Section 4. New Projects Application for Continued Funding. Title Page

Section 4 New Projects Application for Continued Funding Title Page Network title: Competence Network Malignant Lymphoma Name of scientists-in-charg...
Author: Patience Berry
2 downloads 0 Views 26KB Size
Section 4 New Projects Application for Continued Funding Title Page Network title:

Competence Network Malignant Lymphoma

Name of scientists-in-charge:

PD Dr. Martin Bentz PD Dr. Martin Dreyling

Institution:

Abt. Innere Medizin III, Universität Ulm Abt. Innere Medizin III, LMU München

Address:

Robert-Koch-Str. 8, D-89081 Ulm Marchioninistr. 15, D-81377 München

Phone:

+49 (0) 731 / 500-24391 +49 (0) 89 / 7095-3019

Fax:

+49 (0) 731 / 500-24492 +49 (0) 89 / 7095-5550

E-mail:

[email protected] [email protected]

283

Sub-project 13_new: Biologic Risk Factors

Part A – General Statements about the Project A.1 Subject Improvement of the infrastructure for the analysis of biologic risk factors in malignant lymphomas

A.2 Co-investigators Name of scientists: Prof. Dr. L. Trümper PD Dr. J. Wolf 2

1

Institutions: 1 2

Abt. Hämatologie und Onkologie, Universität Göttingen Klinik I für Innere Medizin, Universität zu Köln

Reference Centres for Lymphoma Pathology: Prof. Dr. Alfred Feller, Pathologisches Institut, Medizinische Universität, Ratzeburger Allee 160, 23562 Lübeck Prof. Dr. Martin-Leo Hansmann, Universität Frankfurt, Senckenbergisches Institut für Pathologie, Theodor-Stern-Kai 7, 60596 Frankfurt Prof. Dr. Peter Möller, Universitätsklinikum, Institut für Pathologie und Rechtsmedizin, AlbertEinstein-Allee 11, 89081 Ulm Prof. Dr. Konrad Müller-Hermelink, Universität Würzburg, Institut für Pathologie, Josef-SchneiderStr. 2, 97080 Würzburg Prof. Dr. Reza Parwaresch, Christian-Albrechts-Universität zu Kiel, Institut für Hämatopathologie, Niemannweg 11, 24105 Kiel Prof. Dr. Harald Stein, Universitätsklinikum Benjamin Franklin, Institut für Pathologie, Hindenburgdamm 30, 12200 Berlin

284

Sub-project 13_new: Biologic Risk Factors

Part C – Proposal for a new project C.1 Summary In contrast to acute leukemias, the prognostic impact of biologic parameters in malignant lymphomas is still poorly understood despite significant progress in our knowledge about molecular events leading to the development of this disease. In Germany, there is an excellent organisational structure of large multicentre clinical lymphoma study groups. These internationally renowned trials have led to the improvement of the cure rates of most lymphoma sub-types during the last ten years. The organisational structure of the study groups includes the high quality of the clinical partners, the steering committees and biometrical analyses, and the establishment of reference pathology panels as well as the scientific advisory panels for the various study groups. This set-up provides almost ideal conditions for the analysis of the clinical impact of biologic factors, and is unique and internationally recognised. The key goal of the proposed project is to provide an optimised infrastructure for the collection of fresh tumour tissue and to create a closer interaction between clinicians and reference pathologists on the one hand and scientists involved in the research into biologic risk parameters on the other hand. Thereby, transfer of novel biologic findings into the clinical evaluation in order to determine their clinical relevance will be facilitated. To achieve this goal, established structures of the network will be further optimised and additional resources will be provided. Specific scientific questions will not be addressed by this infrastructural project; these will have to be funded separately through specific grants. The project strongly depends on a close collaboration with sub-project 2 (“Telematics and Quality Management”) as well as sub-project 3 (“Pathology”) and is complimentary to these sub-projects. The optimised infrastructure created by our project will be an important prerequisite for a future national scientific networking project originating from the competence network investigating biologic risk factors in lymphomas. This scientific network will be applied for to the “Deutsche Krebshilfe” under the title “Molecular Mechanisms and Targets in Malignant Lymphoma” and will provide an important funding structure for specific scientific projects.

C.2 State-of-the-Art and Own Previous Work State-of-the-Art Within the last decade, clinical risk factors were identified both for the Non-Hodgkin’s lymphomas as well as for Hodgkin’s disease (Shipp et al., 1994; Hasenclever and Diehl, 1998; Frederico et al., 2000). This allowed a categorisation of lymphoma patients into defined clinical risk groups. These risk groups are defined by common clinical parameters that can be assessed easily in clinical practice. The biological changes underlying these markers, however, are not defined at present. For example, in favorable clinical risk groups, there are significant proportions of patients with poor outcomes; similarly, in high-risk groups based on clinical parameters, there is a proportion of patients with a favorable outcome. For the accurate prediction of the risk profile, additional parameters that reflect the true biology of these lymphomas are required. In leukemias, biologic risk factors (i.e. genomic aberrations) have been established as most important criteria for the stratification of therapies in the context of clinical trials (Hoelzer und Goekbuget, 2000; Döhner et al., 2000). In lymphomas, only few studies regarding the prognostic relevance of such biologic parameters have been performed. The main reason for this is the poor availability of fresh tumour tissue from patients, who have been treated within clinical phase-III trials. To the present day, most published studies on the clinical impact of biologic parameters have been performed on heterogeneous cohorts of patients and are of limited use for the stratification in future trials. The collection of fresh tumour tissues obtained from patients, who have been treated within trials of the study groups of the competence network will allow an analysis of

285

Sub-project 13_new: Biologic Risk Factors

histopathologically and clinically well characterised and homogeneously treated patient cohorts. Own previous work Within the Competence Network Malignant Lymphoma, there are excellent prerequisites for the analyses of biologic risk parameters in lymphomas. The major study groups have established scientific committees for such biologic studies: German Hodgkin’s Study Group (V. Diehl, J. Wolf), German Study Group High-grade Lymphomas (L. Trümper, M. Bentz); German low-grade Lymphoma Study Group (W. Hiddemann, M. Dreyling). In addition, there is a well-established network of internationally renowned lymphoma pathologists supporting the clinical trials. These pathology reference centres are ideal partners for the collection and characterisation of fresh tumour tissues that can be used for studies addressing molecular mechanisms in lymphomas and for analyzing the clinical relevance of novel molecular markers. Within these trial groups, successful analyses of biologic risk factors have been initiated using tumour material as well as sera and peripheral blood lymphocytes of study patients. Some of these projects have already received external funding by the Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe and other grant agencies. Moreover, they resulted in a large number of publications in internationally renowned journals (for selected references, see appendix). In February 2000, members of all clinical study groups and reference pathologists attended a conference at the Reisensburg castle (near Ulm, Germany). At this meeting, the procedure for the collection of fresh tumour tissue was discussed between clinicians, pathologists and basic researchers and an optimised algorithm was agreed upon (see also attached “Reisensburg-Konsens”). However, based on several logistic as well as financial shortcomings, this algorithm could not be broadly implemented until now despite the interest of clinicians and pathologists alike to support this important initiative. During the annual meeting of the German Society for Hematology and Oncology in Graz (October 2000), representatives of all study groups gathered to discuss further steps for the optimisation of the infrastructure for biologic studies within the clinical trial groups. At this meeting, it was decided, that a separate project should be suggested for the Competence Network Malignant Lymphoma that focuses on the infrastructure for such biologic studies. Key References Döhner, H., Stilgenauer, S., Benner, A., Leupold, E., Kröber, A., Bullinger, L., Döhner, K., Bentz, M., Lichter, P.: Genomic aberrations predict survival of patients with B-cell chronic lymphocytic leukemia. New England Journal of Medicine 343:1910-1916, 2000. Federico, M., Vitolo, U., Zinzani, P.L., Chisesi, T., Clò, V., Bellesi, C., Magagnoli, M., Liberati, M., Boccomini, C., Niscola, P., Pavone, V., Cuneo, A., Santini, G., Brugiatelli, M., Baldini, L., Rigacci, L., Resegotti, L.: Prognosis of follicular lymphoma: a predictive model based on a retrospective analysis of 987 cases. Blood 95: 783-789, 2000. Hasenclever, D., Diehl, V.: A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. New England Journal of Medicine 339(21):1506-14, 1998. Hoelzer, D., Gokbuget, N.: New approaches to acute lymphoblastic leukemia in adults: where do we go? Seminars in Oncology 27(5):540-59, 2000.

286

Sub-project 13_new: Biologic Risk Factors

Shipp, M.: Prognostic factors in aggressive Non-Hodgkin´s lymphoma. Blood 93:11651173, 1994.

C.3 Aims 1. Optimisation of the infrastructure for the collection of fresh and/or cryopreserved lymphoma tissues from study patients. 2. Improvement of the interaction between groups involved in scientific projects. Furthermore, an efficient communication should be established between such research groups and the clinicians and pathologists directly caring for the patients.

C.4 Methodological approach The project is aimed at the improvement of the infrastructure for research into biologic risk factors. In particular, the availability of fresh or cryopreserved tumour tissue as well as the interactions between scientists involved in these molecular studies will be improved. For this purpose, a well-organised infrastructure for sample shipping and scientific networking will be established (see C5, Work plan).

C.5 Work plan Improvement of the infrastructure for the analysis of biologic risk factors in malignant lymphomas

2002 4.Q

2003 1.Q

2.Q

3.Q

Schedule

Logistic support

I-IX.2004 4.Q

1.Q

2.Q

3.Q

Planned funding by transregional network focussing on the

Collection of Samples

analysis of molecular risk factors in lymphomas

Workshop

nd

2

Report

Collection of fresh/cryopreserved tumour tissues Logistic support in the clinical centres For an optimised documentation of patient data, a decentral structure of “network assistants” is established within the competence network. As primary contact persons, these network assistants support large non-university centres participating in the clinical studies by answering questions on the study procedures and by monitoring the patients’ documentation. They visit these centres, which contribute a major proportion of patients to the trials, on a regular basis. Therefore, network assistants are ideally suited to support the logistics required for the collection of fresh/cryopreserved tumour tissues and the documentation of the relevant parameters. They should promote knowledge about the importance of such a 287

Sub-project 13_new: Biologic Risk Factors

collection and should communicate, that sending fresh tissue to the reference centres comprises a regular component of the initial workup for each patient considered for inclusion into one of the trials. An alternative approach for participating clinical/pathological centres could be the local collection of cryopreserved tissue samples: for this purpose, cryopreserved tissue can be stored at the local pathology department. The network assistant would coordinate the regular shipping of the samples to the central reference sites (listed under A.2). Network assistants will be trained by the applicants at a special training session in Cologne to provide the necessary knowledge for communicating the importance of the collection of fresh/cryopreserved tumour tissues. In addition, they will get the essential information about the modalities for sample shipping to communicate these to the local clinical centres. The applicants as well as the trial centre offices will be actively involved in the support of these assistants as well as in the monitoring of the sample shipping. Financial support for sample shipping To facilitate an adequate collection of samples, the shipping costs have to be provided by the competence network. In addition, a financial compensation for the additional work involved in identifying suitable patients and coordinating the preparation of shipping is required. This compensation will be paid for all cases that prove to be malignant lymphomas, regardless of their inclusion in one of the studies. The central coordination of such compensation will also allow to obtain reliable information on fresh/cryopreserved samples that have been collected within the competence network. Improvement of communication To establish a close communication between scientists working on the identification of biologic risk factors in lymphomas and to promote the knowledge about the possible clinical benefit of these studies among clinicians and pathologists, a yearly status symposium will be performed. Organisational and financial support of such status symposia by the competence network is an important prerequisite. In the context of this symposium, all groups performing studies on the tumour samples provided by the network will report about the progress of their work. These meetings will also be an essential element of the planned research network on molecular risk factors in malignant lymphomas. The applicants of this project in coordination with the steering board of the competence network and the reference pathology centres will set down guidelines for scientists wishing to perform studies and coordinate the work of the scientific advisory boards of the trial groups. Only scientific groups submitting detailed proposals including ethics committee votes and proof of financing or grant applications will receive access to the material once their applications have been evaluated by the advisory boards. Scientists have to report about the progress of these projects at the annual status symposium.

C.6 Networking The primary goal of this proposal is the improvement of the infrastructure for research projects, which aim at the identification of biologic risk factors in lymphomas. This will provide a major support for scientific projects that have been funded by other institutions. These projects will thus receive a direct benefit from the competence network. To achieve this goal, a close collaboration with sub-projects 1, 2 as well as sub-project 3 (“Pathology”) is required. In addition, our project will provide important prerequisites within the network to allow the application and performance of a large transregional scientific network focussing on the analysis of molecular risk factors in lymphomas. Such a scientific extension of the competence network will be applied for at the “Deutsche Krebshilfe”. The proposed project will strongly support the internal and external coordination of this application and the establishment of the scientific network in direct collaboration with all other projects of the competence network. 288