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Genetic Study of Children With Soft Tissue Sarcoma or Rhabdomyosarcoma

Completed
Conditions
Sarcoma
Leukemia
Myelodysplastic Syndromes
Interventions
Genetic: microsatellite instability analysis
Genetic: clonality analysis
Genetic: mutation analysis
Registration Number
NCT00003793
Lead Sponsor
Children's Oncology Group
Brief Summary

RATIONALE: Determination of genetic markers for soft tissue sarcoma or rhabdomyosarcoma may help doctors identify patients who are at risk for therapy-related leukemia.

PURPOSE: Clinical trial to study genetic testing of children with soft tissue sarcoma or rhabdomyosarcoma to identify children who are at risk of developing leukemia from the chemotherapy used to treat sarcoma.

Detailed Description

OBJECTIVES:

* Identify genetically susceptible patients to therapy-induced myelodysplastic syndrome or acute myelogenous leukemia (t-MDS/AML) prior to initiation of high-dose chemotherapy for sarcoma.

* Identify patients who are at increased risk of t-MDS/AML during or after therapy.

OUTLINE: Blood is collected from patients at diagnosis (preferably before chemotherapy or transfusion), at end of therapy, and at 6 months, 1 year, 2 years, and 3 years after therapy.

Blood specimens are examined by clonality analysis (HUMARA), variant cell frequency (glycophorin A assay), GST NAT2/CYP1A1 genotyping, microsatellite instability, and ras mutation detection (single strand conformation polymorphism and sequencing of mutant alleles).

Patients do not receive the results of the genetic testing and the results do not influence the type or duration of treatment.

PROJECTED ACCRUAL: A total of 321 patients will be accrued for this study within 4 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
294
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Identification of Genetical suceptibility prior to therapymicrosatellite instability analysisDetermine the glutathione-s-transferase theta (GSTT1) or glutathione-s-transferase mu (GSTM1) null genotype is more frequent in individuals with t-MDS/AML. Determine the GSTT1 or GSTM1 null genotype is associated with a reduced incidence of relapse of sarcoma. Determine NAT2 or CYP1A1 genotype influences risk of t-MDS/AML. Determine development of a "mutator phenotype" as demonstrated by developing microsatellite instability is an early marker of individuals likely to progress to t-MDS/AML.
Increased Risk Of T-MDS/AML before/after Therapyclonality analysisDetermine clonal hematopoiesis develops in children receiving high intensity alkylating agent chemotherapy for sarcomas. Determine development of clonal hematopoiesis is associated with increased frequency of t-MDS/AML. Determine measurement of somatic cell mutation frequency, measured by the glycophorin A (GPA) assay prior to and after chemotherapy will predict individuals at increased risk of t-MDS/AML. Identify individuals with ras gene mutations in normal peripheral blood cells after therapy, and whether the identification of such mutations is associated with increased risk of t-MDS/AML blood cells after therapy, and whether the identification of such mutations is associated with increased risk of t-MDS/AML.
Increased Risk Of T-MDS/AML before/after Therapymicrosatellite instability analysisDetermine clonal hematopoiesis develops in children receiving high intensity alkylating agent chemotherapy for sarcomas. Determine development of clonal hematopoiesis is associated with increased frequency of t-MDS/AML. Determine measurement of somatic cell mutation frequency, measured by the glycophorin A (GPA) assay prior to and after chemotherapy will predict individuals at increased risk of t-MDS/AML. Identify individuals with ras gene mutations in normal peripheral blood cells after therapy, and whether the identification of such mutations is associated with increased risk of t-MDS/AML blood cells after therapy, and whether the identification of such mutations is associated with increased risk of t-MDS/AML.
Identification of Genetical suceptibility prior to therapymutation analysisDetermine the glutathione-s-transferase theta (GSTT1) or glutathione-s-transferase mu (GSTM1) null genotype is more frequent in individuals with t-MDS/AML. Determine the GSTT1 or GSTM1 null genotype is associated with a reduced incidence of relapse of sarcoma. Determine NAT2 or CYP1A1 genotype influences risk of t-MDS/AML. Determine development of a "mutator phenotype" as demonstrated by developing microsatellite instability is an early marker of individuals likely to progress to t-MDS/AML.
Increased Risk Of T-MDS/AML before/after Therapymutation analysisDetermine clonal hematopoiesis develops in children receiving high intensity alkylating agent chemotherapy for sarcomas. Determine development of clonal hematopoiesis is associated with increased frequency of t-MDS/AML. Determine measurement of somatic cell mutation frequency, measured by the glycophorin A (GPA) assay prior to and after chemotherapy will predict individuals at increased risk of t-MDS/AML. Identify individuals with ras gene mutations in normal peripheral blood cells after therapy, and whether the identification of such mutations is associated with increased risk of t-MDS/AML blood cells after therapy, and whether the identification of such mutations is associated with increased risk of t-MDS/AML.
Primary Outcome Measures
NameTimeMethod
Event Free Survival
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (96)

All Children's Hospital

🇺🇸

St. Petersburg, Florida, United States

Tod Children's Hospital - Forum Health

🇺🇸

Youngstown, Ohio, United States

St. Christopher's Hospital for Children

🇺🇸

Philadelphia, Pennsylvania, United States

Cleveland Clinic Taussig Cancer Center

🇺🇸

Cleveland, Ohio, United States

Baptist-South Miami Regional Cancer Program

🇺🇸

Miami, Florida, United States

University of Texas Health Science Center at San Antonio

🇺🇸

San Antonio, Texas, United States

Methodist Children's Hospital of South Texas

🇺🇸

San Antonio, Texas, United States

UCSF Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

Vanderbilt-Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

🇺🇸

Washington, District of Columbia, United States

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

🇺🇸

Farmington, Connecticut, United States

NYU Cancer Institute at New York University Medical Center

🇺🇸

New York, New York, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Presbyterian Cancer Center at Presbyterian Hospital

🇺🇸

Charlotte, North Carolina, United States

Marshfield Clinic - Marshfield Center

🇺🇸

Marshfield, Wisconsin, United States

CCOP - Scott and White Hospital

🇺🇸

Temple, Texas, United States

Saskatoon Cancer Centre at the University of Saskatchewan

🇨🇦

Saskatoon, Saskatchewan, Canada

Children's Hospital Central California

🇺🇸

Madera, California, United States

Stanford Comprehensive Cancer Center at Stanford University Medical Center

🇺🇸

Stanford, California, United States

Jonsson Comprehensive Cancer Center at UCLA

🇺🇸

Los Angeles, California, United States

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

🇺🇸

Long Beach, California, United States

East Tennessee Children's Hospital

🇺🇸

Knoxville, Tennessee, United States

SUNY Upstate Medical University Hospital

🇺🇸

Syracuse, New York, United States

INOVA Fairfax Hospital

🇺🇸

Fairfax, Virginia, United States

Blank Children's Hospital

🇺🇸

Des Moines, Iowa, United States

Children's Medical Center - Dayton

🇺🇸

Dayton, Ohio, United States

Southern California Permanente Medical Group

🇺🇸

Downey, California, United States

Alfred I. duPont Hospital for Children

🇺🇸

Wilmington, Delaware, United States

Providence Cancer Center at Sacred Heart Medical Center

🇺🇸

Spokane, Washington, United States

Winship Cancer Institute of Emory University

🇺🇸

Atlanta, Georgia, United States

Nemours Children's Clinic

🇺🇸

Jacksonville, Florida, United States

Van Elslander Cancer Center at St. John Hospital and Medical Center

🇺🇸

Grosse Pointe Woods, Michigan, United States

Kaplan Cancer Center at St. Mary's Medical Center

🇺🇸

West Palm Beach, Florida, United States

Children's National Medical Center

🇺🇸

Washington, District of Columbia, United States

CancerCare of Maine at Eastern Maine Medial Center

🇺🇸

Bangor, Maine, United States

Lee Cancer Care of Lee Memorial Health System

🇺🇸

Fort Myers, Florida, United States

Hurley Medical Center

🇺🇸

Flint, Michigan, United States

Maine Children's Cancer Program

🇺🇸

Scarborough, Maine, United States

Children's Memorial Hospital - Chicago

🇺🇸

Chicago, Illinois, United States

Miami Children's Hospital

🇺🇸

Miami, Florida, United States

Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

🇺🇸

Savannah, Georgia, United States

Children's Hospitals and Clinics of Minneapolis

🇺🇸

Minneapolis, Minnesota, United States

University of Minnesota Medical Center & Children's Hospital - Fairview

🇺🇸

Minneapolis, Minnesota, United States

Spectrum Health Hospital - Butterworth Campus

🇺🇸

Grand Rapids, Michigan, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Siteman Cancer Center at Barnes-Jewish Hospital

🇺🇸

St. Louis, Missouri, United States

CCOP - Kalamazoo

🇺🇸

Kalamazoo, Michigan, United States

Maimonides Cancer Center at Maimonides Medical Center

🇺🇸

Brooklyn, New York, United States

Hackensack University Medical Center Cancer Center

🇺🇸

Hackensack, New Jersey, United States

University of Mississippi Medical Center

🇺🇸

Jackson, Mississippi, United States

Albert Einstein Cancer Center at Albert Einstein College of Medicine

🇺🇸

Bronx, New York, United States

Ellis Fischel Cancer Center at University of Missouri - Columbia

🇺🇸

Columbia, Missouri, United States

Mount Sinai Medical Center

🇺🇸

New York, New York, United States

Stony Brook University Cancer Center

🇺🇸

Stony Brook, New York, United States

Herbert Irving Comprehensive Cancer Center at Columbia University

🇺🇸

New York, New York, United States

Columbus Children's Hospital

🇺🇸

Columbus, Ohio, United States

Children's Hospital of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

Blumenthal Cancer Center at Carolinas Medical Center

🇺🇸

Charlotte, North Carolina, United States

Greenville Hospital System Cancer Center

🇺🇸

Greenville, South Carolina, United States

Covenant Children's Hospital

🇺🇸

Lubbock, Texas, United States

Edwards Comprehensive Cancer Center at Cabell Huntington Hospital

🇺🇸

Huntington, West Virginia, United States

Office of S. David Lang

🇦🇺

Herston, Brisbane, Queensland, Australia

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

Children's & Women's Hospital of British Columbia

🇨🇦

Vancouver, British Columbia, Canada

Cook Children's Medical Center - Fort Worth

🇺🇸

Fort Worth, Texas, United States

Children's Hospital Medical Center of Akron

🇺🇸

Akron, Ohio, United States

CCOP - MeritCare Hospital

🇺🇸

Fargo, North Dakota, United States

Royal Children's Hospital

🇦🇺

Parkville, Victoria, Australia

Princess Margaret Hospital for Children

🇦🇺

Perth, Western Australia, Australia

Medical City Dallas Hospital

🇺🇸

Dallas, Texas, United States

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

🇺🇸

Dallas, Texas, United States

Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

St. Vincent Hospital Regional Cancer Center

🇺🇸

Green Bay, Wisconsin, United States

IWK Health Centre

🇨🇦

Halifax, Nova Scotia, Canada

West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division

🇺🇸

Charleston, West Virginia, United States

Children's Hospital of The King's Daughters

🇺🇸

Norfolk, Virginia, United States

Texas Tech University Health Sciences Center School of Medicine - Amarillo

🇺🇸

Amarillo, Texas, United States

Centre Hospitalier Universitaire de Quebec

🇨🇦

Ste-Foy, Quebec, Canada

CancerCare Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

Hopital Sainte Justine

🇨🇦

Montreal, Quebec, Canada

Children's Hospital of Eastern Ontario

🇨🇦

Ottawa, Ontario, Canada

McMaster Children's Hospital at Hamilton Health Sciences

🇨🇦

Hamilton, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston General Hospital

🇨🇦

Kingston, Ontario, Canada

Barbara Ann Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Oklahoma University Medical Center

🇺🇸

Oklahoma City, Oklahoma, United States

Institute of Oncology at Vilnius University

🇺🇸

Portland, Oregon, United States

Mayo Clinic Cancer Center

🇺🇸

Rochester, Minnesota, United States

St. Joseph's Cancer Institute at St. Joseph's Hospital

🇺🇸

Tampa, Florida, United States

Florida Hospital Cancer Institute at Florida Hospital Orlando

🇺🇸

Orlando, Florida, United States

Kosair Children's Hospital

🇺🇸

Louisville, Kentucky, United States

C.S. Mott Children's Hospital at University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Wake Forest University Comprehensive Cancer Center

🇺🇸

Winston-Salem, North Carolina, United States

University of Florida Shands Cancer Center

🇺🇸

Gainesville, Florida, United States

Children's Hospital of New Orleans

🇺🇸

New Orleans, Louisiana, United States

Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

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