Transplant Alphabet Soup –CIBMTR, NMDP, SCTOD, BMT
CTN, RCI BMT,……….
BUS06_1.ppt
Clinical ResearchClinical ResearchImpaired
Health
Basic Human Clinical Clinical Practice and Basic
Biomedical Research
Studies of Safety/Efficacy
Science and
Knowledge
Clinical Practice and Health Decision
Making
Improved Effecti eness Quality/ Improved Health
Effectiveness vs. Efficacy
Q y/Access
Improvement
From: Sung et al. Central challenges facing the national clinical research enterprise. JAMA 2003;289:1278-87.
Clinical Research in HCT: Roles of Impaired Clinical Research in HCT: Roles of BMT CTN, SCTOD and CIBMTR
Health - low access, poor
HCT outcomes
Basic Biomedical Human Studies Clinical Clinical Practice and
Health Decision Research –new HCT
drugs,strategies
Human Studies of Safety/Efficacy
Science and
Knowledge
Health Decision Making – Optimal
HCT Treatment
strategies
Improved Health-more
Effectiveness vs. Efficacy –who Quality/ more
successful transplant
s
should vs does get HCT and
why?
Q y/Access
Improvement
The CIBMTR Grew Out of Two Important The CIBMTR Grew Out of Two Important Collaborative Efforts in BMT
International Bone Marrow Transplant Registry (IBMTR)
National Ma o Dono National Marrow Donor Program (NMDP)
DBV06_22.ppt
IBMTRVoluntary outcomes registry established in 1970
2 years after the first successful HCTs At a time when there were ~ 12 t l t t 50 t l t transplant centers, < 50 transplants a year worldwide
Maintained a database of clinical information Maintained a database of clinical information on recipients of autologous and allogeneic hematopoietic stem cell transplants in ~450 p pcenters in 47 countries
Provided scientific and statistical support for
DBV06_23.ppt
analyzing those data
NMDP1986 – U.S. government appropriated funds to establish the National Bone Marrow Donor Registry (Donor Panel) 1988 – U.S. Organ Transplant Amendments
d d ll dAct – mandated collecting outcome data (Recipient Registry); also collects donor outcomesoutcomes~150 transplant centers and 90 donor centers Repository with matched recipient/donor blood samples
DBV06_24.ppt
CENTER FOR INTERNATIONAL BLOOD AND MARROW TRANSPLANT RESEARCHAND MARROW TRANSPLANT RESEARCH
Established July 2004Established July 2004
A research collaboration between the International Bone Marrow Transplant International Bone Marrow Transplant Registry and the National Marrow Donor Program to support clinical research in BMT Program to support clinical research in BMT & related fields
All of the former IBMTRAll of the former IBMTR
Research Operations Department of NMDPNMDP
NMDP
NMDP Research Operations
IBMTR
M di l Medical College of Wisconsin
NMDP
CIBMTR
M di l Medical College of Wisconsin
IBMTR – 1985 ( f fi j f di )(year of first major NIH funding)
1970-1985:
Mortimer M. Bortin, MD
Scientific Director
•200 centers•1,000 transplants•35 publications Sc e t c ecto
Al Rimm PhD
D’Etta WaldochSharon Meiers Karen GurgulAl Rimm, PhD
Statistician Diane Knutson Data
Management
gAdministrative
Asst
Location of Centers Participating in the CIBMTR 2009in the CIBMTR, 2009
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.....
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Chief Scientific DirectorMary M. Horowitz, MD, MS
Associate Scientific Director for Data OperationsJD Rizzo, MD, MS
ChiefStatistical Director
J Kl i PhD
Business ManagerSA Lorenz
AssociateScientific Directorfor CIBMTR-MSP
D Confer, MD
CIBMTR Organizational Structure
Programmers/Analysts
P Fen, MS, MSA Liu, MSB Li MS
Program Manager, Data Operations
TBA
Manager,Clinical Research
DJ K t
Medical Faculty
Sr Research AdvisorD Weisdorf, MD*
Associate Scientific Director
M Eapen, MD, MSAssistant Scientific
Directors
Manager,Clinical Research
SK M i
Director, IT H-J Khoo
J Klein, PhD
Statistical FacultyPhD Statisticians
K-W Ahn, PhDR Bajorunaite, PhD
B Logan, PhDT Wang, PhD
M-J Zhang, PhD
AssistantBusiness Manager
PA Vespalec
AdministrativeStaff
C FihnSL Finneran
D Confer, MD
Director,ScientificServices
M Setterholm
Sr Manager,ScientificServices
Vice-PresidentCIBMTR-MSPR King, MPH
Administrative SpecialistC HVi iti P f B Liu, MS
BA McGaryA Nittala, BE, MS
H Tian, MSX Zhang
Associate Directorof International
Associate Statistical Director
DJ KnutsonDirectorsM Arora, MD,MS*P Hari, MD, MS
N Majhail, MD, MS*M Pasquini, MD, MSM Tomblyn, MD, MS*SJ Lee, MD, MPH***
SK Meiers
Data Entry Staff
CA AbelMK Desai
AS KummerowDH Lindquist
MA PatelAG Pereles
Team CRCsG Bruner
JM DobratzSW Ketelsen, MA
A PrenticeStudy CRCKP Bhavsar
SL FinneranS Hazle
KR JacksonP Mathur
LM SchneiderT Sobotka
IS StaffT Jaquot
DH Lindquist
Director,Bioinformatics
M Maiers
Manager
(Repository)S Spellman, MS**
C Hansen
Program Specialist,Research
AdministrationC Jobe
Visiting ProfessorG Tunes de Silva, PhD
IRB Assistant,Research
Administration
Associate Directorof Development
SL Fisher
of International Programs
DS Waldoch Benson,CMP
KA Sobocinski, MS L ScottL Tharp
P TouchstoneL Williams
Associate Director
Sr Manager,Prospective Research
RJ Drexler
Manager,Clinical
InformaticsTBA
Program Manager, Monitoring & Auditing
DA Christianson
Sr Manager,Data Management
ME Matlack
Imaging AssistantW Zhang
IRB AssistantM Young
Sr Manager,Biostatistics
TBA
TBA
Assistant Statistical Director
WS Pérez, MPHBiostatistician IIJ Carreras, MPH
Program Manager,
LTFP Steinert, MBA
of OperationsP Watry, RN, PAC
BiostatisticiansM Agovi, MPHM Chen, MS
Supervisor, Clinical Research–Donor Data Management
SL S
Supervisor, Quality ControlB Levesque-OlsonBiostatistician II
P Chitphakdiathai, PhDM Haagenson, MS
Biostatistician IA Hassebroek, MPH
E Iverson, MSF Kan, MS, MA
G Nelson
Administrative AssistantL Bellamy
Sr Clinical Research AssociateKK Sullivan
Administrative AssistantM Ammi
CATI SupervisorTBA
Quality Control Specialist II
Data Entry Coordinator IIDM Burrows
CATI InterviewerR Kanner
Data Support AssistantM Radtke
Clinical Research
AssociatesAE H
Medical WriterB Ventura, MA
Sr Research DeveloperTBA
Sr Research Specialist
Program Coordinator,
BMT CTNSC Mull
Program Coordinator,
SCTODC Doleysh
,V He, PhD, MS
M Kukreja, MBBS, MPHS Shrestha, MS
Z Wang, MS, MS
ClinicalR h
SL Sorensen
Supervisor,Clinical Research,
Recipient Data Management
KM Gardner
Sr Clinical ResearchSpecialist
TL PedersenData Entry Coordinators I
DM FritzLE Horne
KL KutznerM Miller
TBA
Imaging AssistantsTM Casillas Clinical
ResearchClinical
ClinicalResearch SpecialistsSJ CzechAE LundSA Tasky
Sr Clinical Research Specialist
CM DeSutterK Delaney
Sr Clinical Research Specialist –Trial Init &Accrual ManagementAL Foley, MA, CCRP
Quality Control Specialist IIRA Krunkkala
* = University of Minnesota
AE HaysK Lawman
L WendlandJA Zarembinski
TBA
B Ventura, MA
OrgCht09_1.ppt
Sr Research SpecialistSM Flesch
Research Specialists
JL BloomquistKL Bovy
LJ MaserekCJ Olson
JC ThompsonClinical Research SpecialistsJI Clemons
J Oakes, MA
TM CasillasK DavisN GibitzJG LundM RadtkeTM Thole
ResearchAssistantsSC Ewer
S HalvorsonSK Logan
ResearchAssistants
NM MeissnerMI NychClinical Research
AssistantM Ostanniy
** = Also serves as CIBMTR Asst Scientific Director
*** = Fred Hutchinson Cancer Research Center= CIBMTR – MKE Campus= CIBMTR – MSP Campus= SCTOD – Sub Contractors
CIBMTR268,000 Cases Registered,1984-2008
270 000
268,000 Cases Registered,1984 2008415 Publications
195 000210,000225,000240,000255,000270,000
Autologous
AllogeneicQOL, Long-term Follow-up
Multicenter Clinical Trials
135,000150,000165,000180,000195,000
spla
nts
*NMDP Repository -
Multicenter Clinical Trials
Immunobiology*
60,00075,00090,000
105,000120,000
Tra
ns
*SCTOD Repository –
NMDP Repository Specimens for >13,000
unrelated donor-recip pairs Technology Assessment
Prognostic factors
015,00030,00045,00060,000
'84 '86 '88 '90 '92 '94 '96 '98 '00 '02 '04 '06 '08
Related donor-recipient pairs Pilot project in selected centers
Prognostic factors
Descriptive
'84 '86 '88 '90 '92 '94 '96 '98 '00 '02 '04 '06 '08
Year
Mmh07_2.ppt
2008 numbers estimated
Structure of the C.W. Bill Young Cell Transplantation Program –Established by legislation passed in 2005
AdvisoryDepartment of Advisory Council
HRSA/Division of
pHealth and Human
Services
Transplantation NMDP
Accrediting Organizations
Infrastructure
Cord Blood Banks
Cord Blood Coordinating
Center
Stem Cell Therapeutic Outcomes Database
Bone Marrow Coordinating
Center
Public Interface
CIBMTRSingle Point of Access /
Office of
T l ReferringHRSA ContractO i ti
CIBMTRPatient Advocacy
Transplant Centers
Referring Physicians
Organizations
Other New Organizations or
Relationships
Patients
Under the Contract, SCTOD will-
Collect data (and specimens)Collect data (and specimens)ALL allogeneic hematopoietic cell transplants (HCTs) with a recipient or donor from the U.S.Related donor-recipient repositoryRelated donor-recipient repositoryOther cellular therapiesQuality of life dataSecure efficient electronic data capture systemSecure, efficient electronic data capture system
Analyze dataCenter-specific outcomes for U.S. transplant centersPe fo m anal ses of optimal si e fo the ad lt dono egist Perform analyses of optimal size for the adult donor registry and cord blood unit inventoryConduct and support other research using the data collected under the contractunder the contract
Disseminate dataWithin the ProgramTo the scientific and medical communityTo the scientific and medical communityTo patients, families and the public
Current/Future Data FlowCurrent/Future Data Flow
Non-US; US Related*; EBMT
SCTOD
Transplant
Non-US;US Auto
US Related*; Unrelated**
Voluntary Mandatory
EBMT
ExpandedMED A Essential Data
Form
Comprehensive
MED-A
MED BAGNIS – A Growable Network
I f ti S t C ll b ti Report Forms
Voluntary
MED-B Information System: Collaboration with NIH Bioinformatics
Single CIBMTRDatabase (Research Database)
Eurocord
AP BMT Group
*Donor outcomes routinely collected**Donor outcomes to be collected on subset
ROLE OF OBSERVATIONAL DATABASE C C S CIN CLINICAL RESEARCH
Analyze trendsD i ti t diDescriptive studiesIdentify factors associated with outcome
ClinicalCenter-specificSocioeconomic Biologic/genomicBiologic/genomic
Assess treatments / strategies Donor selection
Study late effectsAnalyze access / utilizationDesign / Interpret / Facilitate clinical Design / Interpret / Facilitate clinical trials
From the bench to the bedside
Clinical Research Change inPreclinical Research Change in Practice –Better Outcomes
Basic Science/Animal Model Research
Phase I Phase II Phase III
PO1, RO1 Support
US Transplants on Cooperative Group i l f h CTrials: Before the BMT CTN
1200
1000
1200
nsp
lan
ts
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
600
800
ber
of
Tra
n Focused on comparing HCT to non-HCT therapy – rarely addressed how to improve transplant outcomes
200
400
Nu
mb
0
Other Large Multicenter HCT Trials in h 990 f d d bthe 1990s – funded by NHLBI
T-cell depletion trial – Phase III study T cell depletion trial Phase III study comparing T-depleted and non-T-depleted unrelated donor transplantsdepleted unrelated donor transplants
COBLT – Phase II study of unrelated d bl d t l tcord blood transplants
Established: Sept. 2001; renewed Oct. 200616 Core Centers>50 Affiliate Centers1 Data and Coordinating Center
Goal of the Program:Provide the infrastructure needed to allow promising HCT therapies to be d l d/ l t d i hi h lit lti tdeveloped/evaluated in high quality multicenter studies
NIH -
DSMB
NHLBI, NCIProtocol
Review
STEERING COMMITTEE
Comm
16 Core 16 Core Centers
AdministrativeCommittees
TechnicalCommittees Protocol
Teams
Data and Coordinating CenterCIBMTR/NMDP/EMMES
Affiliate Centers
About EMMES
• Background • Vital Statistics– Founded in 1977– Clinical Trial Support:
Project Management,
– Coordinated over 300 trials, registries & other research projectsInvolved over 150 000j g
Data Management, Statistical Services
– Multi-stage, multi-
– Involved over 150,000 participants
– Associated with 1000+ medical institutionsg
protocol, multi-center– Registry Support– Information Technology
medical institutions– Over 300 staff;
• 40+ Statisticians • 30+ IT professionalsInformation Technology
Systems & Servicesp
• Clinical Research Specialists / Clinical Research Managers
• Clinical Systems• Clinical Systems Analysts
• Administrative staff
Coordinating Center SupportCoordinating 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– Data management, analysis, & reports – GlobalTrace
• Quality assurance & protocol monitoringQuality assurance & protocol monitoring• Regulatory support and reporting• Administrative support• Administrative support
Experience in HCTExperience in HCT
• T cell Depletion Trial (TCD)• T cell Depletion Trial (TCD)• Cord Blood Banking and
Transplantation Study (COBLT)Transplantation Study (COBLT)• Blood and Marrow Transplant Clinical
Trials Network (BMT CTN)Trials Network (BMT CTN)• Production Assistance for Cell-based
Therapy (PACT Specialized Centers forTherapy (PACT Specialized Centers for Cell-Based Therapy (SCCT)
RESPONSIBILITIES AND INTERACTIONSINTERACTIONS
OF DCC MEMBERS
Overall Coordination Statistical
Design/
ElectronicCommunications
DataCIBMTR EMMES
Design/Analysis
Protocol Development/
Trial Oversight/Monitoring
Scientific Leadership
DataManagement
Development/ Implementation
Lab/Repository
ManagementMedical
Monitoring
NMDPPatient Advocacy
Contracting
DCC02_3.ppt
2000 State of Science Symposium #1 sets scientific agenda for 2001-2007 7 focus areas for HCT trials
2007 State of Science Symposium #2 sets scientific agenda for 2008-2012+ 12 Working Committees
1. Expanding donor/graft source 5. Decrease infections2. Reduce regimen related toxicity 6. Improve late effects/QOL3 GVHD ti /th 7 R di ( dd d b St i
11 high priority trials – 4 in development (anticipated open date):Maintenance vs consol vs 2nd Tx for MM – 0702 (2009)C l i i f i hibit f CGVHD 0801 (2009)
Collectively Administer
DCC
R S P3. GVHD prevention/therapy 7. Rare diseases (added by Steering 4. Decrease relapse Committee and 2005 RFA
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
2001 2002 2006 2007 2008 20102003 2004 2005 2011 20122009BMT CTN
Foundation
CIBM
TREM
MES
NMDP
N of pts = 440 1,058 1,615 2,090 [2,500] [3,000] [3,600] [4,200]Early and ongoing collaboration with cooperative groups to synergize and avoid duplication (intensified since 2005)
2001 2002
• Governance and leadership• Established 16 Core Centers• Manual of Policies/procedures• Electronic data capture system
P i i b d l
0601 PII Sickle Cell NST0703 PII Hodgkin Disease
0603 PII Double CB in Adults0604 PII Haplo in Adults
0701 PII NST for NHLOther 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)
0704 PIII MM maintenance
ECOG CALBGBMT CTNSteering
• Per patient reimbursement model• Websites for members & public
0402 PIII GVHD prophylaxis
0403 PIII Etanercept for IPS
0501 III Single vs Double CBT0502 PII NST for AML >60y
SWOG COG
SteeringComm 0301 PII Unrelated Tx for aplastic anemia
0303 PII T-depleted HCT for AML0401 PIII BEAM vs BEAM-Bexxar for Lymphoma
p p y
0302 PII AGVHD therapy0202 PIII follicular NHL (closed early)
= Enrollment completeE ll i
LEGENDS
0202 PIII follicular NHL (closed early)
0102 PIII Myeloma Tandem HCT0101 PIII Vori vs Fluconazole
0201 PIII Unrelated PBSC vs Marrow
TRIALS OPEN FOR ENROLLMENT, 2001-2008
= Enrollment on-going= Cumulative actual
[projected] accrual= Coop group collaboration
(see color key above)Figure 1
US Transplants on Cooperative Group Trials:p p pImpact of the BMT CTN
1200• 80% of BMT CTN transplants – allotransplants Total
800
1000
nsp
lan
ts
• 80% of BMT CTN transplants – allotransplants•>5% of US transplants – both auto and allo•>900 unrelated transplants (almost 10%)
Total
400
600
ber
of
Tra
n
BMT CTN
0
200Nu
mb
Cooperative Groups0
Resource for Clinical Investigations in BMT (RCI BMT)
Builds on experience gained in coordinating the p g gBMT 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 trialstrials.
Bridge the gap between single-center studies and the larger phase II/III studies supported by the the larger phase II/III studies supported by the BMT CTN
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); p ; y g )
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)2008; PI: Michael Pulsipher)
Revlimid maintenance after allotransplants for multiple myeloma (IRB approved – contract with u t p e ye o a ( app o ed co t act tCelgene executed; centers being activated)
Low Intensity Therapy and Reduced-Intensity Allogeneic Stem Cell Transplantation for MDS (Protocol in development)
BUS06_27.ppt
Clinical Research in HCT: Roles of Impaired Clinical Research in HCT: Roles of BMT CTN, SCTOD and CIBMTR
Health - low access, poor
HCT outcomes
Basic Biomedical Human Studies Clinical Clinical Practice and
Health Decision Research –new HCT
drugs,strategies
Human Studies of Safety/Efficacy
Science and
Knowledge
Health Decision Making – Optimal
HCT Treatment
strategies
Improved Health-more
Effectiveness vs. Efficacy –who Quality/ more
successful transplant
s
should vs does get HCT and
why?
Q y/Access
Improvement