Comparison Between Bortezomib and Rituximab Plus Plasmapheresis in AMR

Study Overview
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Brief Summary
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Chronic-active antibody-mediated rejection (cAMR) due to de novo or pre-formed donor specific antibody (DSA) is currently considered the main cause of long-term allograft losses.Based on the aim of reducing or eliminating DSA, some proposed different therapeutic regimens for cAMR treatment. All of these protocols were derived from previous experience using acute antibody-mediated rejection and desensitization protocols, and mainly consisted of steroids, plasma exchange (PE), IVIG and RTX in various modalities. More recently, bortezomib was also proposed.To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab with or without Bortezomib in chronic-active antibody-mediated rejection (cAMR) settings this study designed.

Detailed Description
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20 kidney transplant recipients (KTRs) with a diagnosis of cAMR in a prospective randomized clinical trial will be recruited in two arms : ten KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab (PE-IVIG-RTX group) vs 10 patients receiving the same therapy plus Bortezomib. Differences between transplanted kidney survival and functional outcomes 6 mo after diagnosis and histological features and donor-specific antibody (DSA) characteristics (MFI ) will be investigated between two arms.

Official Title
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Comparison Between Rituximab + PLX + IVIG With and Without Bortezomib in the Treatment of Antibody Mediated Kidney Transplanted Rejection

Conditions
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Antibody-mediated Rejection

Intervention / Treatment
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* Drug: Bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients presented with renal biopsy demonstrating ABMR in the absence of T-cell-mediated rejection Exclusion Criteria: Mixed AMR and T cell rejection do not sign the consent
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Plasmapheresis<br>5 Sessions Plasmapheresis and 100 mg/kg Intra venous immunoglobulin at the end of each session and one dose 375mg/m2 rituximab at the end of last session | |
| Active Comparator: Plasmapheresis plus Bortezomib<br>Drug 5 Sessions Plasmapheresis and 100 mg/kg Intra venous immunoglobulin at the end of each session and one dose 375ml/m2 rituximab at the end of last session plus bortezomib Injections 1.3mg/m2 intravenously on days 1, 4, 8, and 11 | Drug: Bortezomib<br>* one cycle of bortezomib (each cycle: 1.3mg/m2 intravenously on days 1, 4, 8, and 11)<br>* Other names: Velcade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| graft survival | Glomerular Filtration Rate | at month 6 following diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal functional tests | Serum Cr | at month 6 following diagnosis | 
| Changes in Grading of antibody mediated rejection regarding Banff criteria in pathology | kidney biopsy | at month 6 following diagnosis | 
| DSAs-MFI | Serum Test | at month 6 following diagnosis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transplantation, plasmapheresis