Desensitization Protocol for Highly Sensitized Patients on the Waiting List for Kidney Transplant

Study Overview
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Brief Summary
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The purpose of this study is to determine whether high dose IVIG and B cell depleting agents can be used effectively in highly sensitized wait-listed patients.

Detailed Description
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HLA sensitization is known to be the most important barrier to deceased donor kidney allocation. Therefore, the investigators need to develop better strategies for managing pre-sensitized patients using desensitization protocol. In this study the investigators will used two kinds of medication for the reduction of circulating antibodies (high dose IVIg, B cell depleting agents) to highly-sensitized patients who are on the waiting list for a deceased donor kidney transplantation. After desensitization, the investigators will check that this treatment can increase their chances of receiving a kidney transplant.

Official Title
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Phase 2 Study of Desensitization Protocol for Highly Sensitized Wait Listed Patients

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: High dose IVIG and B cell depleting agents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 patients who are on the waiting list more than 4 years PRA I or II > 50% Exclusion Criteria: Recent recipients of any live attenuated vaccine(s) within 4 weeks Subjects who have received IVIG or B cell depleting agents previously Subjects with positive result for viral hepatitis(B,C) or HIV infection Subjects with active infection Lactating or pregnant females Subjects who have history of malignancy in recent 5years Subjects who have experience of treatment for the psychiatric problem in recent 6months Subjects who have hematologic abnormality (Hb < 7g/dL, Platelet < 100,000/mm3, AST/ALT > 80IU)

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Group 1<br>This group will not receive IVIG and B cell depleting agents | |
| Experimental: Group 2<br>This group will receive IVIG and B cell depleting agents | Drug: High dose IVIG and B cell depleting agents<br>* IVIG(2g/kg two times on day 1, 30) Rituximab(375mg/m2 on day 3) Bortezomib(1.3mg/m2 four times on day 31, 34, 38, 41)<br>* Other names: Velcade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rates of kidney transplantation |  | from one to five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in anti-HLA alloantibodies |  | 1year | 
| Renal allograft survival | graft and patient survival | from one to five year | 
| The number of serious complication |  | from one to five year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Waiting list, Deceased donor kidney transplantation, Desensitization, anti HLA antibody