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

This study is currently recruiting participants.
Verified January 2013 by Mayo Clinic
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01349595
First received: May 5, 2011
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to see if the study drug bortezomib will prevent transplant glomerulopathy in patients who are at a high risk of developing the condition due to high donor-specific alloantibody in post kidney transplant recipients.


Condition Intervention Phase
Disorder of Transplanted Kidney
Donor Specific Alloantibodies
Drug: Bortezomib
Other: Standard posttransplant treatment
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Impact of Proteasome Inhibition on Anti-Donor HLA Antibody Production After Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Incidence of transplant glomerulopathy. [ Time Frame: 3 years posttransplant ] [ Designated as safety issue: No ]
    Incidence of transplant glomerulopathy at 3 years after transplantation in recipients who were identified to have anti-donor HLA antibodies (donor specific alloantibodies, DSA) in their serum in the first two years after kidney transplantation.


Estimated Enrollment: 60
Study Start Date: December 2011
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib dosing Drug: Bortezomib
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 as a single IV push over a time of 3 to 5 seconds. Patients will receive up to 4, four-dose cycles of 1.3 mg/m2 (based on body surface area).
Active Comparator: Standard Posttransplant Treatment Other: Standard posttransplant treatment
Mayo Clinic protocolized post kidney transplant follow-up.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Female subject is either postmenopausal for at least 1 year before the screening visit, is 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 have high DSA levels (defined as MFI levels >2000 by solid phase and single antigen bead LABscreen assays) at any of the early post-transplant protocol time points (4, 12, 24 months after transplant) and who do not have TG on protocol biopsy at the same time point. To verify the DSA level, the subject must have a DSA with MFI>2000 on 2 sequential measurements within 1 month of each other.

Exclusion Criteria:

  • Patient has a platelet count of < 30 x 109/L within 14 days before enrollment.
  • Patient has an absolute neutrophil count of < 1.0 x 109/L within 14 days before enrollment.
  • Patient has > 1.5 x ULN Total Bilirubin
  • Patient has > or equal Grade 2 peripheral neuropathy
  • Patient had any history of myocardial infarction prior to enrollment or has New York Heart Association (NYHA) Class I to IV heart failure (see Appendix 8.4), 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. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for postmenopausal or surgically sterilized women.
  • Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on Day 1 before first dose of study drug, if applicable.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
  • Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
  • Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
  • Renal transplant patients who already have TG on their protocol biopsy.
  • Active infection.
  • Inability to perform follow-up or to undergo protocol biopsy.
  • Diabetic neuropathy
  • Other current or past history of neuropathy
  • Patient who is CMV or EBV negative
  • Patients with BK viremia (peripheral blood viral load of 5000 to 5,000,000 copies/mL)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01349595

Contacts
Contact: Nong Yowe Braaten, LPN 507-538-9617 braaten.nong@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Nong Yowe Braaten, LPN    507-538-9617    braaten.nong@mayo.edu   
Principal Investigator: Mark Stegall, MD         
Sponsors and Collaborators
Mayo Clinic
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Mark Stegall, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Mark Stegall, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01349595     History of Changes
Other Study ID Numbers: 10-001487
Study First Received: May 5, 2011
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 14, 2014