Bortezomib With Steroid Pulse Therapy for Acute Cellular Rejection in Kidney Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to determine whether bortezomib is effective in the treatment of acute cellular rejection after kidney transplantation.

Detailed Description
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When acute cellular rejection occurred in kidney allograft, investigators administer high dose steroid. However, there is insufficient effect in about 20-30%. Bortezomib acts not only on plasma cells, but also T cells, B cells and dendritic cells. In addition, bortezomib is relatively safe drug compared to thymoglobulin which investigators use in the cases of steroid failure. Therefore, investigators administer bortezomib with steroid in one group, and compared the group with the other group in which conventional steroid treatment is done.

Official Title
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Bortezomib With Steroid Pulse Therapy for Acute Cellular Rejection in Kidney

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Steroid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: living donor kidney transplantation recipients patients who were performed kidney biopsies because of laboratory and clinically suspected rejection Biopsy proven acute cellular rejection (Banff I - IIA) with C4d negative Single luminex panel reactive antibody (PRA) I & II mean fluorescent intensity (MFI) < 3000 Exclusion Criteria: patients who received other major organ transplantation combined with urinary tract infection or obstruction combined with acute antibody mediated rejection poor compliance

Ages Eligible for Study
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Minimum Age: 19 Years

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bortezomib<br>Bortezomib (subcutaneous) 1.3mg/m2 on day 1, 4 and 7 with Steroid - Methylprednisolone (intravenous) Day 1 - 7: 500 mg/500 mg/500 mg/250 mg/250 mg/125 mg/125 mg After day 7: prednisolone (oral) 30 - 60 mg, then taper the dosage | Drug: Bortezomib<br>* In one group, investigators administer bortezomib and steroid to manage acute cellular rejection in kidney transplantation, and compare the results with another group in which only steroid was administered.<br>* Other names: Velcade;Drug: Steroid<br>* Investigators administer steroid in both groups for conventional treatment of acute cellular rejection.<br>|
| Active Comparator: Steroid<br>Steroid - Methylprednisolone (intravenous) Day 1 - 7: 500 mg/500 mg/500 mg/250 mg/250 mg/125 mg/125 mg After day 7: prednisolone (oral) 30 - 60 mg, then taper the dosage | Drug: Steroid<br>* Investigators administer steroid in both groups for conventional treatment of acute cellular rejection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum creatinine | Investigators measure patients' serum creatinine at day 14. | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of steroid failure | Steroid failure is defined as serum creatinine at day 8 ≥ serum creatinine at day 0. | Day 7 | 
| Serum creatinine | Investigators measure patients' serum creatinine at month 1. | Month 1 | 
| Infection | Infection as measured by clinical, laboratory and microbiological data | Until 1 year after intervention | 
| Recurrence of Rejection | Recurrence of rejection as measured by clinical and laboratory data with graft biopsy. | Until 1 year after intervention |