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Genetic Study of Children With Soft Tissue Sarcoma or Rhabdomyosarcoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00003793
First received: November 1, 1999
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
Leukemia
Myelodysplastic Syndromes
Sarcoma
Genetic: clonality analysis
Genetic: microsatellite instability analysis
Genetic: mutation analysis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Clinical and Biological Predictors of Therapy-Related Leukemia

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event Free Survival [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

blood


Enrollment: 294
Study Start Date: December 1998
Study Completion Date: March 2007
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Identification of Genetical suceptibility prior to therapy
Determine 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.
Genetic: microsatellite instability analysis Genetic: mutation analysis
Increased Risk Of T-MDS/AML before/after Therapy
Determine 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.
Genetic: clonality analysis Genetic: microsatellite instability analysis Genetic: mutation analysis

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.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Children receiving high dose chemotherapy for sarcomas.

Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of sarcoma including:

    • Rhabdomyosarcoma
    • Ewing's sarcoma
    • Primitive neuroectodermal tumor
    • Fibrosarcoma
    • Malignant peripheral nerve sheath tumor
    • Synovial cell sarcoma
    • Osteosarcoma
    • Other soft tissue sarcoma
  • Must be currently receiving intensive or high-dose chemotherapy for sarcoma

PATIENT CHARACTERISTICS:

Age:

  • Children

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Not specified

Renal:

  • Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003793

  Show 96 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Stella M. Davies, MBBS, PhD Children's Hospital Medical Center, Cincinnati
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00003793     History of Changes
Other Study ID Numbers: AB9804, COG-AB9804, CCG-B9804, CDR0000066936
Study First Received: November 1, 1999
Last Updated: August 4, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
secondary acute myeloid leukemia
secondary myelodysplastic syndromes
localized osteosarcoma
metastatic osteosarcoma
childhood soft tissue sarcoma
nonmetastatic childhood soft tissue sarcoma
metastatic childhood soft tissue sarcoma
childhood fibrosarcoma
childhood synovial sarcoma
childhood neurofibrosarcoma
previously untreated childhood rhabdomyosarcoma
localized Ewing sarcoma/peripheral primitive neuroectodermal tumor
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Rhabdomyosarcoma
Sarcoma
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Myosarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Muscle Tissue
Pathologic Processes
Precancerous Conditions

ClinicalTrials.gov processed this record on November 25, 2014