PK-rituximab: Study of the Influence of Plasma Exchange on the Pharmacokinetics of Rituximab
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Patients treated by rituximab |
Drug: Rituximab 375
rituximab 375 mg/m2 IV weekly, during 4 weeks
|
| Experimental: 2 Patients treated by rituximab and plasma exchange |
Drug: rituximab 1000
rituximab 1000 mg IV, two infusions on day 1 and day 15
|
Outcome Measures
Primary Outcome Measures
- Comparison of the total AUC levels between 2 arms : patients treated by rituximab alone or patients treated by rituximab and plasma exchange [Determination on the overall plasma concentration profile between the start of infusion and three months after the start of infusion]
Secondary Outcome Measures
- Determination of amount rituximab eliminated during a plasma exchange [At each plasma exchange]
- Evaluation of the efficacy of the treatment by CD19+B Cell count [15 dyas, 1, 2, 3, 6 and 9 months after rituximab infusion]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patient who should be treated by rituximab for various autoimmune diseases or humoral acute rejection of renal transplant
-
Patient older than 18 years old
-
Patient who have signed the written informed consent form
Exclusion Criteria:
-
Patient presenting a contra indication to rituximab (hypersensitivity, active infection, severe cardiac failure (NYHA class IV))
-
Blood sampling impossibility
-
Pregnant or breasting women
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Toulouse | Toulouse | France | 31000 |
Sponsors and Collaborators
- University Hospital, Toulouse
Investigators
- Principal Investigator: Jacques Pourrat, MD, University Hospital, Toulouse
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 07 140 03