The Impact of Velcade(TM)on Antibody Secreting Cells in Sensitized Renal Allograft Candidates

This study has been completed.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Mark Stegall, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00722722
First received: July 23, 2008
Last updated: April 28, 2016
Last verified: April 2016
  Purpose
Patients planning to have kidney transplantation who are sensitized to their donors have high levels of donor specific alloantibodies. High levels of donor specific antibodies put kidney transplant recipients at risk for rejection very early after transplant. This study is trying to determine if the drug bortezomib (Velcade ™) can reduce donor specific alloantibodies to a level that permits kidney transplantation without a high risk for rejection.

Condition Intervention Phase
Kidney Transplantation
Drug: Bortezomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Impact of Velcade(TM)on Antibody Secreting Cells in Sensitized Renal Allograft Candidates

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Response to Bortezomib Monotherapy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Response to treatment with Bortezomib (BTZ) alone was defined as a reduction in serum Donor Specific Alloantibody (DSA) levels following treatment. DSA levels were measured prior to treatment and after treatment. A good response occurred if all DSA were reduced. A partial response when a reduction was observed in at least one DSA, but not all DSA. No response occurred when no reduction of any DSA was attained.


Enrollment: 18
Study Start Date: June 2008
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 4 dose group
4 doses of bortezomib (1.3mg/m^2 of body surface area)
Drug: Bortezomib
Velcade given in four-dose cycles intravenously (through a vein).
Other Name: Velcade(TM)
Active Comparator: 16 dose group
16 doses of bortezomib (1.3mg/m^2 of body surface area)
Drug: Bortezomib
Velcade given in four-dose cycles intravenously (through a vein).
Other Name: Velcade(TM)
Active Comparator: 32 dose group
32 doses of bortezomib (1.3mg/m^2 of body surface area)
Drug: Bortezomib
Velcade given in four-dose cycles intravenously (through a vein).
Other Name: Velcade(TM)

Detailed Description:
The study is designed to assess the impact of in vivo treatment of bortezomib on anti-human leukocyte antigen (HLA) production by normal antibody secreting cells (ASC) in sensitized renal allograft candidates. The design involves treatment of subjects with bortezomib using one of three dosing regimens (4 doses, 16 doses or 32 doses of bortezomib). Using novel assays, anti-HLA production is determined by measuring the bone marrow derived ASC at baseline (prior to therapy) and after treatment (at day 14, 3 days after the last bortezomib dose). Paired data are used with patients serving as their own controls. Finally, the safety of bortezomib is evaluated by monitoring total serum antibody levels and the incidence of side effects (primarily neuropathy) at 1 month, the final follow-up point.
  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 post-menopausal, surgically sterilized, or she and/or sexual partner are willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
    • Male subject agrees to use an acceptable method for contraception for the duration of the study.
    • Renal transplant candidates who otherwise meet our acceptance criteria.
    • Evidence of alloantibody in their serum (panel reactive antibody >20% and specificities determined by single antigen flow bead assay).
    • Sensitized patients with no living donors or have donor-specific antibody levels too high to undergo successful transplantation using our current protocols (T or B cell crossmatch channel shift >500).

Exclusion Criteria:

  • Patient has a platelet count of <30 x 10^9/L within 14 days before enrollment.

    • Patient has an absolute neutrophil count (ANC) of <1.0 x 10^9/L within 14 days before enrollment.
    • Patient has >Grade 2 peripheral neuropathy within 14 days before enrollment.
    • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or 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 electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator as not medically relevant.
    • Patient has hypersensitivity to bortezomib, boron or mannitol.
    • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
    • Patient has received other investigational drugs within14 days before enrollment.
    • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
    • Diagnosed or treated for malignancy within 5 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.
    • Contraindication to kidney transplantation—active infection, comorbid medical conditions, etc.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00722722

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Mark D. Stegall, M.D. Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Mark Stegall, PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00722722     History of Changes
Other Study ID Numbers: 08-000556 
Study First Received: July 23, 2008
Results First Received: April 21, 2015
Last Updated: April 28, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Bortezomib
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 22, 2016