Randomized Trial of Induction Therapies in High Immunological Risk Kidney Transplant Recipients
Condition: Kidney Transplantation
Intervention: Rabbit Antithymocyte Globulin; Velcade; Rituxan
Intervention description: rATG will be given 1.5mg/kg intravenous (IV) per dose.; Velcade will be given 1.3mg/m2 via intravenous push (IVP) per dose.; Given via IV per group assignment.
Intervention MeSH terms: Rituximab; Bortezomib; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Kidney; Renal; Rejection; High risk; Induction; Immunology; Transplantation; B Cell; Allograft; Desensitization

Summary:

      The purpose of this research study is to find out the effects of adding B lymphocyte
      modulating agents in patients at risk for rejection receiving an anti-rejection
      (immunosuppressive) regimen of Thymoglobulin® induction with Prograf®, Cellcept® and
      corticosteroid therapy.
    

Eligibility criteria:

        Inclusion Criteria

        Each patient must meet all of the following inclusion criteria to be enrolled in the study:

          -  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             not part of normal medical care, with the understanding that consent may be withdrawn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.

          -  Patient is between the 18 and 65 years of age, inclusive.

          -  Patient is considered high risk for acute rejection based on any one of the following:

               -  Patient has a current Cytotoxic PRA≥ 20% or a peak Cytotoxic PRA ≥50%

               -  Patient has a T or B-cell positive crossmatch (by flow cytometry) with confirmed
                  donor-specific antibodies on solid-phase assay.

               -  Historical positive serologic or cytotoxic crossmatch or DSA to donor

               -  Prior allograft loss with a history of more than one acute rejection episode.

          -  Female subject is either postmenopausal for at least 1 year prior to initiation of
             study treatment, is surgically sterilized, or if of childbearing potential, agrees 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 agrees to
             completely abstain from heterosexual intercourse. Women of childbearing potential must
             have a negative serum pregnancy test within the last 48 hours prior to receiving study
             medication.

          -  Male subjects, even if surgically sterilized (i.e. status post-vasectomy) 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.

          -  Patient must have no known contraindications to treatment with bortezomib, rituximab,
             or thymoglobulin.

        Exclusion Criteria

          -  Patients that have previously received or are receiving an organ transplant other than
             kidney.

          -  Patient who lost a previous allograft due to recurrence of disease

          -  Patient is receiving a HLA identical living related kidney transplant

          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             or polyclonal antibodies

          -  Patients with an absolute neutrophil count of < 1,000/mm3 or platelet count <
             100,000/mm3within 30 days of consent.

          -  Patient has Grade 2 peripheral neuropathy by CTCAE criteria 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 (see section 9.3), uncontrolled
             angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
             of acute ischemia or active conduction system abnormalities. Prior to study entry, any
             abnormality on ECG performed within 30 days of consent has to be documented by the
             investigator or the patient's transplant nephrologist as not medically relevant.

          -  Patients who are anti-HIV-positive, or HBsAg-positive or Anti-HCV positive on testing
             performed within one year of consent.

          -  Diagnosed or treated for 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.

          -  Patients with current or recent severe systemic infections within the 2 weeks prior to
             initiation of study treatment.

          -  Receipt of a live vaccine within 4 weeks prior to initiation of study treatment.

          -  Use of other investigational drugs within 30 days or 5 half-lives prior to initiation
             of study treatment, whichever is longer

          -  Evidence of severe liver disease by medical history or physical exam with abnormal
             liver profile (aspartate aminotransferase [AST], alanine aminotransferase [ALT] or
             total bilirubin > 1.5 times upper limit of normal [ULN]) on testing performed within
             30 days of consent.

          -  Pregnant or nursing (lactating) women and women who might become pregnant during the
             study. Female subject is pregnant or breast-feeding. Confirmation that the subject is
             not pregnant must be established by a negative serum -human chorionic gonadotropin
             pregnancy test result within the last 48 hours prior to receiving study medication.
             Pregnancy testing is not required for post-menopausal or surgically sterilized women.

          -  EBV serologic mismatch (i.e. EBV+ donor transplanted to EBV- recipient)

          -  CMV serologic mismatch (i.e. CMV+ donor transplanted to CMV- recipient)