Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00005596

Collaborator

National Cancer Institute (NCI) (NIH)

1,076

Enrollment

123

Locations

Arms

Duration (Months)

8.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which regimen of chemotherapy is more effective for acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is comparing four regimens of combination chemotherapy to see how well they work in treating children with newly diagnosed acute lymphoblastic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: pegaspargase Drug: thioguanine Drug: vincristine sulfate	Phase 3

Detailed Description

OBJECTIVES:

Determine if multidrug delayed-intensification therapy improves outcome in children with newly diagnosed standard-risk acute lymphocytic leukemia.
Compare the efficacy and toxicity of methotrexate administered over 4 hours vs methotrexate administered over 24 hours in this patient population.
Determine the correlation between event-free survival, minimal residual disease, and early response in this patient population treated with this multiple drug regimen.

OUTLINE: This is a randomized, multicenter study.

Induction (weeks 1-4): Patients receive induction therapy on POG 9900.
Consolidation (weeks 5-32): Patients are randomized to one of four treatment arms. Patients with t(1;19) are randomized to either arm III or arm IV.
Arm I (weeks 5-24): Patients receive IT methotrexate (MTX) on day 1 followed by MTX IV over 20 minutes followed by MTX continuously over 23.6 hours on weeks 7, 10, 13, 16,19, and 22. At 42 hours after the beginning of the MTX infusion, patients receive oral leucovorin calcium every 6 hours for a total of 3 doses. Patients also receive oral mercaptopurine daily beginning on week 5 and continuing until the completion of consolidation therapy; oral dexamethasone twice daily on days 1-7 of weeks 8 and 17; and vincristine IV on day 1 of weeks 8, 9, 17, and 18.
Arm II (weeks 5-24): Patients receive MTX IV over 4 hours on weeks 7, 10, 13, 16, 19, and 22. At 42 hours after the beginning of the MTX infusion, patients receive oral leucovorin calcium as in arm I. Patients also receive mercaptopurine, dexamethasone, vincristine, and IT MTX as in arm I.
Arm III (weeks 5-32): Patients receive MTX IV as in arm I on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; pegaspargase IM on day 2, 3, OR 4 of week 16; and oral mercaptopurine daily on weeks 5-13, and from week 24 until the completion of consolidation therapy. Patients also receive IT MTX as in arm I on weeks 7, 10, 13, 16, 20, 21, and 30; oral dexamethasone twice daily on weeks 8, 16-18, and 28 for a total of 35 days; vincristine IV on day 1 of weeks 8, 9, 16, 17, 18, 28, and 29; daunorubicin IV on day 1 of weeks 16-18; cyclophosphamide IV over 30 minutes on day 1 of week 20; cytarabine IV or subcutaneously daily on days 2-5 of weeks 20 and 21; and oral thioguanine daily on weeks 20-21.
Arm IV (weeks 5-32): Patients receive MTX IV as in arm II on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; and pegaspargase, mercaptopurine, IT MTX, dexamethasone, vincristine, daunorubicin, cyclophosphamide, cytarabine, and thioguanine as in arm III.
Intensive continuation (weeks 25-80): At weeks 25-72 for arms I and II, and at weeks 33-80 for arms III and IV, patients receive oral MTX every 6 hours for 4 doses on weeks 1, 3, 5, 7, 9, and 11; oral mercaptopurine daily; oral leucovorin calcium every 12 hours for 2 doses beginning 48 hours after the start of MTX; IT MTX and vincristine IV on day 1 of week 12; and oral dexamethasone twice daily on days 1-7, beginning with the administration of vincristine. Treatment repeats every 12 weeks for 4 courses.
Additional continuation (weeks 73-130): At weeks 73-130 for arms I and II, and at weeks 81-130 for arms III and IV, patients receive oral MTX weekly; oral mercaptopurine daily; vincristine IV on day 1 every 12 weeks; oral dexamethasone as during intensive continuation therapy; and IT MTX on day 1 every 12 weeks, beginning with the last week of the first course (in place of oral MTX).

Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then every 6-12 months for 1 year.

PROJECTED ACCRUAL: A total of 1,014 patients will be accrued for this study within 3.22 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

1076 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

ALinC 17: Protocol for Patients With Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL): A Phase III Study

Study Start Date :

Apr 1, 2000

Actual Primary Completion Date :

Jul 1, 2005

Actual Study Completion Date :

Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive IT methotrexate on day 1 followed by methotrexate IV over 20 minutes followed by methotrexate continuously over 23.6 hrs on wks 7, 10, 13, 16,19, and 22. At 42 hrs after the beginning of the methotrexate infusion, patients receive oral leucovorin calcium every 6 hrs for a total of 3 doses. Patients also receive oral mercaptopurine daily beginning on wk 5 and continuing until the completion of consolidation therapy; oral dexamethasone twice daily on days 1-7 of wks 8 and 17; and vincristine sulfate IV on day 1 of wks 8, 9, 17, and 18.	Drug: dexamethasone 6 mg/m2/day divided BID for 7 days during weeks 8 and 17. Other Names: DEX Drug: leucovorin calcium 5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX. Drug: mercaptopurine 50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL Other Names: 6-MP Drug: methotrexate IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22. IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22. Other Names: MTX Drug: vincristine sulfate 1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg) Other Names: VCR
Experimental: Arm II Patients receive methotrexate IV over 4 hours on weeks 7, 10, 13, 16, 19, and 22. At 42 hours after the beginning of the methotrexate infusion, patients receive oral leucovorin calcium as in arm I. Patients also receive mercaptopurine, dexamethasone, vincristine sulfate, and IT methotrexate as in arm I.	Drug: dexamethasone 6 mg/m2/day divided BID for 7 days during weeks 8 and 17. Other Names: DEX Drug: leucovorin calcium 5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX. Drug: mercaptopurine 50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL Other Names: 6-MP Drug: methotrexate IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22. IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22. Other Names: MTX Drug: vincristine sulfate 1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg) Other Names: VCR
Experimental: Arm III Patients receive methotrexate IV as in arm I on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; pegaspargase IM on day 2, 3, OR 4 of wk 16; oral mercaptopurine daily on wks 5-13, and from wk 24 until the completion of consolidation therapy. Patients also receive IT methotrexate as in arm I on wks 7, 10, 13, 16, 20, 21, and 30; oral dexamethasone 2x daily on weeks 8, 16-18, and 28 for a total of 35 days; vincristine sulfate IV on day 1 of wks 8, 9, 16, 17, 18, 28, and 29; daunorubicin hydrochloride IV on day 1 of wks 16-18; cyclophosphamide IV over 30 minutes on day 1 of week 20; cytarabine IV or subcutaneously daily on days 2-5 of wks 20 and 21; and oral thioguanine daily on wks 20-21.	Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride 30 mg/m2 IV Day 1 of weeks 16, 17, and 18. Give Week 16 dose if ANC ≥ 500/μL and platelets ≥ 75,000/μL. Continue to give during Weeks 17 and 18, even in the face of uncomplicated myelosuppression Other Names: daunomycin Drug: dexamethasone 6 mg/m2/day divided BID for 7 days during weeks 8 and 17. Other Names: DEX Drug: leucovorin calcium 5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX. Drug: mercaptopurine 50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL Other Names: 6-MP Drug: methotrexate IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22. IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22. Other Names: MTX Drug: pegaspargase 2,500 IU/m2 will be given IM x 1 on Days 2,3,or 4 of Week 16; > or = 1 day after the IT MTX Other Names: PEG Drug: thioguanine 60 mg/m2 po qhs during Weeks 20 and 21 (total 14 days). Start week 20 when ANC > or = 500/ul and platelets > or = 75,000/uL. Continue to give all 14 doses despite uncomplicated myelosuppression. Other Names: 6-TG Drug: vincristine sulfate 1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg) Other Names: VCR
Experimental: Arm IV Patients receive methotrexate IV as in arm II on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; and pegaspargase, mercaptopurine, IT methotrexate, dexamethasone, vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, cytarabine, and thioguanine as in arm III.	Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride 30 mg/m2 IV Day 1 of weeks 16, 17, and 18. Give Week 16 dose if ANC ≥ 500/μL and platelets ≥ 75,000/μL. Continue to give during Weeks 17 and 18, even in the face of uncomplicated myelosuppression Other Names: daunomycin Drug: dexamethasone 6 mg/m2/day divided BID for 7 days during weeks 8 and 17. Other Names: DEX Drug: leucovorin calcium 5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX. Drug: mercaptopurine 50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL Other Names: 6-MP Drug: methotrexate IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22. IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22. Other Names: MTX Drug: pegaspargase 2,500 IU/m2 will be given IM x 1 on Days 2,3,or 4 of Week 16; > or = 1 day after the IT MTX Other Names: PEG Drug: thioguanine 60 mg/m2 po qhs during Weeks 20 and 21 (total 14 days). Start week 20 when ANC > or = 500/ul and platelets > or = 75,000/uL. Continue to give all 14 doses despite uncomplicated myelosuppression. Other Names: 6-TG Drug: vincristine sulfate 1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg) Other Names: VCR

Outcome Measures

Primary Outcome Measures

Improvement in outcome in children receiving multidrug delayed-intensification therapy [Up to 4 years]
The overall plan is to accrue for 3.1 years or until all accrual goals have been met, whichever occurs first. Since power is determined by event-rates, lower or higher than expected event rates could lead to an amendment to alter the accrual goal. This consideration will be made independent of arm-specific outcome, in order to eliminate bias

Secondary Outcome Measures

Event-free survival, minimal residual disease, and early response [5 years]
The test statistic will compare Kaplan-Meier curves. Cox multiple regression will be utilized.
Occurrence of anticipated failures [Up to 5 years]
An O'Brien-Fleming analysis will be conducted.
Total grade 3+ central nervous system (CNS) toxicity rates based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [Up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Confirmed diagnosis of newly diagnosed B-precursor acute lymphocytic leukemia
Standard risk (not low, high, or very high risk)
Prior registration and treatment on POG 9900 Classification Study

PATIENT CHARACTERISTICS:

Age:

1 to 21 at diagnosis

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

Other:

Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of South Alabama Cancer Research Institute	Mobile	Alabama	United States	36604
3	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724
4	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
5	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
6	Stanford Cancer Center at Stanford University Medical Center	Palo Alto	California	United States	94304-1812
7	Sutter Cancer Center	Sacramento	California	United States	95816
8	University of California Davis Cancer Center	Sacramento	California	United States	95817
9	Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego	San Diego	California	United States	92120
10	Children's Hospital and Health Center, San Diego	San Diego	California	United States	92123-4282
11	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051-5386
12	Yale Comprehensive Cancer Center	New Haven	Connecticut	United States	06520-8064
13	Broward General Medical Center	Fort Lauderdale	Florida	United States	33316
14	Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
15	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0296
16	Joe DiMaggio Children's Hospital at Memorial	Hollywood	Florida	United States	33021
17	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
18	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida	United States	30101
19	Miami Children's Hospital	Miami	Florida	United States	33155
20	Baptist-South Miami Regional Cancer Program	Miami	Florida	United States	33176-2197
21	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
22	Nemours Children's Clinic-Orlando	Orlando	Florida	United States	32806
23	Sacred Heart Children's Hospital	Pensacola	Florida	United States	32504
24	All Children's Hospital	St. Petersburg	Florida	United States	33701
25	St. Joseph's Children's Hospital	Tampa	Florida	United States	33677-4227
26	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
27	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus	Atlanta	Georgia	United States	30342
28	MBCCOP-Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912-4000
29	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
30	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859-5000
31	Rush University Medical Center	Chicago	Illinois	United States	60612
32	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
33	Advocate Hope Children's Hospital	Oak Lawn	Illinois	United States	60453
34	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
35	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
36	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
37	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
38	Wesley Medical Center	Wichita	Kansas	United States	67214
39	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
40	Tulane Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana	United States	70112
41	Children's Hospital of New Orleans	New Orleans	Louisiana	United States	70118
42	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
43	Pediatric Specialty Clinic at Eastern Maine Medical Center	Bangor	Maine	United States	04401
44	Maine Children's Cancer Program	Scarborough	Maine	United States	04074-9308
45	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201-1595
46	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
47	Walter Reed Army Medical Center	Silver Spring	Maryland	United States	20910
48	Floating Hospital for Children	Boston	Massachusetts	United States	02111
49	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114-2696
50	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
51	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts	United States	01655
52	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
53	Van Elslander Cancer Center at St. John Hospital and Medical Center	Detroit	Michigan	United States	48236
54	Hurley Medical Center	Flint	Michigan	United States	48503
55	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
56	Keesler Medical Center - Keesler Air Force Base	Keesler AFB	Mississippi	United States	39534-2511
57	University of Missouri - Columbia	Columbia	Missouri	United States	65203
58	Cardinal Glennon Children's Hospital	Saint Louis	Missouri	United States	63104
59	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
60	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
61	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
62	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico	United States	87131
63	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
64	Schneider Children's Hospital	New Hyde Park	New York	United States	11042
65	Mount Sinai Medical Center	New York	New York	United States	10029
66	Beth Israel Medical Center - Singer Division	New York	New York	United States	10128
67	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
68	Long Island Cancer Center at Stony Brook University Hospital	Stony Brook	New York	United States	11794
69	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
70	Mission Hospitals - Memorial Campus	Asheville	North Carolina	United States	28801
71	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
72	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233
73	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
74	Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital	Greenville	North Carolina	United States	27858-4354
75	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1081
76	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
77	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
78	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
79	Legacy Emanuel Hospital and Health Center & Children's Hospital	Portland	Oregon	United States	97227
80	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134-1095
81	Rhode Island Hospital	Providence	Rhode Island	United States	02903
82	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
83	Children's Hospital of Greenville Hospital System	Greenville	South Carolina	United States	29605
84	East Tennessee State University Cancer Center at Johnson City Medical Center	Johnson City	Tennessee	United States	37614-0622
85	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
86	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78466
87	Medical City Dallas Hospital	Dallas	Texas	United States	75230
88	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390-9063
89	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
90	University of Texas Medical Branch	Galveston	Texas	United States	77555-0209
91	Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Houston	Texas	United States	77030-2399
92	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas	United States	78236
93	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78207
94	MBCCOP - South Texas Pediatrics	San Antonio	Texas	United States	78229-3900
95	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
96	Center for Cancer Prevention and Care at Scott and White Clinic	Temple	Texas	United States	76508
97	Vermont Cancer Center at University of Vermont	Burlington	Vermont	United States	05401-3498
98	Cancer Center at the University of Virginia	Charlottesville	Virginia	United States	22908
99	INOVA Fairfax Hospital	Falls Church	Virginia	United States	22042-3300
100	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-5100
101	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia	United States	23298-0212
102	Carilion Medical Center for Children at Roanoke Community Hospital	Roanoke	Virginia	United States	24029
103	Madigan Army Medical Center	Tacoma	Washington	United States	98431-0001
104	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia	United States	25302
105	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia	United States	26506-9300
106	St. Vincent Hospital	Green Bay	Wisconsin	United States	54307-9070
107	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449
108	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
109	Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
110	Royal Children's Hospital	Brisbane	Queensland	Australia	4029
111	Royal Children's Hospital	Parkville	Victoria	Australia	3052
112	Alberta Children's Hospital	Calgary	Alberta	Canada	T2T 5C7
113	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
114	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8S 4J9
115	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
116	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
117	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec	Canada	H3G 1A4
118	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5
119	Centre de Recherche du Centre Hospitalier de l'Universite Laval	Sainte Foy	Quebec	Canada	GIV 4G2
120	University Medical Center Groningen	Groningen		Netherlands	9700 RB
121	San Jorge Children's Hospital	Santurce		Puerto Rico	00912
122	Swiss Pediatric Oncology Group Bern	Bern		Switzerland	CH 3010
123	Swiss Pediatric Oncology Group Geneva	Geneva		Switzerland	CH 1211