Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations
Study Purpose
This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations. Poly adenosine diphosphate (ADP) ribose polymerases (PARPs) are proteins that help repair DNA mutations. PARP inhibitors, such as veliparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib, radiation therapy, and temozolomide may work better in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations compared to radiation therapy and temozolomide alone.
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 | 3 Years - 25 Years |
| Gender | All |
Inclusion Criteria:
- - Stratum 1 (IDH wild-type): Patients must be >= 3 years of age and =< 21 years of age at the time of enrollment.
- - Please note Stratum 1 was closed to accrual on January 24, 2020.
- - Stratum 2 (IDH mutant): Patients must be >= 3 years of age and =< 25 years of age at the time of enrollment.
- - Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1: - Newly-diagnosed high-grade glioma such as anaplastic astrocytoma or glioblastoma.
- - Negative results for H3 K27M by immunohistochemistry (IHC) - Negative results for BRAFV600 mutation by next-generation sequencing (NGS) - Patients must have histological verification of diagnosis.
- - Pre-operative and post-operative brain magnetic resonance imaging (MRI) with and without contrast must be obtained.
- - Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2.
- - Peripheral absolute neutrophil count (ANC) >= 1,000/uL (within 7 days prior to enrollment) - Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment) - Hemoglobin >= 8.0 gm/dL (can be transfused) (within 7 days prior to enrollment) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows (within 7 days prior to enrollment): - 3 to < 6 years: 0.8 (male and female) maximum serum creatinine (mg/dL) - 6 to < 10 years: 1 (male and female) maximum serum creatinine (mg/dL) - 10 to < 13 years: 1.2 (male and female) maximum serum creatinine (mg/dL) - 13 to < 16 years: 1.5 (male), 1.4 (female) maximum serum creatinine (mg/dL) - >= 16 years: 1.7 (male), 1.4 (female) maximum serum creatinine (mg/dL) - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L.
- - Patients with seizure disorder may be enrolled if seizures are well-controlled (i.e., patients must not have required rescue medications for uncontrolled seizures within 14 days prior to enrollment) - Patients must be enrolled and protocol therapy must be projected to begin no later than 31 days after definitive surgery (Day 0).
- - All patients and/or their parents or legal guardians must sign a written informed consent.
- - All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
- - Patients with the following histologies: - Diffuse astrocytoma (grade 2) - Oligodendrogliomas (any grade) - Pleomorphic xanthoastrocytoma (PXA, any grade) - Patients with primary tumor location of brainstem or spinal cord.
- - Patients with M+ disease (defined as neuraxis dissemination either by imaging or by cytology) - Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS) or with features suggestive of AML/MDS.
- - Prior allogenic bone marrow transplant or double umbilical cord blood transplantation.
- - Patients must not have received any prior tumor-directed therapy including radiation therapy, chemotherapy (tumor-directed therapy), molecularly targeted agents, or immunotherapy for the treatment of HGG other than surgical intervention and/or corticosteroids.
- - Lumbar CSF cytology is not required, but may be performed if clinically indicated prior to study enrollment.
- - Note: False positive cytology can occur within 10 days of surgery.
- - Patients with gliomatosis cerebri type 1 or 2.
- - Patients who are not able to receive protocol specified radiation therapy.
- - Patients must not be currently receiving other anti-cancer agents.
- - Patients with known constitutional mismatch repair deficiency syndrome (CMMR-D)/biallelic mismatch repair deficiency (bMMRD) - Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies.
- - Lactating females are not eligible unless they have agreed not to breastfeed their infants.
- - Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
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. |
NCT03581292 |
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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 2 |
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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. |
National Cancer Institute (NCI) |
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Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Matthias A Karajannis |
| 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. |
NIH |
| Overall Status | Active, not recruiting |
| Countries | Australia, Canada, New Zealand, Puerto Rico, United States |
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Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Anaplastic Astrocytoma, Glioblastoma, Malignant Glioma |
PRIMARY OBJECTIVES:
- I. To determine whether veliparib (ABT-888), when added to radiotherapy (RT) and temozolomide, is efficacious for the treatment of patients with newly-diagnosed high-grade glioma (HGG) whose tumors' molecular profile are wild-type for H3 K27M, BRAF, and IDH1/2.
- II. To determine whether veliparib (ABT-888), when added to RT and temozolomide, is efficacious for the treatment of patients with newly-diagnosed HGG whose tumors' molecular profile are wild-type for H3 K27M and BRAF and harbor an IDH1/2 mutation.
- I. To explore associations of genomic, transcriptomic, and/or epigenetic alterations of the tumors with treatment response and outcome.
- II. To explore the extent to which patients with BRCA1/2 gene alterations and other deoxyribonucleic acid (DNA) damaged genes display tumor genomic features consistent with homologous repair deficiency (HRD), including large scale state transitions (LSTs), mutational signature 3, and an enrichment for deletions flanked by sequences of (micro) homology.
- III. To explore the burden of high, moderate, and low penetrant germline alterations in HRD genes (such as BRCA1, BRCA2, PALB2, Fanconi complex genes, ATM, CHEK2, RAD51B/C/D), mis-match repair genes (such as MLH1, MSH2, MSH6, PMS2, EPCAM), and energy metabolism genes (such as SDHA, SDHB, SDHC, SDHAF2, SDHD, IDH1, IDH2, and FH).
- IV. To explore constitutional imprinting abnormalities associated with EP300 and IGF2 in peripheral blood from patients with HGGs.
Arms
Experimental: Treatment (radiation therapy, veliparib, temozolomide)
CHEMORADIOTHERAPY PHASE: Patients receive veliparib PO BID and undergo 30 daily fractions of radiation therapy 5 days per week for 6-7 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after chemoradiotherapy phase, patients receive veliparib PO BID and temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Interventions
Radiation: - Radiation Therapy
Undergo radiation therapy
Drug: - Temozolomide
Given PO
Drug: - Veliparib
Given PO
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
Address
Children's Hospital of Alabama
Birmingham, Alabama, 35233
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USA Health Strada Patient Care Center
Mobile, Alabama, 36604
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Banner Children's at Desert
Mesa, Arizona, 85202
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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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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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Mattel Children's Hospital UCLA
Los Angeles, California, 90095
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Valley Children's Hospital
Madera, California, 93636
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UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
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Kaiser Permanente-Oakland
Oakland, California, 94611
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Children's Hospital of Orange County
Orange, California, 92868
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Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
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Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502
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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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Yale University
New Haven, Connecticut, 06520
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Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
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MedStar Georgetown University Hospital
Washington, District of Columbia, 20007
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Children's National Medical Center
Washington, District of Columbia, 20010
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Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
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Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
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Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
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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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AdventHealth Orlando
Orlando, Florida, 32803
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Address
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
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Nemours Children's Hospital
Orlando, Florida, 32827
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Address
Johns Hopkins All Children's Hospital
Saint Petersburg, Florida, 33701
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Tampa General Hospital
Tampa, Florida, 33606
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Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
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Saint Mary's Medical Center
West Palm Beach, Florida, 33407
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Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
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Memorial Health University Medical Center
Savannah, Georgia, 31404
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Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
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Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
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Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
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University of Illinois
Chicago, Illinois, 60612
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Address
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
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Address
Loyola University Medical Center
Maywood, Illinois, 60153
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Saint Jude Midwest Affiliate
Peoria, Illinois, 61637
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Riley Hospital for Children
Indianapolis, Indiana, 46202
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Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260
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Blank Children's Hospital
Des Moines, Iowa, 50309
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University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
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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
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
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Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
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Eastern Maine Medical Center
Bangor, Maine, 04401
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Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
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Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
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Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
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Address
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
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UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655
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Address
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
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Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
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Henry Ford Health Saint John Hospital
Detroit, Michigan, 48236
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Address
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
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Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
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Corewell Health Children's
Royal Oak, Michigan, 48073
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Address
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
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University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
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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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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
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Address
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
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Address
University of Nebraska Medical Center
Omaha, Nebraska, 68198
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Address
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102
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Address
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109
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Address
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
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Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144
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Renown Regional Medical Center
Reno, Nevada, 89502
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Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
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Morristown Medical Center
Morristown, New Jersey, 07960
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Saint Peter's University Hospital
New Brunswick, New Jersey, 08901
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Albany Medical Center
Albany, New York, 12208
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Montefiore Medical Center - Moses Campus
Bronx, New York, 10467
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Roswell Park Cancer Institute
Buffalo, New York, 14263
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Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
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NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
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Memorial Sloan Kettering Cancer Center
New York, New York, 10065
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University of Rochester
Rochester, New York, 14642
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Address
State University of New York Upstate Medical University
Syracuse, New York, 13210
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New York Medical College
Valhalla, New York, 10595
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Mission Hospital
Asheville, North Carolina, 28801
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Address
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
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Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
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Duke University Medical Center
Durham, North Carolina, 27710
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Address
East Carolina University
Greenville, North Carolina, 27834
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Address
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
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Address
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
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Address
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
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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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Dayton Children's Hospital
Dayton, Ohio, 45404
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ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
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University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
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Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
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Oregon Health and Science University
Portland, Oregon, 97239
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Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
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Geisinger Medical Center
Danville, Pennsylvania, 17822
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Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
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Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
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Rhode Island Hospital
Providence, Rhode Island, 02903
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Medical University of South Carolina
Charleston, South Carolina, 29425
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Prisma Health Richland Hospital
Columbia, South Carolina, 29203
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BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
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Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
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T C Thompson Children's Hospital
Chattanooga, Tennessee, 37403
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East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
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Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
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Address
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
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Address
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
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Address
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
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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
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
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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
M D Anderson Cancer Center
Houston, Texas, 77030
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Address
Children's Hospital of San Antonio
San Antonio, Texas, 78207
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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
Scott and White Memorial Hospital
Temple, Texas, 76508
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Address
Primary Children's Hospital
Salt Lake City, Utah, 84113
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Address
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
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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
Madigan Army Medical Center
Tacoma, Washington, 98431
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Address
West Virginia University Healthcare
Morgantown, West Virginia, 26506
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Address
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
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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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John Hunter Children's Hospital
Hunter Regional Mail Centre, New South Wales, 2310
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Address
Sydney Children's Hospital
Randwick, New South Wales, 2031
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The Children's Hospital at Westmead
Westmead, New South Wales, 2145
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Address
Queensland Children's Hospital
South Brisbane, Queensland, 4101
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Address
Monash Medical Center-Clayton Campus
Clayton, Victoria, 3168
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Address
Royal Children's Hospital
Parkville, Victoria, 3052
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Address
Perth Children's Hospital
Perth, Western Australia, 6009
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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
Janeway Child Health Centre
Saint John's, Newfoundland and Labrador, A1B 3V6
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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
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
Status
Address
Starship Children's Hospital
Grafton, Auckland, 1145
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Address
Christchurch Hospital
Christchurch, , 8011
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Address
HIMA San Pablo Oncologic Hospital
Caguas, , 00726
