Clinical trial NCT05345717: Novel Desensitization Kidney Transplantation
Official title: Novel Desensitization Protocol With Proteasome Inhibitor and Costimulation Blockade for Highly Sensitized Patients to Allow for Successful Kidney Transplantation. A Pilot Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Kidney Transplantation
End Stage Kidney Disease (ESRD)
Keywords: kidney transplantation
sensitized patients
belatacept
proteasome inhibitor
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2022-04-26
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A pilot study on 5 subjects
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Likelihood of finding a donor to whom the study participant does not have strong anti-donor HLA specific antibodies (DSA).
timeFrame: 1 year
Secondary outcomes:
measure: Strong Human Leukocyte Antigen (HLA) antibodies with mean fluorescence intensity (MFI) reduced by more than 50%
timeFrame: 1 year
measure: Time to transplant
timeFrame: 1 year
measure: Episodes of Antibody Mediated Rejection (AMR) and Acute Cellular Rejection (ACR)
timeFrame: 1 year
measure: Death
timeFrame: 1 year
measure: Serious infection requiring inpatient intravenous therapies
timeFrame: 1 year
measure: Post-transplant lymphoproliferative disorder
timeFrame: 1 year
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Piotr Witkowski, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: