The Impact of Velcade(TM)on Antibody Secreting Cells in Sensitized Renal Allograft Candidates
Condition: Kidney Transplantation
Intervention: Bortezomib
Intervention description: Velcade given in four-dose cycles intravenously (through a vein).
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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             not part of normal medical care, with the understanding that consent may be withdrawn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.