Determination of the pharmacokinetics of rituximab and antibodies to rituximab in patients with a B-cell CD20+ malignancy who are treated with rituximab as single agent or rituximab in combination with chemotherapy or are on maintenance therapy with rituximab

The information about the pharmacokinetics of rituximab and development of
antibodies against rituximab is almost entirely restricted to patients with
CD20+ B-cell malignancies who have been treated with rituximab as single agent,
who were rituximab naïve and received only four courses of rituximab. The
results of these studies showed that the half life of rituximab was dependent
on the tumor load and renal function. There was a considerable inter-patient
variation and the half life became longer after several cycles of treatment
with diminishing tumor load. In these patients, development of antibodies
against rituximab seldom occurred. This is in contrast with patients with
auto-immune diseases who are treated with rituximab, like patients with
Sjögren*s disease: the half life of the rituximab in these patients is
comparable with the half life of normal antibodies and many of these patients
develop antibodies against rituximab.
We wish to get more insight into the pharmacokinetics of rituximab and
development of antibodies against rituximab when it is combined with
chemotherapy or is given as maintenance treatment in patients with CD20+ B-cell
malignancies.
The results of this study will be used for possible improvement of the
rituximab containing therapies in patients with CD20+ B-cell malignancies and
further development of other treatment modalities like radio-immunotherapy with
131I labeled rituximab.

· To get more insight into the pharmacokinetics of rituximab in patients with
CD20+ B cell malignancies who are treated with rituximab containing
chemotherapy or maintenance therapy with rituximab
· To use the results of the data to further improve rituximab containing
therapies for patients with CD20+ B-cell malignancies (including
radio-immunotherapy with rituximab)
· To gain more knowledge about the development of antibodies against rituximab
in patients who are treated with rituximab in combination with chemotherapy or
are on maintenance therapy

Patients with a CD20+ B-cell malignancy who are treated with rituximab
containing regimens or are on maintenance therapy with rituximab will be
informed by their treating physicians in line with the rules of good clinical
practice about this study. Patients who give their informed consent will be
registered into the study. On the day of the treatment with rituximab, 5 ml
EDTA blood will be taken before the start of the therapy. The extra 5 ml EDTA
blood will be taken for each rituximab containing cycle or for each maintenance
treatment until the patient stops with therapy with rituximab. The blood will
be taken by the nurses of the fourth floor or the out patient nursery
department (dagbehandeling) when they introduce the infusion needle for the
administration of rituximab. The blood has to be taken before the rituximab is
given to the patient.
Mrs Tran or one of her colleagues collect the blood samples, the blood will be
centrifuged and stored at the department of pharmacy at -20 o Celsius.
The samples will be brought to the department of Auto-immune Diseases of
Sanquin for the determination of the rituximab levels and antibodies against
rituximab.

none, 5 ml extra EDTA blood taken before each course of rituximab containing
therapy