Impact of Proteasome Inhibition on Anti-Donor HLA Antibody Production After Kidney Transplantation

NCT01349595 | Terminated Phase 2 Results DMC

• 1 other identifier: 10-001487
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if treating patients who have high levels of donor specific alloantibodies post-transplant with bortezomib might prevent the development of transplant glomerulopathy and preserve allograft function.

Conditions

Disorder of Transplanted Kidney

Outcome Measures

Primary Outcomes (1)

• The Incidence of a Combined Endpoint of Death-censored Graft Loss or Greater Than 50% Reduction in Estimated Glomerular Filtration (eGFR) in Study Subjects.

  60 months after enrollment in the study

Study Arms (2)

Bortezomib

EXPERIMENTAL

Bortezomib is a type of targeted chemotherapy

Drug: Bortezomib

Standard Post-transplant Treatment

NO INTERVENTION

Mayo Clinic standard post kidney transplant follow-up.

Interventions

Bortezomib DRUG

Patients randomized to bortezomib treatment will receive 2, 4-dose cycles of drug followed by a 2 month "hiatus". At the end of this time, subjects will be re-evaluated for the appropriateness of receiving a 3rd and 4th cycle of bortezomib. Bortezomib will be given subcutaneously (under the skin). If unable to give subcutaneously, bortezomib will be given as a single IV (injection into vein) over a time of 3 to 5 seconds. Patients will receive up to 4, four-dose cycles of 1.3 mg/m(2) (based on body surface area).

Also known as: Velcade

Bortezomib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female subject is either postmenopausal for at least 1 year before the screening visit, surgically sterilized, or if they are of childbearing potential agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse.
• Male subjects, even if surgically sterilized (i.e. status postvasectomy), must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug or completely abstain from heterosexual intercourse.
• Kidney transplant recipients (living and deceased donors) who received a transplant in the last 3 years and have high Donor Specific Antibody (DSA) levels (defined as Mean Fluorescent Intensity levels \>2000 by solid phase and single antigen bead LABscreen assays).

You may not qualify if:

• Patients who are recipients of ABO (blood type) incompatible kidney transplants.
• Patient with an Glomerular Filtration Rate (eGFR) ≤30 m/min at time of study entry.
• Patient with biopsy proven transplant glomerulopathy (Banff 2007 - cg score ≥2) within 2 months prior to randomization.
• Patients with biopsy-proven acute rejection at the time of randomization defined as Acute Cellular Rejection Patients with documented biopsy proven recurrence of disease or de novo glomerular disease post-transplant prior to enrollment.
• Patient has a platelet count of \<30 x 10(9)/L within 14 days before enrollment.
• Patient has an absolute neutrophil count of \<1.0 x 10(9)/L within 14 days before enrollment.
• Patient has a history of post-transplant neutropenia on mycophenolate based immunosuppressive therapy.
• Evidence of severe liver disease with abnormal liver profile (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] \>3 times upper limit of normal \[ULN\]) at screening.
• Patient has \>1.5 x ULN Total Bilirubin.
• Patient had any history of myocardial infarction in the past 3 years prior to enrollment or has New York Heart Association (NYHA) Class II to IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
• Patient has hypersensitivity to bortezomib, boron, or mannitol.
• Female subject is pregnant or lactating.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Cytomegalovirus (CMV) sero-negative recipients who received a transplant from a CMV-sero-positive donor.(CMV- recipients of CMV- donor kidneys are acceptable)
• Epstein Barr Virus (EBV) sero-negative recipients.

Sponsors & Collaborators

• Mark Stegall: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Bortezomib

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Although subjects completed the cycles of drug, long term follow-up visits were not possible due to funding discontinuation.

Results Point of Contact

• Title: Dr. Mark Stegall
• Organization: Mayo Clinic

Stegall.Mark@mayo.edu

507-266-2812

Study Officials

• Mark Stegall, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: May 5, 2011
• First Posted: May 6, 2011
• Study Start: December 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: October 28, 2015
• Results First Posted: September 9, 2015

Record last verified: 2015-10

Locations

US (1)