[ Visit Client Website ]

Before you can access ASH's online program, you must agree to the following:
  • Abstracts submitted to the ASH Annual Meeting are considered embargoed from the time of submission.
  • The media, companies and institutions issuing press releases, and others are required to abide by the embargo policies governing the Society’s annual meeting. Read ASH’s embargo policy for more information.

3803 The Multiple Myeloma Research Consortium (MMRC) Model: Reduced Time to Trial Activation and Improved Accrual Metrics

Program: Oral and Poster Abstracts
Session: Health Services and Outcomes Research: Poster III
Monday, December 6, 2010, 6:00 PM-8:00 PM
Hall A3/A4 (Orange County Convention Center)
Poster Board III-582

Sandra Wear, RN1*, Paul G. Richardson, MD2, Carolyn Revta, MPH3*, Ravi Vij, MBBS, MD4, Mark Fiala, BS, CCRP5*, Sagar Lonial, MD6, Dixil Francis, MPH, CCRC7*, David S. Siegel, MD, PhD 8, Alex Schramm, BA9*, Andrzej J. Jakubowiak, MD, PhD10, Colleen K. Harvey10*, Donna E. Reece, MD, FRCPC11, Engin Gul, HonBSc12*, Sundar Jagannath, MD13*, Lisa La, MS14*, Craig C. Hofmeister, MD15, Buffy Jansak, BSN, OCN15*, Keith Stewart, MBA, MB, CHB16, Rachel Hagerty17*, Jeffrey L. Wolf, MD18*, Beth Davis19*, Amrita Krishnan, MD20, Lupe Duarte, CCRC20*, Todd M. Zimmerman, MD21, Angela Cisneros21*, Shaji Kumar, MD22, Ann Birgin, CRA23*, Robert Ott, MBA1*, Leah Tasca, BA24*, Susan L. Kelley, MD1, Kenneth C. Anderson, MD25 and Kathy Giusti, MBA26*

1Multiple Myeloma Research Consortium, Norwalk, CT
2Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
3Dana-Farber Cancer Institute, Boston, MA
4Division of Oncology, Washington University School of Medicine, Saint Louis, MO
5Division of Oncology, Washington University School of Medicine, St. Louis, MO
6Winship Cancer Institute of Emory University, Atlanta, GA
7Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA
8John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ
9The John Theurer Cancer Center Hackensack Univ. Med. Ctr., Hackensack, NJ
10University of Michigan, Ann Arbor, MI
11Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada
12University Health Network, Princess Margaret Hospital, Toronto, ON, Canada
13Mount Sinai Medical Center, New York, NY
14Mount Sinai School of Medicine, New York, NY
15Internal Medicine, Division of Hematology, The Ohio State University Medical Center, Columbus, OH
16Research, Mayo Clinic, Scottsdale, AZ
17Mayo Clinic, Scottsdale, AZ
18University of California, San Francisco, San Francisco, CA
19Hematology/Blood and Marrow Transplant, University of California San Francisco, San Francisco, CA
20Hematology and Stem Cell Transplantation, City of Hope, Duarte, CA
21University of Chicago Medical Center, Chicago, IL
22Division of Hematology, Mayo Clinic, Rochester, MN
23Mayo Clinic, Rochester, MN
24The Multiple Myeloma Research Consortium, Norwalk, CT
25The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
26Multiple Myeloma Research Foundation, Norwalk, CT

Background:  The MMRC is a non-profit, disease-focused consortium founded in 2004 comprised of 13 North American centers with expertise in multiple myeloma (MM).  The MMRC Inc. (Norwalk, CT), MMRC’s member institutions, and several pharmaceutical partners work closely to speed early development of new treatment options for MM patients.  In December 2007, MMRC headquarters staff implemented multiple project management (PM) business solutions to address trial barriers that delay activation of our phase I-II clinical trials and established trial metric benchmarks considered attainable at our member institutions.   In November 2009, we reported initial data1  on trial activation:  MMRC trials initiated between Sep08-Jul09 (n=5) demonstrated a 38% decrease in mean time to first patient dosed (FPFD), compared with the Early Group trials (EG) initiated before PM solutions (Jun06-Sept08; n=7 trials). These results also confirmed improvement over published metrics from Dilts et al 2,3 . We present additional data on time to FPFD and now enrollment, to assess impact of the MMRC PM resources and processes on trial efficiency.  

Methods: Twenty-one (21) trials conducted within the MMRC from May 2006 to June 2010 had sufficient trial data for review.  Data were collected by MMRC-funded project managers at the clinical centers using a web-based clinical trial management system (CTMS).  FPFD was defined as the time from the member institutions’ receipt of the final protocol (FP) from the trial sponsor, to the time the first patient was dosed on the trial at any participating MMRC member institution.  With respect to enrollment, pre-study enrollment commitment (EC) established between MMRC and the study sponsor was defined as the total number of subjects committed to receive at least one dose of study drug across all participating MMRC centers on a trial; baseline enrollment timeline (BET) was prospectively defined as the target time period to attain EC.

Results:  Mean time to FPFD was 181 calendar days for the early group trials (EG, n=7) and 122 days for the recent group (RG) trials (n=14, Sep08 – Jun10), representing a 32% reduction of time to FPFD in the RG.  Additionally, time from final protocol to first patient dosed at all MMRC centers on a trial decreased 18% from a mean of 7.7 months (EG) to 6.3 months (RG).  With respect to MMRC trial enrollment, data was available for 16/21 trials (5 EG and 11 RG).  2 EG trials were missing data and 3 RG trials were still enrolling as of June 2010. The mean MMRC pre-study EC was 39 subjects per trial (n=16 trials; 626 enrollment target); the mean actual MMRC enrollment was 49 subjects per trial (n=16; 783 enrolled through Jun 29, 2010) representing a 25% increase in actual versus committed enrollment.  Two trials did not meet MMRC EC: MMRC investigators discontinued their involvement in these trials at approximately 30% target EC due to trial complexity or low patient enrollment.  14/16 evaluable trials (88%) met their EC; 11/16 trials met EC within BET (69%) of which 8/16 trials (50%) reached EC 34% faster than their BET (representing a mean reduction of 4.5 months).  The overall pre-study mean BET for 16 trials was 13.1 months.  MMRC’s actual mean enrollment timeline was 11.3 months for the group of 14 evaluable trials representing improvement over the original BET by a mean of 1.9 months (14%).  We believe FP to FPFD is a more meaningful metric beyond that of first patient consented.  Moreover, we believe that if all participating trial centers focus their efforts on dosing the first patient and within a targeted timeframe, it may improve our research efforts overall. 

Conclusion: Development of drugs in the clinical setting has become time and resource intensive. Activating and enrolling trials promptly is a priority for drug development.  The MMRC’s standardization of processes and support for site-based PM resources results in improved trial metrics.  MMRC member centers met or exceeded pre-specified enrollment targets in 88% of the trials analyzed to date.  Ongoing monitoring of trial conduct continues to reveal areas where increased focus is needed to realize further trial efficiencies.  These trial metrics and measures to improve efficiency may be applied with similar expected benefit in all oncology disciplines.  

1. Wear S et al. Proc AACR-NCI-EORTC International Conference, Boston, Nov. 2009 (Abstract # B58).

2. Dilts DM, Sandler AB. J Clin Oncol. 2006 24(28): 4545-52.

3. Dilts DM et al. J Clin Oncol. 2006 24(28): 4553-7.

Disclosures: Wear: Multiple Myeloma Research Consortium (MMRC): Employment. Richardson: Novartis: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees; Millennium: Membership on an entity’s Board of Directors or advisory committees; Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Johnson & Johnson: Membership on an entity’s Board of Directors or advisory committees. Revta: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Vij: Multiple Myeloma Research Consortium (MMRC): Research Funding; Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Fiala: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Lonial: Novartis Pharmaceuticals: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Millenium Pharmaceuticals Inc: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene Corporation: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Bristo-Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Onyx: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Francis: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Siegel: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Celgene: Speakers Bureau; Millennium: Speakers Bureau. Schramm: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Jakubowiak: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC, Research Funding; Millennium: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Centocor Ortho-Biotech: Honoraria, Speakers Bureau; Exelixis: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Harvey: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Reece: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Celgene: Honoraria, Research Funding; Ortho Biotech: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Facet: Research Funding; Otsuka: Honoraria, Research Funding. Gul: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Jagannath: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Proteolix: Honoraria; Merck: Honoraria; Onyx Pharma: Honoraria; Orthobiotec: Honoraria; Millenium: Honoraria; Celgene: Honoraria. La: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Hofmeister: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Jansak: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Stewart: Celgene: Honoraria; Millennium: Consultancy; Multiple Myeloma Research Consortium: Member Institution of the MMRC. Hagerty: Mayo Clinic: Employment; Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Wolf: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Celgene: Speakers Bureau; Millennium: Speakers Bureau; Novartis: Speakers Bureau; Orthobiotech: Speakers Bureau. Davis: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Krishnan: Celgene: Speakers Bureau; Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Duarte: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Zimmerman: Millennium, Celgene: Speakers Bureau. Cisneros: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Kumar: Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding; Bayer: Research Funding; Multiple Myeloma Research Consortium: Member Institution of the MMRC; Merck: Consultancy, Research Funding; Millennium: Research Funding; Celgene: Consultancy, Research Funding. Birgin: Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Ott: Multiple Myeloma Research Consortium (MMRC): Employment. Tasca: Multiple Myeloma Research Consortium (MMRC): Employment. Kelley: Multiple Myeloma Research Consortium (MMRC): Employment. Anderson: Millennium: Consultancy; Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Celgene: Consultancy; Novartis: Consultancy; Onyx: Consultancy; Merck: Consultancy; Bristol-Myers Squibb: Consultancy; Acetylon: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees. Giusti: Multiple Myeloma Research Consortium (MMRC): Employment.

*signifies non-member of ASH