Back to results

Novel Desensitization Kidney Transplantation

Primary Purpose

Kidney Transplantation, End Stage Kidney Disease (ESRD)

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Belatacept Injection

About this trial

This is an interventional treatment trial for Kidney Transplantation focused on measuring kidney transplantation, sensitized patients, belatacept, proteasome inhibitor

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of ChicagoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients treated with belatacept and proteasome inhibitor

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Time to transplant

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)

Number of episodes of AMR and ACR after kidney transplantation will be counted

Death

The incidence of episodes of patient death will be calculated

Serious infection requiring inpatient intravenous therapies

Incidence rate of the episodes of serious infection requiring inpatient intravenous therapies will be calculated during the study

Post-transplant lymphoproliferative disorder

The incidence rate of the episodes of post-transplant lymphoproliferative disorder will be calculated

Full Information

NCT ID

NCT05345717

First Posted

December 3, 2021

Last Updated

June 1, 2023

Sponsor

University of Chicago

1. Study Identification

Unique Protocol Identification Number

NCT05345717

Brief Title

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

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 1, 2022 (Actual)

Primary Completion Date

May 1, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Chicago

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Kidney Transplantation, End Stage Kidney Disease (ESRD)

Keywords

kidney transplantation, sensitized patients, belatacept, proteasome inhibitor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Model Description

A pilot study on 5 subjects

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Patients treated with belatacept and proteasome inhibitor

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Belatacept Injection

Other Intervention Name(s)

proteasome inhibitor

Intervention Description

Patient will initiate belatacept therapy and will received 2 cycles of proteasome inhibitor therapy

Primary Outcome Measure Information:

Title

Likelihood of finding a donor to whom the study participant does not have strong anti-donor HLA specific antibodies (DSA).

Description

The likelihood of finding a suitable donor will calculated base on calculated Panel of Reactive Antibodies measured 1month after the therapy

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Strong Human Leukocyte Antigen (HLA) antibodies with mean fluorescence intensity (MFI) reduced by more than 50%

Description

A number of strong HLA antibodies with MFI reduced by more than 50% will be counted

Time Frame

1 year

Title

Time to transplant

Description

Time from the beginning of the implementation of the therapy to kidney transplantation will be measured

Time Frame

1 year

Title

Episodes of Antibody Mediated Rejection (AMR) and Acute Cellular Rejection (ACR)

Description

Number of episodes of AMR and ACR after kidney transplantation will be counted

Time Frame

1 year

Title

Death

Description

The incidence of episodes of patient death will be calculated

Time Frame

1 year

Title

Serious infection requiring inpatient intravenous therapies

Description

Incidence rate of the episodes of serious infection requiring inpatient intravenous therapies will be calculated during the study

Time Frame

1 year

Title

Post-transplant lymphoproliferative disorder

Description

The incidence rate of the episodes of post-transplant lymphoproliferative disorder will be calculated

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Piotr Witkowski, M.D. Ph.D.

Phone

773 702 2447

pwitkowski@surgery.bs.uchicago.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Lindsay Basto, MSN RN

Phone

7737022504

Lindsay.Basto@uchospitals.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Piotr Witkowski, MD PhD

Organizational Affiliation

University of Chicago

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Piotr Witkowski, MD PhD

Phone

773-702-2447

pwitkowski@surgery.bs.uchicago.edu

12. IPD Sharing Statement

Learn more about this trial

Novel Desensitization Kidney Transplantation

We'll reach out to this number within 24 hrs