Bortezomib in Rejection of Kidney Transplants (TRIBUTE)

February 11, 2026 updated by: Assistance Publique - Hôpitaux de Paris

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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: :

  1. detection of de novo DSA ,
  2. and /or proteinuria (> 0.5 g/24h)
  3. 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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75015
        • Hopital Necker Enfants-malades

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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:

    • 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.

Exclusion Criteria:

  • 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)
  • 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
  • inclusion in another clinical therapeutic trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Bortezomib
Five plasma exchanges, two cycles of bortezomib + dexamethasone, 4 courses of polyclonal intravenous immunoglobulins
Drug: Bortezomib
  1. 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)
Other Names:
  • Velcade
Active Comparator: Control
Five plasma exchanges, dexamethasone, 4 courses of polyclonal intravenous immunoglobulins
Drug: Plasma exchanges and intravenous immunoglobulins
  1. 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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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%
one year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
histological lesions of humoral rejection
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)
one year
immunodominant donor specific antibody
Time Frame: one year
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%
one year
all donor specific antibodies at one year
Time Frame: one year
Between inclusion and end of study, variation of the title of each DSA and the sum of the DSAs
one year
all donor specific antibodies
Time Frame: 6 months
Between inclusion and month-6, evolution in mean fluorescence intensity (MFI) of all donor specific anti-HLA antibodies by Luminex
6 months
Histological lesions
Time Frame: one year
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)
one year
renal function and proteinuria
Time Frame: one year
Evolution between inclusion and end of study at one-year of serum creatinine, estimated GFR (MDRD formula), proteinuria output, proteinuria/creatinuria ratio
one year
Safety of bortezomib in renal transplant recipients
Time Frame: one year
Infectious and non-infectious adverse events occurring during study in the two arms of treatment
one year
Patient and graft survival
Time Frame: one year
one year
T and B lymphocytes subsets with bortezomib
Time Frame: one year
Flow cytometry study of T and B lymphocytes subsets at inclusion, month-6 and month-12 in patients treated with bortezomib
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
URC-CIC Paris Descartes Necker Cochin
Fondation Centaure

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Christophe Legendre, MD, PhD, Assistance Publique - Hôpitaux de Paris
  • Principal Investigator: Renaud Snanoudj, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 11, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 16, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 16, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 17, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 28, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 11, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P120119

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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