Ixazomib for Desensitization
Condition: Kidney Diseases; End Stage Renal Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic
Intervention: Ixazomib Oral Capsule
Intervention description: Highly sensitized kidney transplant candidates on the waitlist for more than 24 months will receive ixazomib 3 mg (and dexamethasone 20 mg) on days 1, 8, and 15 of a 28 cycle. Patients will take ixazomib and dexamethasone for twelve (12) 28-day cycles.
Intervention MeSH terms: Ixazomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this research study is to find out how well ixazomib (the study drug) works to
      desensitize highly sensitized kidney transplant recipients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients 18-70 years of age.

          -  Able to provide informed consent.

          -  Female patients who are postmenopausal for at least 1 year before the screening visit,
             or are surgically sterile, or If they are of childbearing potential, agree to practice
             2 effective methods of contraception, at the same time, from the time of signing the
             informed consent form through 30 days after the last dose of study drug, OR agree to
             practice true abstinence when this is in line with the preferred and usual lifestyle
             of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal,
             post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

          -  Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree
             to one of the following: Agree to practice effective barrier contraception during the
             entire study treatment period and through 30 days after the last dose of study drug,
             or Agree to practice true abstinence when this is in line with the preferred and usual
             lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation,
             symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of
             contraception.)

          -  Patients must be highly sensitized with a cPRA ≥ 80%

          -  Be active on the waitlist for kidney transplantation > 24 months to confirm their
             inability to receive a deceased donor transplant because of their sensitization
             status.

          -  Patients must meet the following clinical laboratory criteria:

               1. Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3.
                  Platelet transfusions to help patients meet eligibility criteria are not allowed
                  within 3 days before study enrollment.

               2. Hemoglobin higher than 6 g/dL

               3. Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN).

               4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.

        Exclusion Criteria:

          -  Female patients who are lactating or have a positive serum pregnancy test during the
             screening period

          -  Major surgery requiring hospitalization within 6 months before enrollment

          -  Infection requiring systemic antibiotic therapy or other serious infection within 14
             days before study enrollment

          -  Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
             hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,
             unstable angina, or myocardial infarction within the past 6 months

          -  Systemic treatment, within 14 days before the first dose of ixazomib, with strong
             CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin,
             phenobarbital), or use of St. John's wort

          -  Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol

          -  Inability to take oral medication

          -  Diagnosed or treated for another malignancy within 2 years before study enrollment or
             previously diagnosed with another malignancy and have any evidence of residual
             disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are
             not excluded if they have undergone complete resection

          -  Grade 2 or greater peripheral neuropathy according to NCI Common Terminology Criteria
             for Adverse Events (CTCAE)

          -  Participation in other interventional clinical trials, including those with other
             investigational agents not included in this trial, within 6 months of the start of
             this trial and throughout the duration of this trial

          -  Patients that have previously been treated with ixazomib, or participated in a study
             with ixazomib whether treated with ixazomib or not

          -  Active or treated infection for HIV, HCV or HBV

          -  History of Liver cirrhosis, biopsy confirmed

          -  Elevated transaminases (greater than 3 times the upper limit of normal)

          -  Known hypersensitivity to ixazomib

          -  Active substance abuse by self-report or medical record