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

. . .......................... ..... ...

. . ........................................... ...... ........... ......................................... . . . ......... ... ..

........ ... ... ......... .. ..... .......... ............................

.. .

. ..

. .

.....

.......

.. ... ....... . .........

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