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Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
Study Purpose
This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work in treating young patients with newly diagnosed supratentorial primitive neuroectodermal tumors or high-risk medulloblastoma when given before additional intense chemotherapy followed by peripheral blood stem cell rescue. It is not yet known which combination chemotherapy regimen is more effective when given before a peripheral stem cell transplant in treating supratentorial primitive neuroectodermal tumors or medulloblastoma.
Recruitment Criteria
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Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
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Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
| Eligible Ages | N/A - 2 Years |
| Gender | All |
Inclusion Criteria:
- - High-risk medulloblastoma defined by any of the following: - > 1.5 cm^2 residual disease for any medulloblastoma histology, or.
- - Lumbar cerebral spinal fluid (CSF) cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery unless contraindicated, or.
- - Magnetic resonance imaging (MRI) evidence of M2 or M3 metastatic disease, or.
- - M4 disease.
- - Supratentorial primitive neuroectodermal tumor (PNET) (any M-stage) will be eligible for study entry.
- - Children less than 8 months of age at the time of definitive surgery with or without measurable radiographic residual tumor with M0 stage medulloblastoma will be eligible for study entry.
- - Patients with anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor.
- - Patients with M0 classic, non-desmoplastic medulloblastoma (R1) with radiographically measurable residual disease < 1.5 cm^2 are eligible.
- - Cranial MRI (with and without gadolinium) must be done pre-operatively; post-operatively, cranial MRI (with and without gadolinium) must be done, preferably within 48 hours of surgery; entire spinal MRI must be obtained either pre-operatively (with gadolinium) or post-operatively (at least 10 days following surgery) prior to study enrollment (with and without gadolinium); patients with MRI evidence of spinal disease are eligible for this study.
- - Evaluation of lumbar CSF cytology (cytospin preparation for microscopic evaluation) must be performed either pre-operatively or at least 10 days after definitive surgery unless contraindicated.
- - Patient must have a life expectancy > 8 weeks.
- - Patient must have received no prior radiation therapy or chemotherapy other than corticosteroids; corticosteroids are allowable for all patients.
- - Creatinine clearance or radioisotope glomerular filtration rate >= 60 mL/min.
- - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and.
- - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT) (alanine transaminase [ALT]) < 2 x ULN for age.
- - Shortening fraction >= 27% by echocardiogram, or.
- - Ejection fraction >= 47% by radionuclide angiogram.
- - No evidence of dyspnea at rest.
- - Pulse oximetry > 94% on room air.
- - Peripheral absolute neutrophil count (ANC) > 1,000/uL.
- - Platelet count > 100,000/uL (transfusion independent) - Hemoglobin greater than 8 g/dL (may have received red blood cell [RBC] transfusions allowed) - Hold trimethoprim/sulfamethoxazole (Bactrim) on the day of high-dose methotrexate (HDMTX) infusion and continue to hold until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) - Avoid probenecid, penicillins, cephalosporins, aspirin, proton pump inhibitors and nonsteroidal anti-inflammatory drug (NSAIDS) on the day of methotrexate and continue until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) as renal excretion of methotrexate is inhibited by these agents.
- - Avoid IV contrast media, urinary acidifiers, phenytoin, and fosphenytoin on the day of methotrexate and until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) - Concurrent use of enzyme inducing anticonvulsants (e.g. phenytoin, phenobarbital, and carbamazepine) should be avoided.
- - Clinically significant drug interactions have been reported when using vincristine with strong cytochrome P450 (CYP450) family 3 subfamily A member 4 (3A4) inhibitors and inducers; selected strong inhibitors of cytochrome P450 3A4 include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort; the use of these drugs should be avoided with vincristine.
- - All patients and/or their parents or legal guardians must sign a written informed consent.
Trial Details
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Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT00336024 |
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Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 3 |
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Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Children's Oncology Group |
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Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Claire M Mazewski |
| Principal Investigator Affiliation | Children's Oncology Group |
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Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Other, NIH |
| Overall Status | Active, not recruiting |
| Countries | Australia, Canada, Puerto Rico, United States |
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Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Anaplastic Medulloblastoma, Medulloblastoma, Supratentorial Embryonal Tumor, Not Otherwise Specified, Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor |
PRIMARY OBJECTIVES:
- I. To determine if treatment of infants with high risk primitive neuroectodermal tumors (PNET) central nervous system (CNS) tumors with intensive chemotherapy plus high-dose methotrexate and peripheral blood stem cell rescue results in a higher complete response rate then the same regimen without methotrexate.
- I. To determine whether biologic characterization of these tumors will refine therapeutic stratification separating atypical teratoid rhabdoid tumors (AT/RT) from primitive neuroectodermal tumors (PNETs) and possibly identifying other markers of value for stratification within the group of PNETs.
- II. To determine if event free survival (EFS) and patterns of failure differ between the methotrexate arm versus the arm without methotrexate.
- III. To compare the acute, chronic and late effects of these two very intensive regimens, especially as to the tolerance of the same consolidation regimen following the differing induction regimens.
- IV. To compare the gastrointestinal and nutritional toxicities of these intense regimens.
- V. To describe and compare the quality of life outcomes and neuropsychological effects of these intense systemic therapies.
Arms
Active Comparator: Arm I (induction+consolidation chemotherapy, autologous PBSC)
Patients receive vincristine IV over 1 minute on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 5 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Experimental: Arm II (induction+consolidation chemotherapy, autologous PBSC)
Patients receive vincristine IV over 1 minute on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or PO every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 5 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Procedure: - Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC resuce
Drug: - Carboplatin
Given IV
Drug: - Cisplatin
Given IV
Drug: - Cyclophosphamide
Given IV
Drug: - Etoposide
Given IV
Biological: - Filgrastim
Given IV or SC
Other: - Laboratory Biomarker Analysis
Correlative studies
Drug: - Leucovorin Calcium
Given IV or orally
Drug: - Methotrexate
Given IV
Other: - Quality-of-Life Assessment
Ancillary studies
Drug: - Thiotepa
Given IV
Drug: - Vincristine Sulfate
Given IV
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
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Children's Hospital of Alabama
Birmingham, Alabama, 35233
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University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
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Phoenix Childrens Hospital
Phoenix, Arizona, 85016
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Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
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University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
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Kaiser Permanente Downey Medical Center
Downey, California, 90242
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Loma Linda University Medical Center
Loma Linda, California, 92354
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Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
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Children's Hospital Los Angeles
Los Angeles, California, 90027
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Cedars Sinai Medical Center
Los Angeles, California, 90048
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Valley Children's Hospital
Madera, California, 93636
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Children's Hospital of Orange County
Orange, California, 92868
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Sutter Medical Center Sacramento
Sacramento, California, 95816
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University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
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Rady Children's Hospital - San Diego
San Diego, California, 92123
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UCSF Medical Center-Parnassus
San Francisco, California, 94143
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Children's Hospital Colorado
Aurora, Colorado, 80045
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Connecticut Children's Medical Center
Hartford, Connecticut, 06106
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Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
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Children's National Medical Center
Washington, District of Columbia, 20010
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Address
Broward Health Medical Center
Fort Lauderdale, Florida, 33316
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Lee Memorial Health System
Fort Myers, Florida, 33901
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Address
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
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Address
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610
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Address
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Status
Address
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Status
Address
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
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Address
Nicklaus Children's Hospital
Miami, Florida, 33155
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Address
AdventHealth Orlando
Orlando, Florida, 32803
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Address
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Status
Address
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806
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Address
Orlando Health Cancer Institute
Orlando, Florida, 32806
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Address
Nemours Children's Hospital
Orlando, Florida, 32827
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Address
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
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Address
Johns Hopkins All Children's Hospital
Saint Petersburg, Florida, 33701
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Address
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
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Address
Saint Mary's Hospital
West Palm Beach, Florida, 33407
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Address
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
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Address
Memorial Health University Medical Center
Savannah, Georgia, 31404
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Address
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
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Address
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
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Address
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
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Address
Loyola University Medical Center
Maywood, Illinois, 60153
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Address
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453
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Address
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260
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Address
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
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Address
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
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Norton Children's Hospital
Louisville, Kentucky, 40202
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Address
Tulane University School of Medicine
New Orleans, Louisiana, 70112
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Address
Eastern Maine Medical Center
Bangor, Maine, 04401
Status
Address
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
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Address
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
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Address
Tufts Children's Hospital
Boston, Massachusetts, 02111
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Address
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Status
Address
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
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Address
Michigan State University Clinical Center
East Lansing, Michigan, 48824
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Address
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
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Address
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
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Address
Kalamazoo Center for Medical Studies
Kalamazoo, Michigan, 49008
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Address
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
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Address
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
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Address
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
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Address
University of Mississippi Medical Center
Jackson, Mississippi, 39216
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Address
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
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Address
Cardinal Glennon Children's Medical Center
Saint Louis, Missouri, 63104
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Address
Washington University School of Medicine
Saint Louis, Missouri, 63110
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Address
Mercy Hospital Saint Louis
Saint Louis, Missouri, 63141
Status
Address
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
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Address
Nevada Cancer Research Foundation NCORP
Las Vegas, Nevada, 89169
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Address
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Status
Address
Morristown Medical Center
Morristown, New Jersey, 07960
Status
Address
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Status
Address
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
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Address
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
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Address
Overlook Hospital
Summit, New Jersey, 07902
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Address
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
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Address
Montefiore Medical Center - Moses Campus
Bronx, New York, 10467
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Address
Roswell Park Cancer Institute
Buffalo, New York, 14263
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Address
NYU Langone Hospital - Long Island
Mineola, New York, 11501
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Address
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
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Address
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
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Address
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
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Address
University of Rochester
Rochester, New York, 14642
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Address
Stony Brook University Medical Center
Stony Brook, New York, 11794
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Address
New York Medical College
Valhalla, New York, 10595
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Address
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
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Address
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
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Address
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
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Address
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
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Address
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
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Address
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
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Address
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
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Address
Nationwide Children's Hospital
Columbus, Ohio, 43205
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Address
Dayton Children's Hospital
Dayton, Ohio, 45404
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Address
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
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Address
Mercy Children's Hospital
Toledo, Ohio, 43608
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Address
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
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Address
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
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Address
Legacy Emanuel Hospital and Health Center
Portland, Oregon, 97227
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Address
Oregon Health and Science University
Portland, Oregon, 97239
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Address
Geisinger Medical Center
Danville, Pennsylvania, 17822
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Address
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
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Address
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
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Address
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
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Address
Medical University of South Carolina
Charleston, South Carolina, 29425
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Address
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
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Address
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
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Address
Greenville Cancer Treatment Center
Greenville, South Carolina, 29605
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Address
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
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East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
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Address
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Status
Address
Texas Tech University Health Sciences Center-Amarillo
Amarillo, Texas, 79106
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Address
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
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Address
Medical City Dallas Hospital
Dallas, Texas, 75230
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Address
Cook Children's Medical Center
Fort Worth, Texas, 76104
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Address
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
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Address
Covenant Children's Hospital
Lubbock, Texas, 79410
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Address
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
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Address
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
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Address
Primary Children's Hospital
Salt Lake City, Utah, 84113
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Address
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
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Address
Inova Fairfax Hospital
Falls Church, Virginia, 22042
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Address
Naval Medical Center - Portsmouth
Portsmouth, Virginia, 23708-2197
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Address
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
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Address
Seattle Children's Hospital
Seattle, Washington, 98105
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Address
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
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Address
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
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Address
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
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Address
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
International Sites
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Sydney Children's Hospital
Randwick, New South Wales, 2031
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Address
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
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Address
Royal Children's Hospital
Parkville, Victoria, 3052
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Address
Princess Margaret Hospital for Children
Perth, Western Australia, 6008
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Address
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
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Address
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
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Address
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
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Address
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
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Address
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5
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Address
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
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Address
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
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Address
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
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Address
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
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Address
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
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Address
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Quebec, , G1V 4G2
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Address
San Jorge Children's Hospital
San Juan, , 00912
