Safety and Efficacy of Desensitization Therapy in Sensitized Participants Awaiting Heart Transplantation
Condition: Primary Heart Transplant; Heart Transplantation; Heart Transplant
Intervention: bortezomib; plasmapheresis
Intervention description: Bortezomib dosed at 1.3 mg/m^2 as a 3 to 5 second bolus administered by intravenous injection on treatment days 0, 3, 7 and 10. The first dose of bortezomib is administered between 4-8 hours after the first plasmapheresis session is completed and there must be at least 96 hours between the second and third dose of bortezomib.; Plasmapheresis for 3 consecutive days (treatment days 0, 1 and 2) followed by concomitant bortezomib dosed at 1.3 mg/m^2 as a 3 to 5 second bolus administered by intravenous injection on treatment days 0, 3, 7 and 10. The first dose of bortezomib is administered between 4-8 hours after the first plasmapheresis session is completed and there must be at least 96 hours between the second and third dose of bortezomib.
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: desensitization therapy; bortezomib (VELCADE®); plasmapheresis

Summary:

      The primary objective is to evaluate the efficacy of desensitization therapy, which includes
      VELCADE® (bortezomib) and plasmapheresis, on select sensitized patients awaiting heart
      transplantation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must be able to understand and provide informed consent;

          -  Candidate (as recipient) for a primary heart transplant (single organ transplant);

          -  Calculated panel reactive antibody (cPRA) of greater than 30% with a threshold using
             mean fluorescent intensity (MFI) of 3,000 or standard fluorescence intensity (SFI) of
             60,000;

          -  Status 1 (1A or 1B) enrollment and randomization to occur within 2 weeks after status
             1 listing;

          -  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;

          -  Negative test for HIV (human immunodeficiency virus), HBsAg (hepatitis B surface
             antigen), HBcAb (hepatitis B core antibody), and HCV (hepatitis C virus) antibodies
             within 6 months prior to study entry.

        Exclusion Criteria:

          -  Recipient of multiple solid organ or tissue transplants;

          -  Prior history of organ transplantation;

          -  Women of childbearing potential with a positive serum β-human chorionic gonadotropin
             (β-hCG) pregnancy test.Pregnancy testing is not required for postmenopausal or
             surgically sterilized women;

          -  Currently breast-feeding a child or plans to become pregnant during the timeframe of
             the study follow-up period;

          -  Subject has a hypersensitivity to VELCADE® (bortezomib), boron, or mannitol;

          -  Active systemic infection at time of enrollment;

          -  Any history of serologic positivity to HIV, HBsAg, HBcAb and HCV Ab;

          -  History of malignancy except when noted by an oncology specialist that tumor
             recurrence is low based on tumor type, response to therapy and negative metastatic
             work-up;

          -  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;

          -  Subjects with a platelet count of less than 75,000 within 7 days prior to enrollment;

          -  Subjects with an absolute neutrophil count (ANC) of less than 1,500 within 7 days
             prior to enrollment;

          -  Subjects with >1.5 x ULN (upper limit of normal) total bilirubin;

          -  Subjects with any grade or history of neuropathy;

          -  Any condition that, in the opinion of the investigator, would interfere with the
             subject's ability to comply with study requirements;

          -  Participation in another interventional clinical trial or requiring treatment using
             un-marketed investigational drug(s) within 14 days of start of this trial and
             throughout the duration of this trial.