Safety and Efficacy of Desensitization Therapy in Sensitized Participants Awaiting Heart Transplantation

Inclusion Criteria:

• Subject must be able to understand and provide informed consent;
• Candidate for a primary heart transplant recipient (single organ transplant);
• cPRA of 40% to 70% with a threshold using MFI of 3,000 or SFI of 60,000
• Status 1 (1A or 1B) at the time of listing (listing to occur within 2 weeks prior to enrollment);
• 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, HBsAg, HBcAb, and HCV Ab 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;
• Patient 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;
• Patients with a platelet count of less than 75,000 within 7 days prior to enrollment;
• Patients with an absolute neutrophil count of less than 1,500 within 7 days prior to enrollment;
• Patients with >1.5 x ULN Total Bilirubin;
• Patients 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 an un-marketed investigational drugs within 14 days of start of this trial and throughout the duration of this trial.