris Descartes Necker Cochin
- Study start
- 11 Feb 2015 (actual)
- Primary completion
- 16 Jul 2020 (actual)
- Study completion
- 16 Jul 2020 (actual)
- First posted
- 28 Jul 2014 (estimated)
- 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.
The purpose of the study is to assess the efficacy of bortezomib, in association with steroids, plasma exchange, and polyclonal intravenous immunoglobulins, in the treatment of chronic antibody mediated rejection due to donor specific anti-HLA antibodies, in kidney transplant recipients
Detailed description
Chronic active antibody-mediated rejection (AMR) is considered as a main cause of late allograft losses in kidney transplant recipients. It is due to the occurrence of de novo donor-specific anti-HLA antibodies (DSA), i.e. antibodies synthetized by the recipient after transplantation against its transplant. There is currently to efficient treatment. The purpose of our study is to determine the efficacy of bortezomib, a proteasome inhibitor, in the treatment of chronic active antibody-mediated rejection, in association with steroids, plasma exchanges, and polyclonal intravenous immunoglobulins. Patients are recipients of a first or a second kidney transplant for more than 3 months. They display de novo DSA i.e. DSA not detected the day of transplantation and in pre-transplant sera.. They display signs of chronic active AMR on kidney biopsy i.e. a glomerulitis (g) + peritubular capillaritis (ptc) Banff score g+ptc ≥ 2, with or without severe chronic glomerulopathy (Banff score cg<3). Kidney biopsy may have been performed systematically or because of: :
- detection of de novo DSA ,
- and /or proteinuria (> 0.5 g/24h)
- and /or slow graft dysfunction protocol biopsy Primary endpoint is a combined endpoint one year after inclusion, consisting of the stabilization of histological lesions on a new kidney biopsy (delta g+ptc ≤1 and delta cg < 1) and a decrease in DSA mean fluorescence intensity > 50%.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bortezomib | Experimental | Drug: BortezomibFive plasma exchanges, two cycles of bortezomib + dexamethasone, 4 courses of polyclonal intravenous immunoglobulins |
| Control | Active comparator | Drug: Plasma exchanges and intravenous immunoglobulinsFive plasma exchanges, dexamethasone, 4 courses of polyclonal intravenous immunoglobulins |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- recipients of a first or a second kidney transplant for more than 3 months
- age over 18 years
- with de novo donor specific antibodies (DSA), i.e. antibodies not detected the day of transplantation and in pre-transplant sera
- with histological lesions of chronic active antibody-mediated rejection (glomerulitis + peritubular capillaritis banff score and chronic glomerulopathy (g+ptc ≥ 2) on a graft biopsy performed because of renal function deterioration, proteinuria, detection of de novo DSA, or on a systematic biopsy
- written informed consent
Key exclusion criteria (11 listed)
- patient with preformed DSA
- recipient of a 3rd or 4th kidney transplant
- recipient of a transplant combined with another not renal organ
- patient with a history of humoral acute rejection during the current transplantation
- estimated GFR below 20 ml/min/1,73m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibAlso: Velcade1. Five plasma exchanges +0.1 g/kg of intravenous immunoglobulins at the end of each course 2. two cycles of bortezomib (1.3 mg/m2 IV at day-1, day-4, day-8, day-11) + oral dexamethasone (20 mg po at day-1, day-4, day-8, day-11) 3. four courses of polyclonal intravenous immunoglobulins every three weeks (2g/kg, the first two courses are performed simultaneously with the two bortezomib cycles) | Drug | Bortezomib |
| Plasma exchanges and intravenous immunoglobulins1. Five plasma exchanges +0.1 g/kg of intravenous immunoglobulins at the end of each course 2. four courses of polyclonal intravenous immunoglobulins every three weeks (2g/kg) 3. oral dexamethasone (20 mg po at day-1, day-3, day-5, day-7 of the two first intravenous immunoglobulins courses) | Drug | Control |
Primary outcome
histological lesions of humoral rejection and immunodominant donor specific antibody
Time frame: one year
Between inclusion biopsy and end of study biopsy delta g+ptc ≤1 and delta cg < 1 (Banff score of glomerulitis (g) capillaritis (ptc) and chronic allograft glomerulopathy (cg) Between inclusion and end of study, decrease in mean fluorescence intensity (MFI) of the immunodominant donor specific anti-HLA antibody (DSA with the highest MFI) by Luminex greater than 50%
9 secondary outcomes
histological lesions of humoral rejection
Time frame: one year
immunodominant donor specific antibody
Time frame: one year
all donor specific antibodies at one year
Time frame: one year
all donor specific antibodies
Time frame: 6 months
Histological lesions
Time frame: one year
renal function and proteinuria
Time frame: one year
Safety of bortezomib in renal transplant recipients
Time frame: one year
Patient and graft survival
Time frame: one year
T and B lymphocytes subsets with bortezomib
Time frame: one year
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 13 Feb 2026.
- Derived from this study: PubMed 42846119Snanoudj R, Marquant F, Renaudin K, Dubois V, Koenig A, Arzouk N, Caillard S, Giral M, Jalal Eddine A, Mazouz H, Kamar N, Pernin V, Matignon M, Ouali N, Anglicheau D, Elie C. Bortezomib in combination with standard-of-care for late active antibody-mediated rejection with de novo donor-specific antibodies after kidney transplantation: a multicenter randomized trial. Transpl Int. 2026 Sep 23;39:16702. doi: 10.3389/ti.2026.16702. eCollection 2026.
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Posttransplant Diabetes Mellitus, Acute Graft Rejection
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.
Christophe Legendre, MD, PhD study chair
Assistance Publique - Hôpitaux de Paris
Renaud Snanoudj, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib and Plasma exchanges and intravenous immunoglobulins in people with Chronic Antibody-mediated Transplant Rejection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 10 inclusion and 11 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 13 Feb 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 France. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
histological lesions of humoral rejection and immunodominant donor specific antibody (time frame: one year). 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 NCT02201576, which also lists 1 linked publication.
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 13 Feb 2026; AzTrials last refreshed its copy on 7 Nov 2026.