Study of the Influence of Plasma Exchange on the Pharmacokinetics of Rituximab (PK-rituximab)
Rituximab (a monoclonal antibody raised against CD20) is used to treat various immune disorders. In some cases such as treatment of humoral acute rejection of renal transplant, thrombotic thrombocytopenic purpura, vasculitis or cryoglobulinemia, rituximab is often associated with plasma exchange. The pharmacokinetic of the rituximab can be affected by plasma exchange but the knowledge is poor in this matter.
The aim of the study is to explore the influence of plasma exchange on the pharmacokinetic of rituximab.
The results of this study should conclude if plasma exchange leads to a significant decrease of plasma concentration of rituximab or not, and if the decreased of the concentration is associated with a decrease in efficacy.
|Renal Transplant Autoimmune Diseases||Drug: Rituximab 375 Drug: rituximab 1000||Phase 4|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Other
|Official Title:||Influence of Plasma Exchange Therapy on the Pharmacokinetics of Rituximab in Patients Treated for Autoimmune Disorders.|
- Comparison of the total AUC levels between 2 arms : patients treated by rituximab alone or patients treated by rituximab and plasma exchange [ Time Frame: Determination on the overall plasma concentration profile between the start of infusion and three months after the start of infusion ]
- Determination of amount rituximab eliminated during a plasma exchange [ Time Frame: At each plasma exchange ]
- Evaluation of the efficacy of the treatment by CD19+B Cell count [ Time Frame: 15 dyas, 1, 2, 3, 6 and 9 months after rituximab infusion ]
|Study Start Date:||September 2008|
|Study Completion Date:||January 2010|
|Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
Patients treated by rituximab
Drug: Rituximab 375
rituximab 375 mg/m2 IV weekly, during 4 weeks
Patients treated by rituximab and plasma exchange
Drug: rituximab 1000
rituximab 1000 mg IV, two infusions on day 1 and day 15
Twenty patients will be enrolled: ten patients treated by rituximab and ten patients treated by rituximab and plasma exchange. The plasma concentration of rituximab and the efficacy of the treatment will be compared between the two groups of patients.
The enrollment in the study will not change the treatment of patients except for blood sampling.
Each patient will undergo fifteen blood samples between the start of infusion of rituximab and three months after the start of infusion. For the patients who will undergo plasma exchange, three additional blood samples will be performed at each plasma exchange (at the start, at the end and one day after the plasma exchange) and a sample of the plasma exchanged will be keep.
The plasma concentration of rituximab will be determined by ELISA method (Enzyme Linked ImmunoSorbent Assay) The pharmacokinetic analyse will consist in the determination of the Area Under the Concentration Curve (AUC) by a non compartmental approach.
The AUC levels will be compared (using the t Student test) between the two populations of patients (patients treated by rituximab, versus patients treated by rituximab and plasma exchange) The efficacy of the treatment will be evaluated by the CD19+ B Cell count.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00820469
|University Hospital Toulouse|
|Toulouse, France, 31000|
|Principal Investigator:||Jacques Pourrat, MD||University Hospital, Toulouse|