The Effect of Rituximab on the Development of Anti-Donor Antibodies
The aim of the study is to find out if Rituximab, which is an antibody against specific white cells involved in rejection, when combined with standard anti-rejection treatment can more effectively reverse the rejection process.
Our hypothesis is that with acute rejection there is activation of B cells and the subsequent development of anti-donor antibodies that ultimately lead to graft loss. More effective therapy targeted at B cells may abort the development of anti-HLA antibodies, prevent renal injury and have a favorable effect on long-term graft outcome.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Effect of Rituximab on the Development of Anti-Donor Antibodies and Resolution of B Cell Infiltration in the Renal Allograft of Patients Undergoing Rejection|
- Change in Biopsy Cell Densities From Baseline to Follow-up [ Time Frame: 1 year ] [ Designated as safety issue: No ]Follow-up biopsy was done 3-6 months after study treatment. Study follow-up monthly for 1 year.
|Study Start Date:||August 2004|
|Study Completion Date:||December 2010|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Rituximab Group: The Rituximab dose is 1000mg (1gm) given as an IV infusion every two weeks for 2 doses (days 1 and 15) and followed up monthly for 1 year. Biopsy was done Baseline and Month 3 and other labs (CBC/Diff, Platelets, HACA, PK, Serum Creatinine, 24-hour protein, HLA antibodies, flow cytometry, and serology testing). Physical exam and vital signs were done.
Rituximab infusion on Day 1 and Day 15
Other Name: Rituxan
Active Comparator: 2
No Rituximab: received standard immunosuppression and was followed up monthly for 1 year. Labs (CBC/Diff, Platelets, HACA, PK, Serum Creatinine, 24-hour protein, HLA antibodies, flow cytometry, and serology testing) vital signs, and physical exam was done.
Drug: No Rituximab
This is a two center, randomized pilot study of the effects of Rituximab on treatment of acute rejection. A total of 24 patients (including patients transplanted at University of California San Francisco and University of Alabama Birmingham) will be enrolled in the study, 16 randomized to Rituximab and 8 to no-Rituximab (control arm). Fifteen (15) subjects will be recruited at UCSF with 10 patients randomized to Rituximab and 5 to no-Rituximab (control arm). If either center is a slow enroller the patient mix could be altered.
This is an open label trial of patients with rejection with B cell infiltrates on kidney biopsy who will be randomized to either receive Rituximab or no Rituximab in and 2:1 ratio. Patients who have rejection on kidney biopsy and on immunohistochemistry there is evidence of B cells infiltration will be enrolled in the study and randomized 2:1 to receive Rituximab or no Rituximab. Rituximab will be administered in 2 doses of 1,000 mg. The first dose will be administered while the patient is still in the hospital being treated for rejection and the second dose will be administered 2 weeks later in the outpatient facility in the GCRC at UCSF. The patients' acute rejection episode will be treated according to standard therapy as per the treating transplant physician. Below is the table (table 1) detailing when the patient will have blood drawn for flow cytometry, anti-HLA antibodies, PK studies, serum creatinine as well as 24 hour urine protein. At 3 months after enrollment in the study, the patient will undergo a follow-up biopsy to determine the extent of the resolution of the cellular infiltrate.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00695097
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35294|
|United States, California|
|UCSF-Kidney Transplant Clinic|
|San Francisco, California, United States, 94143|
|Principal Investigator:||Flavio Vincenti, M.D.||University of California, San Francisco|