Genetic Study of Children With Soft Tissue Sarcoma or Rhabdomyosarcoma

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00003793

Collaborator

National Cancer Institute (NCI) (NIH)

294

Enrollment

Locations

Duration (Months)

3.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes Sarcoma	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.

Study Design

Study Type:

Observational

Actual Enrollment :

294 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Clinical and Biological Predictors of Therapy-Related Leukemia

Study Start Date :

Dec 1, 1998

Actual Primary Completion Date :

Dec 1, 2005

Actual Study Completion Date :

Mar 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Event Free Survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Southern California Permanente Medical Group	Downey	California	United States	90242
2	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California	United States	90806
3	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
4	Children's Hospital Central California	Madera	California	United States	93638
5	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
6	Stanford Comprehensive Cancer Center at Stanford University Medical Center	Stanford	California	United States	94305
7	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut	United States	06360-2875
8	Alfred I. duPont Hospital for Children	Wilmington	Delaware	United States	19899
9	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
10	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
11	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida	United States	33901
12	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
13	Nemours Children's Clinic	Jacksonville	Florida	United States	32207-8482
14	Miami Children's Hospital	Miami	Florida	United States	33155
15	Baptist-South Miami Regional Cancer Program	Miami	Florida	United States	33176-2197
16	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida	United States	32803-1273
17	All Children's Hospital	St. Petersburg	Florida	United States	33701
18	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida	United States	33607
19	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
20	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
21	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
22	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
23	Blank Children's Hospital	Des Moines	Iowa	United States	50309
24	Kosair Children's Hospital	Louisville	Kentucky	United States	40232
25	Children's Hospital of New Orleans	New Orleans	Louisiana	United States	70118
26	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine	United States	04401
27	Maine Children's Cancer Program	Scarborough	Maine	United States	04074
28	C.S. Mott Children's Hospital at University of Michigan	Ann Arbor	Michigan	United States	48109-0286
29	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
30	Hurley Medical Center	Flint	Michigan	United States	48503
31	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan	United States	49503
32	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
33	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
34	Children's Hospitals and Clinics of Minneapolis	Minneapolis	Minnesota	United States	55404
35	University of Minnesota Medical Center & Children's Hospital - Fairview	Minneapolis	Minnesota	United States	55455
36	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
37	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
38	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
39	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
40	Siteman Cancer Center at Barnes-Jewish Hospital	St. Louis	Missouri	United States	63110
41	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey	United States	07601
42	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
43	Maimonides Cancer Center at Maimonides Medical Center	Brooklyn	New York	United States	11220
44	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
45	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
46	Mount Sinai Medical Center	New York	New York	United States	10029
47	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032
48	Stony Brook University Cancer Center	Stony Brook	New York	United States	11794-8174
49	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
50	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
51	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
52	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
53	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
54	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
55	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308-1062
56	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
57	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
58	Columbus Children's Hospital	Columbus	Ohio	United States	43205-2696
59	Children's Medical Center - Dayton	Dayton	Ohio	United States	45404-1815
60	Tod Children's Hospital - Forum Health	Youngstown	Ohio	United States	44501
61	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
62	Institute of Oncology at Vilnius University	Portland	Oregon	United States	97227
63	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
64	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134-1095
65	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
66	Greenville Hospital System Cancer Center	Greenville	South Carolina	United States	29605
67	East Tennessee Children's Hospital	Knoxville	Tennessee	United States	37901
68	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
69	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas	United States	79106
70	Medical City Dallas Hospital	Dallas	Texas	United States	75230
71	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
72	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
73	Covenant Children's Hospital	Lubbock	Texas	United States	79410
74	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900
75	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
76	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
77	INOVA Fairfax Hospital	Fairfax	Virginia	United States	22042-3300
78	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
79	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington	United States	99204
80	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia	United States	25302
81	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
82	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
83	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
84	Office of S. David Lang	Herston, Brisbane	Queensland	Australia	QLD 4029
85	Royal Children's Hospital	Parkville	Victoria	Australia	3052
86	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
87	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia	Canada	V6H 3V4
88	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
89	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
90	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
91	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 5P9
92	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
93	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
94	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5
95	Centre Hospitalier Universitaire de Quebec	Ste-Foy	Quebec	Canada	G1R 2J6
96	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan	Canada	S7N 4H4