Novel Desensitization Kidney Transplantation

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05345717
• Other study ID #: IRB21-0323
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 1, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2023
• Source: University of Chicago
• Contact: Piotr Witkowski, M.D. Ph.D.
• Phone: 773 702 2447
• Email: pwitkowski[@]surgery.bs.uchicago.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5
• Est. completion date: December 31, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Diseases
• Kidney Failure, Chronic
• Kidney Transplantation

Intervention

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

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Time to transplant	Time from the beginning of the implementation of the therapy to kidney transplantation will be measured	1 year
Secondary	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
Secondary	Death	The incidence of episodes of patient death will be calculated	1 year
Secondary	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
Secondary	Post-transplant lymphoproliferative disorder	The incidence rate of the episodes of post-transplant lymphoproliferative disorder will be calculated	1 year