Clinical trial NCT00820469: Study of the Influence of Plasma Exchange on the Pharmacokinetics of Rituximab
Official title: Influence of Plasma Exchange Therapy on the Pharmacokinetics of Rituximab in Patients Treated for Autoimmune Disorders.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Renal Transplant
Autoimmune Diseases
Keywords: Rituximab
Plasma exchange
Autoimmune diseases
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2009-01-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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.

Eligibility 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

Primary outcomes:
measure: Comparison of the total AUC levels between 2 arms : patients treated by rituximab alone or patients treated by rituximab and plasma exchange
timeFrame: Determination on the overall plasma concentration profile between the start of infusion and three months after the start of infusion
Secondary outcomes:
measure: Determination of amount rituximab eliminated during a plasma exchange
timeFrame: At each plasma exchange
measure: Evaluation of the efficacy of the treatment by CD19+B Cell count
timeFrame: 15 dyas, 1, 2, 3, 6 and 9 months after rituximab infusion
Other outcomes:
Locations:
city: Toulouse
country: France
facility: University Hospital Toulouse
Study officials:
affiliation: University Hospital, Toulouse
name: Jacques Pourrat, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Puisset F, White-Koning M, Kamar N, Huart A, Haberer F, Blasco H, Le Guellec C, Lafont T, Grand A, Rostaing L, Chatelut E, Pourrat J. Population pharmacokinetics of rituximab with or without plasmapheresis in kidney patients with antibody-mediated disease. Br J Clin Pharmacol. 2013 Nov;76(5):734-40. doi: 10.1111/bcp.12098.