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

• Status: Terminated
• Trial end date: 2014-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Clinical Trials in Organ Transplantation
• Treatments: Bortezomib

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.