Study of Blood Samples From Newborns With Down Syndrome

NCT ID: NCT00959283

Last Updated: 2023-10-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

180 participants

Study Classification

OBSERVATIONAL

Study Start Date

2009-02-23

Study Completion Date

2023-09-30

Brief Summary

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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

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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.

Conditions

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Myeloid Proliferations Associated With Down Syndrome

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Ancillary-correlative

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.

Diagnostic Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Interventions

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Diagnostic Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pharmacological Study

Correlative studies

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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
Maximum Eligible Age

90 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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April D Sorrell

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

USA Health Strada Patient Care Center

Mobile, Alabama, United States

Site Status

Providence Alaska Medical Center

Anchorage, Alaska, United States

Site Status

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Kaiser Permanente Downey Medical Center

Downey, California, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

Mattel Children's Hospital UCLA

Los Angeles, California, United States

Site Status

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Valley Children's Hospital

Madera, California, United States

Site Status

Children's Hospital and Research Center at Oakland

Oakland, California, United States

Site Status

Kaiser Permanente-Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status

Sutter Medical Center Sacramento

Sacramento, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status

UCSF Medical Center-Mission Bay

San Francisco, California, United States

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Children's Hospital Colorado

Aurora, Colorado, United States

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Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

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Connecticut Children's Medical Center

Hartford, Connecticut, United States

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Yale University

New Haven, Connecticut, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

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MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Site Status

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Site Status

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

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Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

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Arnold Palmer Hospital for Children

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

UF Cancer Center at Orlando Health

Orlando, Florida, United States

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Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

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Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

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Tampa General Hospital

Tampa, Florida, United States

Site Status

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Site Status

Saint Mary's Hospital

West Palm Beach, Florida, United States

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Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

Memorial Health University Medical Center

Savannah, Georgia, United States

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University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Site Status

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, United States

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Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

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University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States

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Saint Jude Midwest Affiliate

Peoria, Illinois, United States

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Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

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Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, United States

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Blank Children's Hospital

Des Moines, Iowa, United States

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University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

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University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

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Norton Children's Hospital

Louisville, Kentucky, United States

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Tulane University Health Sciences Center

New Orleans, Louisiana, United States

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Children's Hospital New Orleans

New Orleans, Louisiana, United States

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Eastern Maine Medical Center

Bangor, Maine, United States

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Sinai Hospital of Baltimore

Baltimore, Maryland, United States

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Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

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Walter Reed National Military Medical Center

Bethesda, Maryland, United States

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Floating Hospital for Children at Tufts Medical Center

Boston, Massachusetts, United States

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Baystate Medical Center

Springfield, Massachusetts, United States

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C S Mott Children's Hospital

Ann Arbor, Michigan, United States

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Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

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Ascension Saint John Hospital

Detroit, Michigan, United States

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Michigan State University Clinical Center

East Lansing, Michigan, United States

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Hurley Medical Center

Flint, Michigan, United States

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Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

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Bronson Methodist Hospital

Kalamazoo, Michigan, United States

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Kalamazoo Center for Medical Studies

Kalamazoo, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

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Columbia Regional

Columbia, Missouri, United States

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Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

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Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

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Washington University School of Medicine

St Louis, Missouri, United States

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Mercy Hospital Saint Louis

St Louis, Missouri, United States

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Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

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University of Nebraska Medical Center

Omaha, Nebraska, United States

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University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Site Status

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, United States

Site Status

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States

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Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, United States

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Summerlin Hospital Medical Center

Las Vegas, Nevada, United States

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Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

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Hackensack University Medical Center

Hackensack, New Jersey, United States

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Saint Barnabas Medical Center

Livingston, New Jersey, United States

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Morristown Medical Center

Morristown, New Jersey, United States

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Saint Peter's University Hospital

New Brunswick, New Jersey, United States

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Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

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Newark Beth Israel Medical Center

Newark, New Jersey, United States

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Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States

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Overlook Hospital

Summit, New Jersey, United States

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University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

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Albany Medical Center

Albany, New York, United States

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Roswell Park Cancer Institute

Buffalo, New York, United States

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NYU Winthrop Hospital

Mineola, New York, United States

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The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

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Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

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Mount Sinai Hospital

New York, New York, United States

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NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

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University of Rochester

Rochester, New York, United States

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Stony Brook University Medical Center

Stony Brook, New York, United States

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State University of New York Upstate Medical University

Syracuse, New York, United States

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Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

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New York Medical College

Valhalla, New York, United States

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Mission Hospital Inc-Memorial Campus

Asheville, North Carolina, United States

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UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

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Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

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Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

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Duke University Medical Center

Durham, North Carolina, United States

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East Carolina University

Greenville, North Carolina, United States

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Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

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Sanford Broadway Medical Center

Fargo, North Dakota, United States

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Children's Hospital Medical Center of Akron

Akron, Ohio, United States

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Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

The Toledo Hospital/Toledo Children's Hospital

Toledo, Ohio, United States

Site Status

Mercy Children's Hospital

Toledo, Ohio, United States

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University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Natalie Warren Bryant Cancer Center at Saint Francis

Tulsa, Oklahoma, United States

Site Status

Legacy Emanuel Children's Hospital

Portland, Oregon, United States

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Legacy Emanuel Hospital and Health Center

Portland, Oregon, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

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Penn State Children's Hospital

Hershey, Pennsylvania, United States

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Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

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Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Prisma Health Richland Hospital

Columbia, South Carolina, United States

Site Status

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States

Site Status

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status

T C Thompson Children's Hospital

Chattanooga, Tennessee, United States

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East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Tech University Health Sciences Center-Amarillo

Amarillo, Texas, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

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Cook Children's Medical Center

Fort Worth, Texas, United States

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Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Site Status

Covenant Children's Hospital

Lubbock, Texas, United States

Site Status

Children's Hospital of San Antonio

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

University of Vermont and State Agricultural College

Burlington, Vermont, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

Naval Medical Center - Portsmouth

Portsmouth, Virginia, United States

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Carilion Clinic Children's Hospital

Roanoke, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Site Status

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, United States

Site Status

Madigan Army Medical Center

Tacoma, Washington, United States

Site Status

West Virginia University Charleston Division

Charleston, West Virginia, United States

Site Status

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Monash Medical Center-Clayton Campus

Clayton, Victoria, Australia

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

Janeway Child Health Centre

St. John's, Newfoundland and Labrador, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Site Status

Children's Hospital

London, Ontario, Canada

Site Status

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Québec, , Canada

Site Status

San Jorge Children's Hospital

San Juan, , Puerto Rico

Site Status

Countries

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United States Australia Canada Puerto Rico

Other Identifiers

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NCI-2011-02193

Identifier Type: REGISTRY

Identifier Source: secondary_id

COG-AAML08B1

Identifier Type: -

Identifier Source: secondary_id

CDR0000636115

Identifier Type: -

Identifier Source: secondary_id

AAML08B1

Identifier Type: -

Identifier Source: secondary_id

AAML08B1

Identifier Type: OTHER

Identifier Source: secondary_id

AAML08B1

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1CA189958

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAML08B1

Identifier Type: -

Identifier Source: org_study_id

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