CCO_NMDP_2009_Confer_骨髓移植

nullAdvances in AML/MDS: The Role of Multicenter Clinical Trials Advances in AML/MDS: The Role of Multicenter Clinical Trials Dennis L. Confer, MD Chief Medical Officer, NMDPAbout These SlidesAbout These SlidesOur thanks to the presenters who gave permission to include their original data Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent These slides may not be published or posted online without permission from Clinical Care OptionsDisclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.Annual Numbers of Blood and Marrow Transplantations, 1970-2006 - Worldwide -*Annual Numbers of Blood and Marrow Transplantations, 1970-2006 - Worldwide -Number of TransplantsCurrent Annual Activity Estimates – Worldwide – *Current Annual Activity Estimates – Worldwide – Autologous transplants ~40,000 annually Allogeneic transplants ~25,000 annually More than half of allogeneic transplants use unrelated donor products More than 14 million adult donors are registered worldwide The world’s inventory of unrelated donor (i.e., public) umbilical cord blood units exceeds 400,000null*National Marrow Donor Program Adult Donors & Cord Blood Units – Oct, 2009Adult Donors 8,013,658CBUs 114,500NMDP Transplants Facilitated by Fiscal Year 1987–2009*NMDP Transplants Facilitated by Fiscal Year 1987–2009Cord blood Peripheral blood stem cells Bone marrowNMDP Minority Transplants by FY 2007–2009*NMDP Minority Transplants by FY 2007–2009Cord blood Adult donors23%14%191364244438328450NMDP Transplant Recipients by Diagnosis – Selected Malignancies*NMDP Transplant Recipients by Diagnosis – Selected Malignancies NMDP Transplant Recipients by Age – By Fiscal Year 2006 - 2009*NMDP Transplant Recipients by Age – By Fiscal Year 2006 - 2009 NMDP Transplant Recipients by Age – By Fiscal Year 2006 - 2009*NMDP Transplant Recipients by Age – By Fiscal Year 2006 - 2009 685845RationaleSlide *Rationalewww. bmtctn.netnullSlide *Established: Sept. 2001; renewed Oct. 2006 16 Core Center cooperative agreements 1 DCC cooperative agreement: CIBMTR with subcontracts to NMDP & EMMES Goal of the Program: Provide the infrastructure needed to allow promising HCT therapies to be developed/evaluated in high quality multicenter studies nullSlide *Slide *200120022006200720082010200320042005201120122009BMT CTN FoundationCollectively Administer DCC2007 State of Science Symposium #2 Sets scientific agenda for 2008-12+  12 Working Committees N of pts = 440 1,058 1,615 2,090 2,500 [3,000] [3,600] [4,200] Governance and leadership Established 16 Core Centers Manual of Policies/procedures Electronic data capture system Per patient reimbursement model Websites for members & publicExpanding donor/graft source 5. Decrease infections Reduce regimen related toxicity 6. Late effects/QOL GVHD prevention/therapy 7. Rare diseases Decrease relapse Early and ongoing collaboration with cooperative groups to synergize and avoid duplication (intensified since 2005)11 high priority trials – 6 in development: 1. Maint vs consol vs 2nd Tx for MM 2. Calcineurin-inhibitor-free Rx for CGVHD 3. Reduced intensity tx for CLL 4. Chemo vs HCT for Ph+ ALL 5. Reduced vs standard intensity conditioning 6. Peritransplant QOL2000 State of Science Symposium #1 -Set scientific agenda for 2001-07  7 focus areas for HCT trialsN of trials = 2 4 6 9 13 18 [22] [27] [32]BMT CTN Centers, 2009 >70 centers have enrolled >3,000 patients since 2003Slide *Mmh06_16.pptBMT CTN Centers, 2009 >70 centers have enrolled >3,000 patients since 2003Blood and Marrow Transplant Clinical Trials Network – BMT CTNSlide *Blood and Marrow Transplant Clinical Trials Network – BMT CTN10 Trials completed accrual Unrelated donor PBSC v. Bone Marrow – 551 donor-recipient pairs T-cell depletion for AML – 47 recipients 8 Trials are enrolling Prevention of acute GvHD Single v. double umbilical cord blood Haploidentical NST Umbilical cord blood NST 8 Trials are in development nullSlide *Endpoints in PBSC v. Marrow TrialSlide *Endpoints in PBSC v. Marrow TrialRecipients 2-year survival 3-year survival, engraftment, graft failure, GvHD, relapse, infections Immune reconstitution Quality of life Donors Donation-related experiences Long-term follow-up Quality of life Accrual to PBSC v. Marrow – 60 MonthsSlide *Accrual to PBSC v. Marrow – 60 MonthsBlood and Marrow Transplant Clinical Trials Network – BMT CTNSlide *Blood and Marrow Transplant Clinical Trials Network – BMT CTN10 Trials completed accrual Unrelated donor PBSC v. Bone Marrow – 551 donor-recipient pairs T-cell depletion for AML – 47 recipients 8 Trials are enrolling Single v. double umbilical cord blood Prevention of acute GvHD Haploidentical NST Umbilical cord blood NST 8 Trials are in development Accrual to 0603 – Haploidentical NSTSlide *Accrual to 0603 – Haploidentical NSTAccrual to 0604 – Cord Blood NSTSlide *Accrual to 0604 – Cord Blood NSTBMT CTN Yearly and Cumulative Accrual to All Protocols, 2004 - mid-June 2009Slide *BMT CTN Yearly and Cumulative Accrual to All Protocols, 2004 - mid-June 20098 Protocols Anticipated to Open in 2009-2010 Slide *8 Protocols Anticipated to Open in 2009-2010 0702 – Myeloma – At IRBs 0801 – Chronic GVHD – At IRBs 0802 – Acute GVHD – At IRBs 0803 – HIV+ Lymphoma – Submitted to PRC 0804 – Peripheral T-Cell NHL: CALGB 0805 – Ph+ ALL: SWOG 0805 0901 – NST vs myeloablative – In development 0902 – Stress Reduction – Submitted to PRC US Transplants on Cooperative Group Trials: Impact of the BMT CTNSlide *US Transplants on Cooperative Group Trials: Impact of the BMT CTNNumber of Transplants 80% of BMT CTN transplants – allotransplants >5% of US transplants – both auto and allo >900 unrelated transplants (almost 10%)Cooperative GroupsBMT CTNTotalnullAnn Arbor, Michigan June 7-8, 2007BMT CTN 0901: A Multi-center Phase III Study Comparing Myeloablative to Nonmyeloablative Transplantation in Patients with Myelodysplastic Syndrome or Acute Myelogenous LeukemiaBMT CTN 0901: A Multi-center Phase III Study Comparing Myeloablative to Nonmyeloablative Transplantation in Patients with Myelodysplastic Syndrome or Acute Myelogenous LeukemiaBMT CTN Steering Committee Meeting October 2009Reduced versus Conventional Intensity Conditioning in Patients Age 30-60 with AML in CRSlide *Reduced versus Conventional Intensity Conditioning in Patients Age 30-60 with AML in CRHypothesis Reduction in transplant-related mortality will be less than any increase in relapse rates associated with reduced intensity conditioning. DFS will increase.Proposed Trial Design for 0901Proposed Trial Design for 0901Advanced MDS/ AML< 5% blasts2 year SurvivalPatients randomizedRIC regimens1 Flu/BU* Flu/Mel MA Regimens Bu*/Flu Bu*/Cy Cy/TBIGVHD Prophylaxis T-cell replete per Institutional guidelines* IV or PO Bu1Bu <8mg/kg Mel <150mg/m2Proposed Phase III AML Clinical TrialSlide *Proposed Phase III AML Clinical TrialProposal: Unrelated donor transplant versus chemotherapy for high risk AMLCan transplant from unrelated donors improve AML patient survival when compared to non-transplant therapies?Concept of a Study DesignSlide *Concept of a Study DesignInclude: AML, 18-60 yrs, high-risk cytogenetics Genetic assignment between allogeneic transplant (related & unrelated) and no transplant Must survive minimum time frame Total AML enrolled: N = 2000 Unrelated Donor: N ~ 216 No Donor: N ~ 120 Endpoint: Survival at 3 years. Power: 80% to detect a 15% difference. Selection of High-Risk AML Patients Based on CytogeneticsSlide *Selection of High-Risk AML Patients Based on CytogeneticsLogistics and FeasibilitySlide *Logistics and FeasibilityRequires Intergroup collaboration Requires timely cytogenetics testing, HLA typing and donor search DNA-based high-resolution HLA typing at diagnosis Facilitated search of NMDP registry – NMDP’s process improvement initiative NMDP Transplants Facilitated and Projected to 2015*NMDP Transplants Facilitated and Projected to 2015Cord blood Peripheral blood stem cells Bone marrowThe Needs and the Barriers*The Needs and the BarriersThere are at least 10,000 U.S. candidates annually for unrelated donor transplantation NMDP has set a goal of 10,000 transplants in 2015 (perhaps 8,000 of these would be in the U.S.) Barriers to meeting this goal, include referral timing, graft availability, financial issues, space and personnel shortages, etc. One of the most significant barriers, however, is having the processes and systems that can support this level of activity The Phoenix Initiative*The Phoenix InitiativeAn effort to transform the way we operate and manage the donor and patient processes Provide more and better information Provide quicker and better access to the worldwide pool of donors and cord blood units Provide more predictability, reduce the pain of Unavailable donors Untimely results Surprises and last minute “revelations” Meet the transplant center’s timelineChanges to the Process*Changes to the ProcessPut all the donors and all the CBUs in a single view Merge the NMDP, Cooperative Registry and BMDW lists Provide information on DC, CBB or coop registry identity and performance Implement a “donor readiness” score Pre-contact adult donors who are on the search Facilitate communication between TCs and DC/CBB Reduce paper, increase e-communications, and increase viewability of online search-related documents Summary and Conclusions*Summary and ConclusionsMany critical questions in transplantation can only be addressed in multicenter clinical trials BMT CTN in collaboration with the cancer cooperative groups provides a structure for answering complex questions The availability of alternative donors – unrelated adult, umbilical cord blood units and mismatched family members – extends transplant options to most potential candidates To optimize the use of alternative donors and meet the growing demand, new approaches for search and donor management are needed Go Online for More Information on Allogeneic Transplantation!Go Online for More Information on Allogeneic Transplantation!Virtual Presentations on advances in risk stratification, role of ASCT in AML, options for high-risk AML and MDS patients, and ongoing and planned clinical trials for transplantation. 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