Transplant Alphabet Soup CIBMTR, NMDP, SCTOD, BMT CTN, RCI BMT,. BUS06_1.ppt

Transcription

1 Transplant Alphabet Soup CIBMTR, NMDP, SCTOD, BMT CTN, RCI BMT,. BUS06_1.ppt

2 Impaired Health Clinical Research Basic Biomedical Research Human Studies of Safety/ Efficacy Clinical Science and Knowledge Clinical Practice and Health Decision Making Effectiveness eness vs. Efficacy Quality/ Access Improvement Improved Health From: Sung et al. Central challenges facing the national clinical research enterprise. JAMA 2003;289:

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

4 The CIBMTR Grew Out of Two Important Collaborative Efforts in BMT International Bone Marrow Transplant Registry (IBMTR) National Marrow Donor Program (NMDP) DBV06_22.ppt

5 IBMTR Voluntary outcomes registry established in years after the first successful HCTs At a time when there were ~ 12 transplant t centers, < 50 transplants t 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 DBV06_23.ppt

6 NMDP 1986 U.S. government appropriated funds to establish the National Bone Marrow Donor Registry (Donor Panel) 1988 U.S. Organ Transplant Amendments Act mandated d collecting outcome data (Recipient Registry); also collects donor outcomes ~150 transplant centers and 90 donor centers Repository with matched recipient/donor blood samples DBV06_24.ppt

7 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 Research Operations Department of NMDP

8 NMDP NMDP Research Operations IBMTR Medical College of Wisconsin

9 NMDP CIBMTR Medical College of Wisconsin

10 IBMTR 1985 (year of first major NIH funding) : 200 centers 1,000 transplants 35 publications Mortimer M. Bortin, MD Scientific c Director Al Rimm, PhD Statistician D Etta Waldoch Sharon Meiers Diane Knutson Data Management Karen Gurgul Administrative Asst

11 Location of Centers Participating in the CIBMTR,

12 Chief Scientific Director Mary M. Horowitz, MD, MS CIBMTR Organizational Structure Business Manager SA Lorenz Chief Statistical Director JKl Klein, PhD Associate Scientific Director for Data Operations JD Rizzo, MD, MS AssociateScientific Director for CIBMTR-MSP D Confer, MD Assistant Business Manager PA Vespalec Administrative Staff C Fihn SL Finneran S Hazle KR Jackson P Mathur LM Schneider T Sobotka Associate Director of International Programs DS Waldoch Benson, CMP Associate Director of Development SL Fisher Associate Director of Operations P Watry, RN, PAC Program Manager, LTF P Steinert, MBA Medical Writer B Ventura, MA Program Coordinator, SCTOD C Doleysh Program Coordinator, BMT CTN SC Mull Statistical Faculty Medical Faculty PhD Statisticians Sr Research Advisor K-W Ahn, PhD D Weisdorf, MD* R Bajorunaite, PhD Associate Scientific B Logan, PhD Programmers/ Director T Wang, PhD Analysts M Eapen, MD, MS M-J Zhang, PhD P Fen, MS, MS Assistant Scientific A Liu, MS Visiting iti Professor Directors BLi Liu, MS G Tunes de Silva, PhD BA McGary A Nittala, BE, MS H Tian, MS X Zhang Associate Statistical Director KA Sobocinski, MS Assistant Statistical Director WS Pérez, MPH Biostatistician II J Carreras, MPH Biostatisticians M Agovi, MPH M Chen, MS V He, PhD, MS M Kukreja, MBBS, MPH S Shrestha, MS Z Wang, MS, MS M Arora, MD,MS* P Hari, MD, MS N Majhail, MD, MS* M Pasquini, MD, MS M Tomblyn, MD, MS* SJ Lee, MD, MPH*** Biostatistician II P Chitphakdiathai, PhD M Haagenson, MS Biostatistician I A Hassebroek, MPH E Iverson, MS F Kan, MS, MA G Nelson Sr Clinical Research Specialist TL Pedersen * = University of Minnesota ** = Also serves as CIBMTR Asst Scientific Director *** = Fred Hutchinson Cancer Research Center = CIBMTR MKE Campus = CIBMTR MSP Campus = SCTOD Sub Contractors Sr Manager, Biostatistics TBA IS Staff T Jaquot DH Lindquist Director, IT H-J Khoo Program Manager, Data Operations TBA Manager, Clinical Research SK Meiers Team CRCs G Bruner JM Dobratz SW Ketelsen, MA A Prentice Study CRC KP Bhavsar Sr Manager, Prospective Research RJ Drexler Administrative Assistant L Bellamy CATI Supervisor TBA CATI Interviewer R Kanner Sr Clinical Research Specialist CM DeSutter K Delaney Sr Clinical Research Specialist Trial Init & Accrual Management AL Foley, MA, CCRP Sr Research Specialist SM Flesch Clinical Research Assistant M Ostanniy Imaging Assistant W Zhang Manager, Clinical Research DJ Knutson Data Entry Coordinator II DM Burrows Data Support Assistant M Radtke Quality Control Specialist II RA Krunkkala Data Entry Coordinators I DM Fritz LE Horne KL Kutzner M Miller TBA Imaging Assistants TM Casillas K Davis N Gibitz JG Lund M Radtke TM Thole Clinical Research Specialists JI Clemons J Oakes, MA Data Entry Staff CA Abel MK Desai AS Kummerow DH Lindquist MA Patel AG Pereles L Scott L Tharp P Touchstone L Williams Supervisor, Quality Control B Levesque-Olson Administrative Specialist CH Hansen Program Specialist, Research Administration C Jobe IRB Assistant, Research Administration TBA IRB Assistant M Young Sr Manager, Data Management ME Matlack Supervisor, Clinical Research, Recipient Data Management KM Gardner Clinical Research Assistants SC Ewer S Halvorson SK Logan Vice-President CIBMTR-MSP R King, MPH Administrative Assistant M Ammi Sr Research Developer TBA Supervisor, Clinical Research Donor Data Management SL Sorensen Clinical Research Specialists JL Bloomquist KL Bovy LJ Maserek CJ Olson JC Thompson Director, Scientific Services M Setterholm Sr Manager, Scientific Services (Repository) S Spellman, MS** Director, Bioinformatics M Maiers Manager, Clinical Informatics TBA Program Manager, Monitoring & Auditing DA Christianson Clinical Research Specialists SJ Czech AE Lund SA Tasky Clinical Research Assistants NM Meissner MI Nych Sr Clinical Research Associate KK Sullivan Clinical Research Associates AE Hays K Lawman L Wendland JA Zarembinski TBA OrgCht09_1.ppt

13 CIBMTR 268,000 Cases Registered, Publications Trans splants 270, , , , , , , , , , , ,000 90,000 75,000 60,000 45,000 30,000 15,000 0 Autologous Allogeneic QOL, Long-term Follow-up Multicenter Clinical Trials Immunobiology* Technology Assessment Prognostic factors Descriptive *NMDP Repository - Specimens for >13,000 unrelated donor-recip pairs *SCTOD Repository Related donor-recipient pairs Pilot project in selected centers '84 '86 '88 '90 '92 '94 '96 '98 '00 '02 '04 '06 '08 Year 2008 numbers estimated Mmh07_2.ppt

14 Structure of the C.W. Bill Young Cell Transplantation Program Established by legislation passed in 2005 Department of Health and Human Services Advisory Council HRSA/Division of Transplantation NMDP Accrediting Organizations Infrastructure Cord Blood Banks Cord Blood Coordinating Center Stem Cell Therapeutic Outcomes Database Bone Marrow Coordinating Center Public Interface Single Point of Access / Office of Patient Advocacy CIBMTR HRSA Contract Organizations Other New Organizations or Relationships Transplant Referring Centers Physicians Patients

15 Under the Contract, SCTOD will- Collect data (and specimens) ALL allogeneic hematopoietic cell transplants (HCTs) with a recipient or donor from the U.S. Related donor-recipient repository Other cellular therapies Quality of life data Secure, efficient electronic data capture system Analyze data Center-specific outcomes for U.S. 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

16 Current/Future Data Flow SCTOD EBMT Non-US; US Auto US Related*; Unrelated** Expanded MED-A Voluntary Transplant Essential Data Form Mandatory MED-B AGNIS A Growable Network Comprehensive Information System: Collaboration Report Forms with NIH Bioinformatics Voluntary Eurocord AP BMT Group Single CIBMTR Database (Research Database) *Donor outcomes routinely collected **Donor outcomes to be collected on subset

17 ROLE OF OBSERVATIONAL DATABASE IN CLINICAL C RESEARCH Analyze trends Descriptive studies Identify factors associated with outcome Clinical Center-specific Socioeconomic Biologic/genomic Assess treatments / strategies Donor selection Study late effects Analyze access / utilization Design / Interpret / Facilitate clinical trials

18 From the bench to the bedside Preclinical Research Basic Science/Animal Model Research PO1, RO1 Support Clinical Research Phase I Phase II Phase III Change in Practice Better Outcomes

19 US Transplants on Cooperative Group Trials: Before the BMT CTN Numb ber of Tran nsplants 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 outcomes

20 Other Large Multicenter HCT Trials in the 1990s funded d by NHLBI T-cell depletion trial Phase III study comparing T-depleted and non-t- depleted unrelated donor transplants COBLT Phase II study of unrelated cord blood transplants t

21 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 d/ l d in high h quality multicenter t studies

22 Protocol Review Comm NIH - NHLBI, NCI DSMB STEERING COMMITTEE 16 Core Centers Administrative Committees Technical Committees Protocol Teams Data and Coordinating Center CIBMTR/NMDP/EMMES Affiliate Centers

23 About EMMES Background Founded in 1977 Clinical Trial Support: Project Management, Data Management, Statistical Services Multi-stage, multiprotocol, multi-center Registry Support Information Technology Systems & Services Vital Statistics Coordinated over 300 trials, registries & other research projects Involved over 150, participants Associated with medical institutions Over 300 staff; 40+ Statisticians 30+ IT professionals Clinical Research Specialists / Clinical Research Managers Clinical Systems Analysts Administrative staff

24 Coordinating Center Support Biostatistical and scientific support Protocol Development EMMES AdvantageEDC Suite Web-based electronic data capture Real-time event monitoring/reporting Data management, analysis, & reports GlobalTrace Quality assurance & protocol monitoring Regulatory support and reporting Administrative support

25 Experience in HCT T cell Depletion Trial (TCD) Cord Blood Banking and Transplantation Study (COBLT) Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Production Assistance for Cell-based Therapy (PACT Specialized Centers for Cell-Based Therapy (SCCT)

26 RESPONSIBILITIES AND INTERACTIONS OF DCC MEMBERS CIBMTR Overall Coordination Scientific Leadership Medical Monitoring Electronic Statistical Communications Design/ Data Analysis Management Trial Oversight/ Protocol Monitoring Development/ Implementation Lab/ Repository Management EMMES Patient Advocacy Contracting NMDP DCC02_3.ppt

27 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 dby Steering 4. Decrease relapse Committee and 2005 RFA Collectively Administer DCC 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 i 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 CIBMTR EMMES NMDP BMT CTN Foundation Governance and leadership Established 16 Core Centers Manual of Policies/procedures Electronic data capture system Per patient reimbursement model Websites for members & public Figure 1 ECOG CALBG BMT CTN Steering Comm SWOG COG LEGENDS = Enrollment complete 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] = Enrollment on-going = Cumulative actual [projected] accrual = Coop group collaboration (see color key above) Other trials to be opened in 2009 or later: 0602 Systemic Sclerosis allo-nmt (2009) 0802 Phase III MMF for Acute GVHD (2009) 0803 Allo-HCT in HIV with malignancies (2010) 0701 PII NST for NHL 0604 PII Haplo in Adults 0603 PII Double CB in Adults 0601 PII Sickle Cell NST 0703 PII Hodgkin Disease 0704 PIII MM maintenance 0403 PIII Etanercept for IPS 0502 PII NST for AML >60y 0501 III Single vs Double CBT 0402 PIII GVHD prophylaxis p 0301 PII Unrelated Tx for aplastic anemia 0401 PIII BEAM vs BEAM-Bexxar for Lymphoma 0303 PII T-depleted HCT for AML 0302 PII AGVHD therapy 0202 PIII follicular NHL (closed early) 0201 PIII Unrelated PBSC vs Marrow 0102 PIII Myeloma Tandem HCT 0101 PIII Vori vs Fluconazole TRIALS OPEN FOR ENROLLMENT,

28 US Transplants on Cooperative Group Trials: Impact of the BMT CTN Numb ber of Tran nsplants % of BMT CTN transplants allotransplants >5% of US transplants both auto and allo >900 unrelated transplants (almost 10%) Cooperative Groups BMT CTN Total

29 Resource for Clinical Investigations in BMT (RCI BMT) Builds on experience gained in coordinating the BMT CTN (and the CIBMTR) but is NOT funded by the BMT CTN grant Formed to provide statistical expertise and data management services for multi-center phase I/II trials. Bridge the gap between single-center studies and the larger phase II/III studies supported by the BMT CTN Will partner with investigators to obtain necessary support for trial completion.

30 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 outcomes (RO1 awarded December 2008; PI: Michael Pulsipher) Revlimid maintenance after allotransplants for multiple utpemyeloma yeo a( (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_27.ppt

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