Novel Desensitization Kidney Transplantation

Study Overview
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Brief Summary
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This proposal's objective is to determine whether belatacept, in conjunction with a proteasome inhibitor can be used to safely increase the likelihood of finding an acceptable donor for highly HLA sensitized kidney transplant candidates.

Detailed Description
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This is a pilot study to test the safety and effectiveness of the desensitization therapy with belatacept and proteasome inhibitor to increase the likelihood of of finding an acceptable donor for highly HLA sensitized kidney transplant candidates.

Official Title
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Novel Desensitization Protocol With Proteasome Inhibitor and Costimulation Blockade for Highly Sensitized Patients to Allow for Successful Kidney Transplantation. A Pilot Study.

Conditions
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Kidney Transplantation, End Stage Kidney Disease (ESRD)

Intervention / Treatment
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* Drug: Belatacept Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Highly sensitized patient cPRA 99-100% AND actively listed for kidney transplantation at the kidney transplantation Program at University fo Chicago Ebstein Barr Virus (EBV) Immunoglobulins (IgG) seropositive No active systemic infection No allergy to proteasome inhibitors (Bortezomib), or to belatacept No known malignancy in the previous 2 years except for non-melanomatous skin cancer Female who agrees to practice 2 effective methods of contraception through 3 months after the last dose of Bortezomib Patient vaccinated against hepatitis B virus with positive level of HBsAb Patients fully vaccinated against Coronavirus Disease 2019 at least 2 weeks prior to the start of the 1st cycle. Actively listed for kidney transplant at the Transplant Institute at University of Chicago Exclusion Criteria: Patient with significant neuropathy by the Common Terminology Criteria for Adverse Events (CTCAE) criteria within 14 days before enrollment (Grades 3-4 or Grade 2 with pain) Myocardial infarction within 6 months of enrollment or has Heart Failure in acute dialysis quality initiative (ADQI) ESRD classification system Class 2 non restrictive (2NR) or greater, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia or active conduction system abnormalities Patient who received other investigational drugs within 14 days prior to initiation of study treatment Receipt of a live vaccine within 4 weeks prior to initiation of study treatment Evidence of severe liver disease by history or physical exam or with abnormal liver profile ( > 1.5 times upper limit of normal within 30 days of consent) Female who is breast feeding or pregnant Untreated latent tuberculosis History of Post Transplant Lymphoproliferative Disease (PTLD) Patient still carrying previous kidney transplant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Interventional Model Description: A pilot study on 5 subjects
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients treated with belatacept and proteasome inhibitor<br>Highly sensitized patients will be treated with belatacept and proteasome inhibitor and monitored for decreasing calculated Panel of Reactive Antibodies (cPRA) and suitable kidney donor base don negative crossmatch | Drug: Belatacept Injection<br>* Patient will initiate belatacept therapy and will received 2 cycles of proteasome inhibitor therapy<br>* Other names: proteasome inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Likelihood of finding a donor to whom the study participant does not have strong anti-donor HLA specific antibodies (DSA). | The likelihood of finding a suitable donor will calculated base on calculated Panel of Reactive Antibodies measured 1month after the therapy | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Strong Human Leukocyte Antigen (HLA) antibodies with mean fluorescence intensity (MFI) reduced by more than 50% | A number of strong HLA antibodies with MFI reduced by more than 50% will be counted | 1 year | 
| Time to transplant | Time from the beginning of the implementation of the therapy to kidney transplantation will be measured | 1 year | 
| Episodes of Antibody Mediated Rejection (AMR) and Acute Cellular Rejection (ACR) | Number of episodes of AMR and ACR after kidney transplantation will be counted | 1 year | 
| Death | The incidence of episodes of patient death will be calculated | 1 year | 
| Serious infection requiring inpatient intravenous therapies | Incidence rate of the episodes of serious infection requiring inpatient intravenous therapies will be calculated during the study | 1 year | 
| Post-transplant lymphoproliferative disorder | The incidence rate of the episodes of post-transplant lymphoproliferative disorder will be calculated | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney transplantation, sensitized patients, belatacept, proteasome inhibitor