Lymphoma SPORE Core Resources

The University of Iowa/Mayo Clinic Cancer Center (UI/MC) SPORE in Lymphoma comprises four joint UI/MC research projects, and three scientific core resources constructed around a theme of non-Hodgkin lymphoma and consolidated by an Administrative Core. The SPORE also contains Career Development and Developmental Research Programs, and fosters a number of collaborations, including with the Molecular Epidemiology Resource, developed during the first Lymphoma SPORE award cycle.

Core 1 - Administrative Core (Director George Weiner, M.D., University of Iowa; Co-Director Thomas Witzig, M.D., Mayo Clinic)
Core 2 - Biospecimens Core (Director Ahmet Dogan, M.D., Ph.D., Mayo Clinic; Co-Director Sergei Syrbu, M.D., University of Iowa)
Core 3 - Biostatistics and Bioinformatics Core (Director Susan Geyer, Ph.D., Mayo Clinic; Co-Directors Terry Braun, Ph.D., and Brian Smith Ph.D., both of the University of Iowa)
Core 4 - Clinical Research (Director Brian Link, M.D., University of Iowa; Co-Director Thomas Habermann, M.D., Mayo Clinic)

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Core 1
Administrative Core (Director George Weiner, M.D., University of Iowa; Co-Director Thomas Witzig, M.D., Mayo Clinic)

The overall goal of the Administration Core is to stimulate research in lymphoma and to expedite the translation of discoveries into new and better methods of prevention, detection, and treatment of lymphoma. The Administration Core served well as the organizational hub of the UI/MC SPORE during the initial funding period, and it continues to provide an organizational structure designed to efficiently coordinate the activities of the research projects, scientific cores, and developmental programs (Developmental Research Program, Career Development Program) of the UI/MC SPORE. It also enhances communication between investigators at the two institutions.

The Core is responsible for coordinating the function of the SPORE committees including the Executive Committee and the External Advisory Committee. Drs. Weiner and Witzig function well as a team and work collaboratively to provide expertise in laboratory and clinical lymphoma research. They have extensive administrative experience and are well qualified to provide leadership and direction for the UI/MC SPORE.

The Administration Core supports SPORE activities by:

• Providing leadership, organizational support, and financial management for UI/MC SPORE investigators
• Coordinating monthly videoconferences and quarterly meetings of UI/MC SPORE investigators, as well as the ongoing scientific review of SPORE research projects and cores, and the visits of the external advisors
• Providing the infrastructure for the selection and support of the best and most promising projects as outlined in SPORE guidelines
• Facilitating information transfer to the scientific community via professional and public means
• Providing structure for the establishment and nurture of collaborations to facilitate and expand lymphoma research
• Assuring input from patient advocates
• Fostering trainee development

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Core 2
Biospecimens Core (Director Ahmet Dogan, M.D., Ph.D., Mayo Clinic; Co-Director Sergei Syrbu, M.D., University of Iowa)

The Biospecimens Core provides a coordinated, centralized, and dedicated Core for the procurement, processing and annotation of biospecimens from lymphoma patients and patients with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). The goal of the Biospecimens Core is to procure a variety of biologic specimens on all patients involved in UI/MC SPORE protocols and all newly diagnosed lymphoma patients seen at the University of Iowa and the Rochester, Minn., campus of Mayo Clinic.

The specific aims of the Biospecimens Core are to:

• Collect, process, distribute, and bank cells from fresh tumor, frozen tumor tissue, paraffin-embedded tumor tissue, serum/plasma, and genomic DNA from lymphoma and SLL/CLL patients
• Track all biospecimens in the Biospecimens Tracking Database
• Serve as a resource of expertise, collaborative support (including other National Institutes of Health grants), and service for projects involving:
• • Pathology review/classification
  • Immunohistochemistry
  • In situ hybridization
  • Fluorescent in situ hybridization
  • Laser capture microdissection
  • Tissue arrays
  • Digital image analysis

All specimens are collected and processed under tight quality control, and distributed to UI/MC SPORE researchers or banked for future SPORE research projects. These activities are tracked using a sophisticated database that merges the activities at Iowa and Mayo, and allow integration with clinical and other data collected in research projects. During the last grant cycle, the Core consented over 1,300 newly diagnosed lymphoma patients and over 350 previously diagnosed lymphoma patients for use of pathology tissues. In most of these patients the SPORE has banked serum and DNA, and on over 500 patients the Biospecimens Core has processed and banked cells from fresh tissue available after clinical work-up.

The Core supports multiple full and developmental projects, including those of Career Development awardees. The Core has also partnered with other projects that have obtained extramural funding to support epidemiologic and family studies, and has provided key infrastructure for the Molecular Epidemiology Resource. In the current grant cycle, the Core will continue to accrue new patient samples to the bank and work with investigators to utilize this increasingly valuable resource to support translational research projects in lymphoma.

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Core 3
Biostatistics and Bioinformatics Core (Director Susan Geyer, Ph.D., Mayo Clinic; Co-Directors Terry Braun, Ph.D., and Brian Smith Ph.D., both of the University of Iowa)

The Biostatistics and Bioinformatics Core provides statistical collaboration and data management support for each of the SPORE projects, the developmental projects, and the other Cores. In addition, the Core also provides collaboration and support in bioinformatics and computational biology research for SPORE projects as appropriate. The Core was responsible for establishing the infrastructure to link the Lymphoma clinical and research databases between the University of Iowa and Mayo Clinic, and continues to maintain it. This system allows web-based registration and data entry from both sites into a common database.

Core support includes developing statistical plan for clinical trials, including:

• A Phase I Trial of CpG 7909, Rituximab Immunotherapy, and Y-90 Zevalin Radioimmunotherapy for Patients With Previously Treated CD20+ Non-Hodgkin Lymphoma
• Phase II Evaluation Of FTI (RII5777) In Treatment Of Relapsed And Refractory Lymphoma
• A Phase I Study of Alefacept (AmeviveTM) in the Treatment of Cutaneous T-Cell Lymphoma and Peripheral T-Cell NHL

This Core provides data management for each trial, monitors adverse events in collaboration with the Clinical Research Core, and prepares data summaries for manuscript preparation. Each of the projects presented in this application reflects input from members of the Core on study design, analysis plan, and bioinformatics needs. These projects span a wide range of approaches and required analyses. The Core builds upon the innovative and time-tested procedures and systems developed by Mayo Clinic, which houses one of the largest statistical groups in the country — members have collaborated on more than 8,000 clinical and basic science research studies since 1966; as well as the Coordinated Laboratory for Computational Genomics at the University of Iowa founded in 1996.

The Core provides statistical and bioinformatics support across different fields, including:

• Epidemiological studies
• Basic sciences including translational and immunologic correlative studies
• Gene microarray and imaging
• Clinical trials
• Gene and mutation discovery
• Expression analysis and genomics
• Information management

The comprehensive nature of the Core, which has activities at both Mayo Clinic and the University of Iowa, assures each SPORE investigator access to statistical and bioinformatics expertise that includes:

• Collaborative development of study designs and analysis plans
• State of the art data analysis and interpretation
• Data management resources
• Abstract and manuscript preparation

This core also provides a mechanism for the management and integration of both existing and newly-collected data through consistent and compatible data handling. Areas of support include database development, data form development and processing, data collection and entry, data archiving, quality control, and management of information relating to gene mutation identification and genotyping data for disease linkage experiments. This Core complements and assists the efforts of the Clinical Research and Biospecimens Cores by providing superior data management and experience with tissue registries.

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Core 4
Clinical Research (Director Brian Link, M.D., University of Iowa; Co-Director Thomas Habermann, M.D., Mayo Clinic)

The UI/MC SPORE Clinical Research Core (CRC) has as its primary goal to be the direct translational link between research projects and clinical research emanating from these projects. The CRC coordinates the development of clinical trials, assists in patient accrual, manages and reports adverse events to appropriate agencies, and provides quality control on clinical trial data. The CRC also hosts the Molecular Epidemiology Resource. The CRC provides a critical link between clinical research and the specific projects and cores. The CRC is co-directed by Brian Link, M.D., at the HCCC and Thomas M. Habermann, M.D., at the MCCC. Other key members of the CRC are Protocol Development Coordinators (PDC), Clinical Research Associates (CRA), and Research Assistants (RA) located at both sites. The PDC functions with the PI and IRB to develop and activate the clinical trial and consent form. The CRA and RA assists in recruiting patients to the trials, schedules protocol tests, and collaborates with the Biospecimens Core and the specific research projects to ensure that translational research samples from patients are obtained according to protocol guidelines. The CRA and RA arranges for data entry into the Biostatistics and Bioinformatics Core. During the previous funding period, the CRC was very active and developed 4 clinical trials that accrued 113 patients. In addition, the Molecular Epidemiology Resource accrued 1,331 eligible patients through December 31, 2005. The CRC has worked with the PIs to develop the 4 projects in this competitive renewal and is in the process of protocol development for clinical trials outlined in Projects 1, 2, and 4. In addition, the CRC will provide ongoing support for the Molecular Epidemiology Resource that is being used in Project 3 and a developmental project, and is expected to be an increasingly valuable resource as it matures. The CRC will continue to recruit patients to the 4 trials that remain active from the first funding period and follow patients already enrolled until protocol endpoints are met. The CRC is also responsible for the clinical trials monitoring plans, which have been fully developed at both sites. These monitoring plans assure that the appropriate expertise is available to review the patient protocols, obtain IRB approval, and provide periodic review of ongoing protocol review to maximize patient safety. In summary, the CRC has been an extremely valuable resource during the first funding period. It has functioned at a high level and will be a very important core in the next funding period to support the clinical trials research, translational research projects, and epidemiology projects.

The UI/MC SPORE invested heavily over the past grant cycle in the development of the core resources, most notably an integrated clinical, epidemiologic and biospecimens database known as the Molecular Epidemiology Resource, which was developed as part of previously-funded Project #5, and is now a stand-alone research endeavor. Patient follow-up and expanded information gathering is conducted under the auspices of the Molecular Epidemiology Resource. Medical records are collected and abstracted when there are any recurrences/progressions or second cancer (including myelodysplastic syndromes). For decedents, medical records and death certificates are collected and abstracted.