Novel collaboration between academia and industry

Authors: F. Pane ¹, F. Cervantes ^2
1 CEINGE Biotecnologie avanzate s.c.a.r.l., Italy; ² Hospital Clinic Provincial de Barcelona, Spain for the Information Letter No.5, August 2008

Introduction

The EUropean Treatment and Outcome Study (EUTOS) for chronic myeloid leukemia (CML) represents an unique collaboration between the European LeukemiaNet (ELN) and Novartis. The EUTOS for CML project:

• was launched in June 2007
• is underpinned by a contract between the University of Heidelberg (legal representative of the ELN-CML group) and Novartis
• is a collaboration that will run for three years, with an option to extend the contract beyond 2010
• is an excellent example of a novel public–private partnership for translational research.

The objectives of the collaboration are to enhance understanding of the nature and management of CML, to improve standardized evaluation and monitoring, and to optimize diagnosis and treatment of CML across Europe. EUTOS for CML comprises four subprojects:
1. an expanded CML Registry with quality controlled outcome, 2. standardized Molecular Monitoring, 3. Pharmacological Monitoring and 4. Spread of Excellence. Each subproject is overseen by a Working Group consisting of EL N members and Novartis representatives. An Executive Board periodically verifies direction and meets results, the next time in a year from now. Significant progress has been made since inception (see Tab.1 for key achievements so far), and physicians and patients from across Europe have engaged positively with the project.

Tab. 1. Key achievements of the EUTOS for CML project (up to July 2008)

Registry
A research plan and core data set have been agreed for in-study and out-study patients About 3,000 in-study patients are already registered Discussion of the prospective patient group has been initiated Scientific committees have been formed Registry Working Group meetings have been held in Munich (April 2008), Copenhagen (June 2008) and Heidelberg (July 2008)
Molecular monitoring
Harmonization of methods and implementation of the international scale is on schedule Standardized results are available in about 40 laboratories in 10 countries
Pharmacological monitoring
The central facility in Bordeaux is ready to accept samples Local facilities across Europe are undergoing standardization
Spread of excellence
Supportive materials and information packs for the other subprojects have been created and distributed An ELN recommendations pocket card and an ELN/EUTOS exhibition booth have been completed The EUTOS for CML website has gone live EUTOS for CML sessions are planned at upcoming ELN CML events

CML Registry

The purpose of this subproject is to expand the already existing EL N-CML registry to cover a significant proportion of CML patients in European countries. The additional funding through EUTOS for CML is enabling the EL N to extend the registry to patients not enrolled in clinical trials, and to centers and countries that have not previously participated participated in the EL N. It is expected that by 2010 around 5,000 patients will be included in total, comprising patients already enrolled in clinical trials (‘in study’ group), patients already registered in existing databases of national/regional study groups or reference centers (‘out study’ group), and newly diagnosed patients on a population basis (‘prospective’ group).
A core data set has been established for the collection of retrospective data from patients in existing studies or national/ regional databases across Europe, and discussions are now underway on the inclusion of prospective data from patients newly diagnosed with CML in 2008 and 2009. Scientific committees have been set up to define key questions that may be addressed with registry data.

Molecular Monitoring

The Molecular Monitoring subproject will facilitate the spread of internationally standardized PCR analysis for the quantification of BCR-ABL mRNA levels and the detection of BCR-ABL mutations. The goal is to standardize the methodology and results of residualdisease monitoring in 50 centers, with at least one per participating country/ region, which will then serve as a national reference laboratory to further standardize
other laboratories in that country. Dilutions of cell lysates have already been sent out to around half of these centers. Results from the analysis of these samples can then be used to calculate laboratory-specific conversion factors, which allow for the representation of all results on a common international scale.

Pharmacological Monitoring

Recent publications (Picard et al. Blood 2007;109:3496-9; Larson et al. Blood 2008;111:4022-8) provide evidence that low trough plasma evels of imatinib may result in inferior treatment outcomes in CML, suggesting that adequate blood levels of imatinib are important for good clinical response. However, until now, the availability of plasma level testing for clinical centers has been limited. The aims of the EUTOS for CML Pharmacological Monitoring subproject are to expand the availability of imatinib monitoring to a European level, and to construct a dosing database to define therapeutic threshold and toxic dose.
Under the terms of the EUTOS for CML contract, a central facility at the Bordeaux University Hospital in France is now available to analyze samples from all over Europe free of charge. In addition, the Bordeaux laboratory is assisting in the establishment of monitoring facilities in European countries, using a standardized, quality-controlled monitoring protocol. The project covers 3000 free tests over two years. In addition, a laboratory kit has been developed to facilitate sample submission by physicians, and to ensure that samples arrive intact and on time.

Spread of Excellence

The Spread of Excellence subproject was created to raise awareness of EUTOS for CML, and to foster EL N activities. It supports all activities that promote realization of the Registry, Molecular Monitoring, and Pharmacological Monitoring subprojects.
A successful EUTOS for CML launch event was held in Budapest in October 2007, with more than 200 press representatives attending or viewing the webcast. In addition, a EUTOS for CML website has been constructed (www.eutos.org), and supportive materials have been eveloped to explain and promote the other three subprojects. EUTOS for CML is also featured in the EL N exhibition booth for major national and international congresses (Fig. 1), and there will be dedicated EUTOS for CML sessions at upcoming ELN CML events.