EUTOS Pharmacological Monitoring Structure  · 

Project structure

Lead investigators are:

• F.X. Mahon, University of Bordeaux, France
• F. Guilhot, Poitiers, France
• Novartis representative: P. Schuld

Prescribing physicians will be informed of the availability of the dosing service at conferences or directly by European LeukemiaNet and Novartis. Dosing will be performed for the first three years at the Bordeaux university hospital under the responsibility of Prof. Mathieu Molimard and following the protocol currently used for France for sample taking, shipment and dosing. Briefly, patients will be informed by an explanatory leaflet (appendix a) and have a blood sample taken 24h±3h following the last imatinib dose and during the normal therapeutic follow-up. A leaflet detailing this procedure will be made available to the physicians (appendix b). The prescribing physician will be asked to fill in a questionnaire (appendix c) regarding: the reason for the pharmacological monitoring; date and time of sampling as well as the last imatinib dose; date of treatment initiation, co-medication; the evolution of the pathology, Ph1 status and BCR-ABL mRNA transcript. The blood sample and the questionnaire will be sent to the dosing laboratory using an approved carrier (e.g. DHL) at an ambient temperature (< 30°C) within one week. Dosing will be carried out at the Bordeaux centre following the guidelines for good practice and following the protocol described by Titier et al., Ther Drug Monit (2005). The latter uses a liquid/liquid extraction and HPLC coupled with mass spectrometry in tandem. Samples are stored at –20°C at the dosing laboratory and conserved for further analysis at the request of the prescribing physician or in the event of toxicity in order to determine the biochemical or pharmacological mechanism involved. All samples, questionnaires and data will be securely stored.

At the same time, one or two laboratories of the participating countries will be selected by the European LeukemiaNet (represented by F. Guilhot) in coordination with Novartis to become imatinib dosing centers and to disseminate the dosing technique to other institutions of their respective countries. Selected laboratories will adopt the same protocol as described by Titier et al. 2005 for trough imatinib plasma concentration determination by collaboration with the Bordeaux centre which will provide the protocol and Novartis which will provide the imatinib associated materials required (i.e. imatinib powder, its metabolite and the internal standard). Each laboratory will be free to adapt the protocol to the equipment at their disposal. A crosscheck will be organised by the Bordeaux centre before the dosing laboratory receives certification. Briefly the Bordeaux centre will prepare and send a linear range of eight spiked blank plasma samples (corresponding to part of the calibration range used) and 12 non-linear plasma samples (from either pooled or single patient plasma, spiked plasma or internal controls used at the Bordeaux centre). A regular quality-control system will subsequently put in place, managed and centralised by the Bordeaux centre. Every two months, three samples will be sent to the dosing laboratories (either pooled or single patient plasma or spiked plasma). The volume of material sent to each laboratory will correspond to twice the volume required for dosage in case of technical incidents.

Possible participating laboratories:

Data collected during the three years will be centralised in a secure database and analysed by the department of Pharmacology of the Bordeaux University Hospital in collaboration with F.X. Mahon to investigate the therapeutic threshold and the toxic concentration.

Created by: Hellenbrecht , generated 2007/12/19 , last changed: 2010/04/07