Novel Desensitization Kidney Transplantation

Overview

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.

Full Title of Study: “Novel Desensitization Protocol With Proteasome Inhibitor and Costimulation Blockade for Highly Sensitized Patients to Allow for Successful Kidney Transplantation. A Pilot Study.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 1, 2024

Detailed Description

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.

Interventions

  • Drug: Belatacept Injection
    • Patient will initiate belatacept therapy and will received 2 cycles of proteasome inhibitor therapy

Arms, Groups and Cohorts

  • Experimental: Patients treated with belatacept and proteasome inhibitor
    • 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

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Chicago
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Piotr Witkowski, MD PhD, Principal Investigator, University of Chicago
  • Overall Contact(s)
    • Piotr Witkowski, M.D. Ph.D., 773 702 2447, pwitkowski@surgery.bs.uchicago.edu

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