Clinical Trial: Effects of Rituximab and Mycophenolate Mofetil (MMF) on Highly Sensitized Patients Awaiting Renal Transplant

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Highly Sensitized Patients: Effects of Rituximab and Mycophenolate Mofetil (MMF) On Anti-Human Leukocyte Antigen (HLA) Antibody Levels In Patients Awaiting Cadaveric Renal Transplant.

Brief Summary: This is a 12-month phase 2, prospective, open label study to evaluate the effect of rituximab with mycophenolate mofetil (MMF)on the PRA of 14 highly sensitized patients who just completed an 8 month trial of MMF treatment alone. PRA values obtained at study enrollment and at 6 and 12 months on combined therapy as well as the rates of transplant will be compared and evaluated using descriptive analysis.

Detailed Summary:

BACKGROUND: Patients who have been exposed to human tissue by prior transplants, blood transfusion or pregnancy may develop and maintain anti-bodies against these foreign human cells (SENSITIZATION). As a result of sensitization these patients are more likely to reject an organ donated from an individual who possesses a similar human cell marker (ANTIGENIC)profile. These sensitized patients will remain on the kidney transplant waiting list up to twice as long as those who are not pre-sensitized.

The Panel of Reactive Antibodies (PRA) is a test panel used to measure the patient reactivity to human leukocyte cell antigens (HLA). A PRA of 75% means the patient reacted to 75% of the antigens on the panel. A high PRA indicates that the subject already has antibodies and is highly SENSITIZED. Spontaneous decreases in PRA titers rarely occur. Thus the probability of transplantation in sensitized patients is significantly decreased.

RATIONALE for use of Rituximab:

By reducing specific B-cell populations Rituximab is currently used as a treatment in auto-immune diseases such as lupus erythematosus and rheumatoid arthritis and some cancers such as B-cell non-Hodgkin's lymphoma. It has been reported to have a potential roll in decreasing anti-human lymphocyte (HLA) antibodies post transplant. More studies are needed to assess its possible benefit among pre-transplant patients. Vierira et al. ["Rituxan for reduction of anti-HLA antibodies in patients awaiting renal transplantation", Am J Transplantation 2002;2:A870] reported on the use of rituximab in sensitized patients. Nine patients on dialysis with a PRA > 50% were treated with rituximab (n=3 per group) at 50, 150, or 375mg/m2. No significant change was seen in WBC, hemoglobin, platelet count, chemistry, liver enzymes
Sponsor: University of Washington

Current Primary Outcome: The Number of Subjects Who Experience a Decrease in Their Panel of Reactive Antibodies (PRA) at 6 Months Post Rituximab Infusion. [ Time Frame: Month 6 from start of study ]

the number of subjects who experience a decrease in their Panel of Reactive Antibodies (PRA) at 6 months and 12 months post Rituximab infusion


Original Primary Outcome: Primary Efficacy Endpoint: Proportion of subjects who achieve a PRA value below 10% within 6 months of study initiation.

Current Secondary Outcome:

  • The Number of Subjects Who Experience a Change From Baseline in Their Panel of Reactive Antibody (PRA) Titers at 12 Months Post Rituximab Infusion. [ Time Frame: Month 12 from start of study ]
  • The Number of Subjects With a Negative Crossmatch at the Time of Transplant. [ Time Frame: Month 12 from start of study ]


Original Secondary Outcome:

  • Secondary Efficacy Endpoints: Change from baseline in subject's PRA at 4, 6, and 8 months
  • Proportion of subjects with a negative crossmatch


Information By: University of Washington

Dates:
Date Received: March 9, 2007
Date Started: December 2006
Date Completion:
Last Updated: March 30, 2010
Last Verified: March 2010