Multi-Drug Desensitization Protocol for Heart Transplant Candidates

Study Summary

Background: Patients may develop antibodies (human leukocyte antigen \[HLA\] alloantibodies) to other human tissues via pregnancy, transfusions or previous transplantation, which limits the ability to find an acceptable donor heart for transplantation. Such patients are at high risk for antibody mediated rejection, graft failure, and acute rejection (i.e. death). For successful transplantation, patients must receive organs from donors who lack the HLA antigens that correspond to their alloantibody specificities. No successful desensitization strategy currently exists. Purpose: To determine if desensitization by deletion of immunologic memory with a multi-drug approach including anti-T and B cell therapies and anti-plasma cell therapy can effectively eliminate or significantly reduce alloantibody levels and permit highly sensitized patients to obtain a heart transplant. This therapy is anticipated to remove immunologic memory and will require re-immunization.

Primary Outcome

Percentage of highly sensitized heart transplant candidates, (patients with a CPRA greater than 50%), who have desensitization therapy, and then achieve a reduction in alloantibody such that their CPRA falls below 20%. For an individual patient, the outcome measure time frame is the one year of the Recovery Phase which begins after 218 days from the time that the patient begins the Induction Immunotherapy Phase, which is the same as the end of the Bortezomib Treatment Phase.

Interventions

• DRUG Bortezomib, Thymoglobulin, Rituximab, Gamimune N, (IVIG), Plasmapheresis