Rituximab Treatment to Block HLA Antibodies in Renal Transplant Recipients
The purpose of this study is to determine if administration of rituximab blocks the development of donor specific antibodies (DSA) in transplant recipients who have developed renal dysfunction and DSA after renal transplant. It is hoped that by blocking DSA production renal function will stabilize or improve.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of Rituximab Treatment to Inhibit HLA Antibodies in Renal Allograft Recipients|
- Negative DSA by Luminex beads or ELISA [ Time Frame: at 12 months post study medication ] [ Designated as safety issue: No ]
- Lack of C4d deposition in peritubular capillary [ Time Frame: on 12 month renal biopsy ] [ Designated as safety issue: No ]
- Renal allograft function: Serum creatinine, Calculated creatinine clearance, Urine protein, Urine protein-creatinine ratio [ Time Frame: 12 months after study entry compared to the baseline ] [ Designated as safety issue: Yes ]
- Change in chronic rejection pathology indices [ Time Frame: on 12-month renal biopsy compared to baseline biopsy. ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2005|
|Study Completion Date:||November 2007|
|Primary Completion Date:||November 2007 (Final data collection date for primary outcome measure)|
this study has only one arm as the treatment group
All subjects will be treated with Rituximab 1000 mg (1 g) intravenously on days 1 and 15.
Other Name: Rituxan
A long established risk factor for late renal allograft loss is the development of DSA. Recent studies from our group and others have shown that these antibodies are probably responsible for chronic rejection by attacking the vascular endothelium and fixing complement (detected as C4d in renal biopsies). Studies in humans and monkeys have shown that circulating antibody and complement deposition precede the development of chronic graft injury. Interruption of antibody production is a potential beneficial strategy to prevent late graft loss from this mechanism.
Therapeutic regimens that have been used in an attempt to deplete HLA or ABO antibodies include plasmapheresis, IVIg, tacrolimus and mycophenolate mofetil (MMF), and anti-CD20 (rituximab). Of these regimens, the most specific is anti-CD20, rituximab (rituxan), a therapy now FDA approved for B cell proliferative diseases. Although initially introduced for the treatment of neoplasm, the humoral immunosuppressant effects of rituximab have been shown to have clinical significance. Rituximab interferes with both primary and secondary humoral responses by eliminating B-cells prior to antigen exposure, thus interfering with differentiation into antibody secreting cells and specific antibody production.