Genetic Study of Children With Soft Tissue Sarcoma or Rhabdomyosarcoma

Children's Oncology Group

Status: Completed

Conditions: Sarcoma; Leukemia; Myelodysplastic Syndromes

Treatments: Genetic: clonality analysis; Genetic: mutation analysis; Genetic: microsatellite instability analysis

Study type: Observational

Funder types: NETWORK; NIH

Identifiers

NCT00003793

COG-AB9804 (Other Identifier)

AB9804

CDR0000066936 (Other Identifier)

CCG-B9804 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 294 patients

Sex: All

Ages: Under 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

294 participants in 2 patient groups

Identification of Genetical suceptibility prior to therapy

Description:

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.

Treatment:

Genetic: mutation analysis

Genetic: microsatellite instability analysis

Increased Risk Of T-MDS/AML before/after Therapy

Description:

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.

Treatment:

Genetic: mutation analysis

Genetic: microsatellite instability analysis

Genetic: clonality analysis