Study of Blood Samples From Newborns With Down Syndrome
- Conditions
- Myeloid Proliferations Associated With Down Syndrome
- Interventions
- Other: Diagnostic Laboratory Biomarker AnalysisOther: Pharmacological Study
- Registration Number
- NCT00959283
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
This research study is looking at blood samples from newborns with Down syndrome. Studying the genes expressed in samples of blood from patients with Down syndrome may help doctors identify biomarkers related to cancer.
- Detailed Description
PRIMARY OBJECTIVES:
I. To further our biological understanding of the natural history of transient myeloproliferative disorder (TMD) and its relationship to subsequent leukemia by facilitating the development of a TMD cell and protein bank, and repository of DNA/RNA from megakaryoblasts for future biological studies.
II. To investigate the biology of TMD molecular changes associated with resolution of TMD or its conversion to acute myeloid leukemia within each mortality-risk group by conducting GATA1 mutational analyses, hematopoiesis clonality studies, assessment of RAS mutations, and genomic instability studies using glycophorin A assays.
III. To determine if high-resolution microarray genomic analysis of TMD blasts (using Affymetrix SNP Genechip technology to assess gene expression, copy number variation, and loss of heterozygosity) can predict the development of subsequent leukemia.
IV. To determine the relationship of minimal residual disease (monitored by peripheral blood flow cytometry and GATA1 mutational studies) to clinical remission status and development of subsequent leukemia within each mortality-risk group of TMD patients.
V. To evaluate the relationship between karyotype (including FISH analysis) and subsequent leukemia in TMD patients.
VI. To examine pharmacogenetics and in vitro drug sensitivity to cytarabine (MTT assay) in blasts from TMD patients.
VII. To examine the relationship of functional polymorphisms in Phase I and Phase II drug detoxification genes, DNA repair, and DNA synthesis pathways that may modify susceptibility to leukemia and outcome in TMD patients.
VIII. To determine the relationship between fibrosis-associated serum factors (e.g., platelet-derived growth factor, transforming growth factor beta, N-terminal peptide of III procollagen, type IV collagen, and hyaluronic acid) and event-free survival.
OUTLINE: This is a multicenter study.
Patients undergo peripheral blood collection periodically for biomarker analysis. Samples are analyzed for GATA1 mutations by real-time PCR, polymorphisms, cytogenetics, and K-RAS mutations, gene expression, drug sensitivity patterns, and minimal residual disease by flow cytometry.
Patients are followed up periodically for 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 180
-
Diagnosis of transient myeloproliferative disorder (TMD) at < 90 days of age and meeting 1 of the following criteria:
-
A diagnosis of Down syndrome or Down syndrome mosaicism AND non-erythroid and non-lymphoid blasts (any amount) in the peripheral blood verified with a second sample
- Patients with typical physical characteristics of Down syndrome are allowed before cytogenetic or FISH confirmation of the diagnosis
-
Trisomy 21-positive leukemic blasts documented by biopsy of any organ (including > 5% non-erythroid/non-lymphoid blasts documented by bone marrow aspirate or biopsy)
- Infants with isolated trisomy 21 positivity identified only in the leukemic blasts are allowed
-
-
Institutional immunophenotype characterization is required for study enrollment
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Ancillary-correlative Diagnostic Laboratory Biomarker Analysis Patients undergo peripheral blood collection periodically for biomarker analysis. Samples are analyzed for GATA1 mutations by real-time PCR, polymorphisms, cytogenetics, and K-RAS mutations, gene expression, drug sensitivity patterns, and minimal residual disease by flow cytometry. Ancillary-correlative Pharmacological Study Patients undergo peripheral blood collection periodically for biomarker analysis. Samples are analyzed for GATA1 mutations by real-time PCR, polymorphisms, cytogenetics, and K-RAS mutations, gene expression, drug sensitivity patterns, and minimal residual disease by flow cytometry.
- Primary Outcome Measures
Name Time Method Event-free survival Up to 5 years
- Secondary Outcome Measures
Name Time Method Overall survival Up to 5 years Incidence of TMD-related mortality Up to 5 years Incidence of subsequent leukemia for patients with resolved TMD Up to 5 years
Trial Locations
- Locations (189)
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
UCLA / Jonsson Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Nevada Cancer Research Foundation CCOP
🇺🇸Las Vegas, Nevada, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Children's Hospital of San Antonio
🇺🇸San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
UCSF Medical Center-Parnassus
🇺🇸San Francisco, California, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Children's Hospital and Research Center at Oakland
🇺🇸Oakland, California, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Mattel Children's Hospital UCLA
🇺🇸Los Angeles, California, United States
Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Michigan State University Clinical Center
🇺🇸East Lansing, Michigan, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Natalie Warren Bryant Cancer Center at Saint Francis
🇺🇸Tulsa, Oklahoma, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸Oak Lawn, Illinois, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Mercy Children's Hospital
🇺🇸Toledo, Ohio, United States
Naval Medical Center - Portsmouth
🇺🇸Portsmouth, Virginia, United States
Saint Vincent Hospital and Health Care Center
🇺🇸Indianapolis, Indiana, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
The Toledo Hospital/Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
NYU Winthrop Hospital
🇺🇸Mineola, New York, United States
Cardinal Glennon Children's Medical Center
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Janeway Child Health Centre
🇨🇦Saint John's, Newfoundland and Labrador, Canada
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Columbia Regional
🇺🇸Columbia, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Mission Hospital Inc-Memorial Campus
🇺🇸Asheville, North Carolina, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸Tacoma, Washington, United States
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦Montreal, Quebec, Canada
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸Green Bay, Wisconsin, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Texas Tech University Health Sciences Center-Amarillo
🇺🇸Amarillo, Texas, United States
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
Children's Hospital
🇨🇦London, Ontario, Canada
University of Vermont and State Agricultural College
🇺🇸Burlington, Vermont, United States
T C Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Monash Medical Center-Clayton Campus
🇦🇺Clayton, Victoria, Australia
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Kingston Health Sciences Centre
🇨🇦Kingston, Ontario, Canada
West Virginia University Charleston Division
🇺🇸Charleston, West Virginia, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
San Jorge Children's Hospital
🇵🇷San Juan, Puerto Rico
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Carilion Clinic Children's Hospital
🇺🇸Roanoke, Virginia, United States
The Montreal Children's Hospital of the MUHC
🇨🇦Montreal, Quebec, Canada
Ascension Saint John Hospital
🇺🇸Detroit, Michigan, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
Legacy Emanuel Children's Hospital
🇺🇸Portland, Oregon, United States
Legacy Emanuel Hospital and Health Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Saint Luke's Mountain States Tumor Institute
🇺🇸Boise, Idaho, United States
Floating Hospital for Children at Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Arnold Palmer Hospital for Children
🇺🇸Orlando, Florida, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
UF Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
USA Health Strada Patient Care Center
🇺🇸Mobile, Alabama, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Prisma Health Richland Hospital
🇺🇸Columbia, South Carolina, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Kalamazoo Center for Medical Studies
🇺🇸Kalamazoo, Michigan, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States