Bortezomib in Rejection of Kidney Transplants

NCT02201576 | Completed Phase 2 DMC

• 1 other identifier: P120119
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Chronic Antibody-mediated Transplant Rejection

Keywords

Chronic antibody-mediated rejection,; transplant rejection, kidney transplantation,; proteasome inhibitor,; anti-HLA antibodies,; immunosuppressive agents

Outcome Measures

Primary Outcomes (1)

• 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%

  one year

Secondary Outcomes (9)

• histological lesions of humoral rejection

  one year

• immunodominant donor specific antibody

  one year

• all donor specific antibodies at one year

  one year

• all donor specific antibodies

  6 months

• Histological lesions

  one year

Study Arms (2)

Bortezomib

EXPERIMENTAL

Five plasma exchanges, two cycles of bortezomib + dexamethasone, 4 courses of polyclonal intravenous immunoglobulins

Drug: Bortezomib

Control

ACTIVE COMPARATOR

Five plasma exchanges, dexamethasone, 4 courses of polyclonal intravenous immunoglobulins

Drug: Plasma exchanges and intravenous immunoglobulins

Interventions

Bortezomib DRUG

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)

Also known as: Velcade

Bortezomib

Plasma exchanges and intravenous immunoglobulins DRUG

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)

Control

Eligibility Criteria

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

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• URC-CIC Paris Descartes Necker Cochin: collaborator
• Assistance Publique - Hôpitaux de Paris: lead
• Fondation Centaure: collaborator

Study Sites (1)

Hopital Necker Enfants-malades

Paris, 75015, France

Location

MeSH Terms

Interventions

Bortezomib; Plasma Exchange; Immunoglobulins, Intravenous

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christophe Legendre, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

• Renaud Snanoudj, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2014
• First Posted: July 28, 2014
• Study Start: February 11, 2015
• Primary Completion: July 16, 2020
• Study Completion: July 16, 2020
• Last Updated: February 13, 2026

Record last verified: 2026-02

Locations

FR (1)