Transplant Alphabet Soup CIBMTR, NMDP, SCTOD, BMT CTN, RCI BMT,.

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1 Transplant Alphabet Soup,, SCTOD, BMT CTN, RCI BMT, Impaired Health Basic Biomedical Human Studies of Safety/ Efficacy Science and Knowledge Practice and Health Decision Making Effectiveness vs Efficacy Quality/ Access Improvement Improved Health From: Sung et al Central challenges facing the national clinical research enterprise JAMA 2003;289: BUS06_1ppt Impaired Health - low access, poor HCT in HCT: Roles of, SCTOD and The Grew Out of Two Important Collaborative Efforts in BMT Basic Biomedical new HCT drugs, strategies Human Studies of Safety/ Efficacy Effectiveness vs Efficacy who should vs does get HCT and why? Science and Knowledge Quality/ Access Improvement Practice and Health Decision Making Optimal HCT Treatment Improved Healthmore successful transplant s International Bone Marrow Transplant Registry (IBMTR) National Marrow Donor Program () DBV06_22ppt IBMTR Voluntary registry established in years after the first successful HCTs At a time when there were ~ 12 transplant centers, < 50 transplants a year worldwide Maintained a database of clinical information on recipients of autologous and allogeneic hematopoietic stem cell transplants in ~450 centers in 47 countries Provided scientific and statistical support for analyzing those data 1986 US government appropriated funds to establish the National Bone Marrow Donor Registry (Donor Panel) 1988 US Organ Transplant Amendments Act mandated collecting outcome data (Recipient Registry); also collects donor ~150 transplant centers and 90 donor centers Repository with matched recipient/donor blood samples DBV06_23ppt DBV06_24ppt 1

2 OrgCht09_1ppt CENTER FOR INTERNATIONAL BLOOD AND MARROW TRANSPLANT RESEARCH Established July 2004 A research collaboration between the International Bone Marrow Transplant Registry and the National Marrow Donor Program to support clinical research in BMT & related fields All of the former IBMTR Operations IBMTR Medical College of Wisconsin Operations Department of IBMTR 1985 (year of first major NIH funding) : 200 centers 1,000 transplants 35 publications Mortimer M Bortin, MD Scientific Director Medical College of Wisconsin Al Rimm, PhD Statistician D Etta Waldoch Sharon Meiers Diane Knutson Data Management Karen Gurgul Asst Location of Centers Participating in the, 2009 Organizational Structure Chief Scientific Director Mary M Horowitz, MD, MS Associate Scientific Director for Data Operations AssociateScientific Director Business Manager Chief for -MSP JD Rizzo, MD, MS SA Lorenz Statistical Director D Confer, MD J Klein, PhD Statistical Faculty Medical Faculty Director, Director, IT Program Vice-President Business Manager Scientific PhD Statisticians Sr Advisor H-J Khoo Data Operations -MSP PA Vespalec Services K-W Ahn, PhD D Weisdorf, MD* R King, MPH R Bajorunaite, PhD M Setterholm Associate Scientific Programmers/ B Logan, PhD Director Analysts Staff T Wang, PhD M Eapen, MD, MS P Fen, MS, MS M-J Zhang, PhD Scientific A Liu, MS Scientific C Fihn Specialist Services SL Finneran Visiting Professor Directors B Liu, MS SK Meiers DJ Knutson C Hansen (Repository) S Hazle G Tunes de Silva, PhD M Arora, MD,MS* BA McGary KR Jackson P Hari, MD, MS A Nittala, BE, MS Program S Spellman, MS** P Mathur N Majhail, MD, MS* H Tian, MS Team CRCs Data Entry Specialist, LM Schneider M Pasquini, MD, MS X Zhang G Bruner Staff T Sobotka M Tomblyn, MD, MS* JM Dobratz CA Abel Administration SJ Lee, MD, MPH*** SW Ketelsen, MA IS Staff MK Desai C Jobe Director, A Prentice AS Kummerow Bioinformatics T Jaquot Study CRC DH Lindquist M Maiers DH Lindquist IRB, Associate Director KP Bhavsar MA Patel Associate Statistical Director AG Pereles of International Administration Programs KA Sobocinski, MS L Scott L Tharp DS Waldoch Benson, Imaging Informatics P Touchstone IRB CMP W Zhang L Williams M Young Associate Director of Development SL Fisher Program Biostatistics Prospective Data Management Monitoring & Auditing Associate Director RJ Drexler ME Matlack DA Christianson of Operations P Watry, RN, PAC Statistical Director Supervisor, Quality Control Sr Biostatistician II WS Pérez, MPH P Chitphakdiathai, PhD B Levesque-Olson M Ammi Program Biostatistician II M Haagenson, MS L Bellamy Associate Data Entry Coordinator II J Carreras, MPH Sr Developer KK Sullivan LTF Biostatistician I CATI Supervisor DM Burrows P Steinert, MBA A Hassebroek, MPH Biostatisticians Data Support E Iverson, MS Supervisor, M Agovi, MPH F Kan, MS, MA CATI Interviewer M Radtke Medical Writer Donor R Kanner M Chen, MS G Nelson Data Management Associates B Ventura, MA Quality Control Specialist II V He, PhD, MS SL Sorensen AE Hays Sr RA Krunkkala Program M Kukreja, MBBS, MPH Sr K Lawman Specialist Coordinator, S Shrestha, MS Specialist Data Entry Coordinators I Supervisor, L Wendland CM DeSutter SCTOD Z Wang, MS, MS TL Pedersen DM Fritz, JA Zarembinski K Delaney C Doleysh LE Horne Recipient Specialists KL Kutzner Data Management Program Sr SJ Czech M Miller KM Gardner Coordinator, Specialist Trial Init & AE Lund SA Tasky Accrual Management SC Mull AL Foley, MA, CCRP Imaging s * = University of Minnesota Sr Specialist TM Casillas ** = Also serves as Asst SM Flesch K Davis Scientific Director s N Gibitz Specialists s JG Lund SC Ewer *** = Fred Hutchinson Cancer Center JL Bloomquist NM Meissner M Radtke S Halvorson KL Bovy MI Nych = MKE Campus TM Thole SK Logan LJ Maserek M Ostanniy CJ Olson = MSP Campus Specialists JC Thompson = SCTOD Sub Contractors JI Clemons J Oakes, MA 2

3 268,000 Cases Registered, Publications Structure of the CW Bill Young Cell Transplantation Program Established by legislation passed in 2005 Department of Advisory Health and Human Council Services Transplan nts 270, , , , , , , , , , , ,000 90,000 75,000 60,000 45,000 30,000 15,000 0 Autologous QOL, Long-term Follow-up Allogeneic Multicenter Trials Immunobiology* * * Repository - Technology Assessment Specimens for >13,000 unrelated donor-recip pairs *SCTOD Repository Prognostic factors Related donor-recipient pairs Descriptive Pilot project in selected centers '84 '86 '88 '90 '92 '94 '96 '98 '00 '02 '04 '06 '08 Year 2008 numbers estimated Mmh07_2ppt Accrediting Organizations Infrastructure Public Interface HRSA Contract Organizations Other New Organizations or Relationships Cord Blood Banks Transplant Centers HRSA/Division of Transplantation Cord Blood Coordinating Center Single Point of Access / Office of Patient Advocacy Patients Stem Cell Therapeutic Outcomes Database Referring Physicians Bone Marrow Coordinating Center Under the Contract, SCTOD will- Collect data (and specimens) ALL allogeneic hematopoietic cell transplants (HCTs) with a recipient or donor from the US Related donor-recipient repository Other cellular therapies Quality of life data Secure, efficient electronic data capture system Analyze data Center-specific for US transplant centers Perform analyses of optimal size for the adult donor registry and cord blood unit inventory Conduct and support other research using the data collected under the contract Disseminate data Within the Program To the scientific and medical community To patients, families and the public EBMT Expanded MED-A MED-B Eurocord AP BMT Group Current/Future Data Flow Non-US; US Auto Voluntary AGNIS A Growable Network Information System: Collaboration with NIH Bioinformatics Transplant Essential Data Form Single Database ( Database) US Related*; Unrelated** Mandatory Comprehensive Report Forms Voluntary *Donor routinely collected **Donor to be collected on subset SCTOD ROLE OF OBSERVATIONAL DATABASE IN CLINICAL RESEARCH Analyze trends Descriptive studies Identify factors associated with outcome Center-specific Socioeconomic Biologic/genomic Assess treatments / strategies Donor selection Study late effects Analyze access / utilization Design / Interpret / Facilitate clinical trials From the bench to the bedside Preclinical Change in Basic Science/Animal Phase I Phase II Phase III Practice Model Better Outcomes PO1, RO1 Support 3

4 US Transplants on Cooperative Group Trials: Before the Other Large Multicenter HCT Trials in the 1990s funded by NHLBI f Transplants Number of Primarily (90%) autologous transplants Allo studies usually restricted to sibling transplants <3% of all HCTs, <1% allotransplants Focused on comparing HCT to non-hct therapy rarely addressed how to improve transplant T-cell depletion trial Phase III study comparing T-depleted and non-tdepleted unrelated donor transplants COBLT Phase II study of unrelated cord blood transplants Established: Sept 2001; renewed Oct Core Centers >50 Affiliate Centers 1 Data and Coordinating Center Goal of the Program: Provide the infrastructure needed to allow promising HCT therapies to be developed/evaluated in high quality multicenter studies Protocol Review Comm Committees NIH - NHLBI, NCI STEERING COMMITTEE Technical Committees Data and Coordinating Center //EMMES DSMB Protocol Teams 16 Core Centers Affiliate Centers Background Founded in 1977 Trial Support: Project Management, Data Management, Statistical Services Multi-stage, multiprotocol, multi-center Registry Support Information Technology Systems & Services About EMMES Vital Statistics Coordinated over 300 trials, registries & other research projects Involved over 150,000 participants Associated with medical institutions Over 300 staff; 40+ Statisticians 30+ IT professionals Specialists / Managers Systems Analysts staff Coordinating Center Support Biostatistical and scientific support Protocol Development EMMES AdvantageEDC Suite Web-based electronic data capture Real-time event monitoring/reporting i ti Data management, analysis, & reports GlobalTrace Quality assurance & protocol monitoring Regulatory support and reporting support 4

5 Experience in HCT T cell Depletion Trial (TCD) Cord Blood Banking and Transplantation Study (COBLT) Blood and Marrow Transplant Trials Network () Production Assistance for Cell-based Therapy (PACT Specialized Centers for Cell-Based Therapy (SCCT) RESPONSIBILITIES AND INTERACTIONS OF DCC MEMBERS Overall Coordination Scientific Leadership Medical Monitoring Statistical Design/ Analysis Electronic Communications Data Management Trial Oversight/ Protocol Monitoring Development/ Implementation Patient Advocacy Contracting Lab/ Repository Management EMMES DCC02_3ppt Collectively Administer DCC EMMES 2000 State of Science Symposium #1 sets scientific agenda for focus areas for HCT trials 1 Expanding donor/graft source 5 Decrease infections 2 Reduce regimen related toxicity 6 Improve late effects/qol 3 GVHD prevention/therapy 7 Rare diseases (added by Steering 4 Decrease relapse Committee and 2005 RFA 2007 State of Science Symposium #2 sets scientific agenda for Working Committees 11 high priority trials 4 in development (anticipated open date): Maintenance vs consol vs 2 nd Tx for MM 0702 (2009) Calcineurin-free inhibitors for CGVHD 0801 (2009) Reduced intensity tx for CLL 0804/CALGB lead (2009) Chemo vs HCT for Ph+ALL 0805/SWOG lead (2009) Note: See Appendix G of July 2008 Progress Report for list of all high-priority trials Early and ongoing collaboration with cooperative groups to synergize and avoid duplication (intensified since 2005) N of pts = 440 1,058 1,615 2,090 [2,500] [3,000] [3,600] [4,200] Foundation PII NST for NHL Governance and leadership Other trials to be opened in 2009 or later: 0604 PII Haplo in Adults Etblihd16C Established Core Centers 0602 Systemic Sclerosis allo-nmt (2009) 0603 PII Double CB in Adults Manual of Policies/procedures 0802 Phase III MMF for Acute GVHD (2009) 0601 PII Sickle Cell NST Electronic data capture system 0803 Allo-HCT in HIV with malignancies (2010) 0703 PII Hodgkin Disease Per patient reimbursement model 0704 PIII MM maintenance Websites for members & public 0403 PIII Etanercept for IPS Figure 1 ECOG CALBG Steering Comm SWOG COG LEGENDS = Enrollment complete = Enrollment on-going = Cumulative actual [projected] accrual = Coop group collaboration (see color key above) 0303 PII T-depleted HCT for AML 0302 PII AGVHD therapy 0202 PIII follicular NHL (closed early) 0102 PIII Myeloma Tandem HCT 0101 PIII Vori vs Fluconazole 0502 PII NST for AML >60y 0501 III Single vs Double CBT 0402 PIII GVHD prophylaxis 0301 PII Unrelated Tx for aplastic anemia 0401 PIII BEAM vs BEAM-Bexxar for Lymphoma 0201 PIII Unrelated PBSC vs Marrow TRIALS OPEN FOR ENROLLMENT, Transplants Number of US Transplants on Cooperative Group Trials: Impact of the % of transplants allotransplants >5% of US transplants both auto and allo >900 unrelated transplants (almost 10%) Cooperative Groups Total Resource for Investigations in BMT (RCI BMT) Builds on experience gained in coordinating the (and the ) but is NOT funded by the grant Formed to provide statistical expertise and data management services for multi-center t phase I/II trials Bridge the gap between single-center studies and the larger phase II/III studies supported by the Will partner with investigators to obtain necessary support for trial completion RCI BMT Trials Double cord blood transplants in adults: (9 centers activated; 11 patients accrued; Navy grant) Importance of KIR for transplant outcome (University of Minnesota PO1 responsible for donor specimen handling, IRB documentation) Related donor (RO1 awarded December 2008; PI: Michael Pulsipher) Revlimid maintenance after allotransplants for multiple myeloma (IRB approved contract with Celgene executed; centers being activated) Low Intensity Therapy and Reduced-Intensity Allogeneic Stem Cell Transplantation for MDS (Protocol in development) BUS06_27ppt 5

6 Impaired Health - low access, poor HCT in HCT: Roles of, SCTOD and Basic Biomedical new HCT drugs, strategies Human Studies of Safety/ Efficacy Science and Knowledge Practice and Health Decision Making Optimal HCT Treatment Effectiveness vs Efficacy who should vs does get HCT and why? Quality/ Access Improvement Improved Healthmore successful transplant s 6