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Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
Study Purpose
This phase II Pediatric MATCH trial studies how well ulixertinib works in treating patients with solid tumors that have spread to other places in the body (advanced), non-Hodgkin lymphoma, or histiocytic disorders that have a genetic alteration (mutation) in a signaling pathway called MAPK. A signaling pathway consists of a group of molecules in a cell that control one or more cell functions. Genes in the MAPK pathway are frequently mutated in many types of cancers. Ulixertinib may stop the growth of cancer cells that have mutations in the MAPK pathway.
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 | 12 Months - 21 Years |
| Gender | All |
Inclusion Criteria:
- - Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621J based on the presence of an actionable mutation.
- - Patients must have a body surface area >= 0.54 m^2 at the time of study enrollment.
- - Patients must have radiographically measurable disease at the time of study enrollment.
- - Note: The following do not qualify as measurable disease: - Malignant fluid collections (e.g., ascites, pleural effusions) - Bone marrow infiltration except that detected by MIBG scan for neuroblastoma.
- - Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma.
- - Elevated tumor markers in plasma or cerebrospinal fluid (CSF) - Previously radiated lesions that have not demonstrated clear progression post radiation.
- - Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- - Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age.
- - Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.
- - Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
- - >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea).
- - Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): >= 7 days after the last dose of agent.
- - Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1.
- - Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid.
- - Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor.
- - Interleukins, Interferons and Cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors).
- - Stem cell Infusions (with or without total body irradiation [TBI]): - Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including DLI or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD).
- - Autologous stem cell infusion including boost infusion: >= 42 days.
- - Cellular Therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.).
- - Radiotherapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial brain metastases (BM) radiation.
- - Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment.
- - Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy.
- - Patients must not have received prior exposure to BVD-523FB (ulixertinib) or other ERK inhibitors.
- - For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment).
- - For patients with solid tumors without known bone marrow involvement: Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
- - Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions).
- - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2, or (within 7 days prior to enrollment).
- - A serum creatinine based on age/gender (within 7 days prior to enrollment).
- - Age 1 to < 2 years, maximum serum creatinine (mg/dL) male 0.6, female 0.6.
- - Age 2 to < 6 years, maximum serum creatinine (mg/dL) male 0.8, female 0.8.
- - Age 6 to < 10 years, maximum serum creatinine (mg/dL) male 1, female 1.
- - Age 10 to < 13 years, maximum serum creatinine (mg/dL) male 1.2, female 1.2.
- - Age 13 to < 16 years, maximum serum creatinine (mg/dL) male 1.5, female 1.4.
- - Age >= 16 years, maximum serum creatinine (mg/dL) male 1.7, female 1.4.
- - Bilirubin (sum of conjugated + unconjugated) =< 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.
- - Serum albumin >= 2 g/dL (within 7 days prior to enrollment).
- - Shortening fraction of >= 27% by echocardiogram, or (within 7 days prior to enrollment).
- - Ejection fraction of >= 50% by gated radionuclide study (within 7 days prior to enrollment).
- - QTc interval =< 480 milliseconds (within 7 days prior to enrollment).
- - Patients must be able to swallow intact capsules.
- - All patients and/or their parents or legally authorized representatives must sign a written informed consent.
Exclusion Criteria:
- - Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies.
- - Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
- - Patients who are currently receiving another investigational drug are not eligible.
- - Patients who are currently receiving other anti-cancer agents are not eligible.
- - Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
- - Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible.
- - Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP1A2 and CYP2D6 are not eligible.
- - Patients with known significant ophthalmologic conditions (uncontrolled glaucoma, history of retinal vein occlusion or retinal detachment, excluding patients with longstanding findings secondary to existing conditions) are not eligible.
- - Patients who have an uncontrolled infection are not eligible.
- - Patients who have received a prior solid organ transplantation are not eligible.
- - Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
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. |
NCT03698994 |
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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. |
Kieuhoa T Vo |
| 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 | Puerto Rico, United States |
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Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Advanced Malignant Solid Neoplasm, Recurrent Ependymal Tumor, Recurrent Ewing Sarcoma, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Histiocytic and Dendritic Cell Neoplasm, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Primary Malignant Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Refractory Ependymoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Histiocytic and Dendritic Cell Neoplasm, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Primary Malignant Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Wilms Tumor |
PRIMARY OBJECTIVES:
- I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with BVD-523FB (ulixertinib) with advanced solid tumors (including central nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in the MAPK pathway.
- I. To estimate the progression free survival in pediatric patients treated with BVD-523FB (ulixertinib) with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in the MAPK pathway.
- II. To obtain information about the tolerability of BVD-523FB (ulixertinib) in children and adolescents with relapsed or refractory cancer.
- III. To provide preliminary estimates of the pharmacokinetics of BVD-523FB (ulixertinib) in children and adolescents with relapsed or refractory cancer.
- I. To evaluate other biomarkers as predictors of response to BVD-523FB (ulixertinib) and specifically, whether tumors that harbor different mutations or fusions will demonstrate differential response to BVD-523FB (ulixertinib) treatment.
- II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
Arms
Experimental: Treatment (ulixertinib)
Patients receive ulixertinib PO BID. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Interventions
Other: - Pharmacokinetic Study
Ancillary studies
Drug: - Ulixertinib
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 4049979, Alabama 4829764, 35233
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Address
Providence Alaska Medical Center
Anchorage 5879400, Alaska 5879092, 99508
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Address
Banner Children's at Desert
Mesa 5304391, Arizona 5551752, 85202
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Address
Banner University Medical Center - Tucson
Tucson 5318313, Arizona 5551752, 85719
Status
Address
Arkansas Children's Hospital
Little Rock 4119403, Arkansas 4099753, 72202-3591
Status
Address
Kaiser Permanente Downey Medical Center
Downey 5343858, California 5332921, 90242
Status
Address
Loma Linda University Medical Center
Loma Linda 5367696, California 5332921, 92354
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Address
Miller Children's and Women's Hospital Long Beach
Long Beach 5367929, California 5332921, 90806
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Address
Children's Hospital Los Angeles
Los Angeles 5368361, California 5332921, 90027
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Address
Mattel Children's Hospital UCLA
Los Angeles 5368361, California 5332921, 90095
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Address
Valley Children's Hospital
Madera 5369568, California 5332921, 93636
Status
Address
UCSF Benioff Children's Hospital Oakland
Oakland 5378538, California 5332921, 94609
Status
Address
Kaiser Permanente-Oakland
Oakland 5378538, California 5332921, 94611
Status
Address
UCSF Medical Center-Mission Bay
San Francisco 5391959, California 5332921, 94158
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Address
Children's Hospital Colorado
Aurora 5412347, Colorado 5417618, 80045
Status
Address
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver 5419384, Colorado 5417618, 80218
Status
Address
Alfred I duPont Hospital for Children
Wilmington 4145381, Delaware 4142224, 19803
Status
Address
Children's National Medical Center
Washington D.C. 4140963, District of Columbia 4138106, 20010
Status
Address
University of Florida Health Science Center - Gainesville
Gainesville 4156404, Florida 4155751, 32610
Status
Address
Nemours Children's Clinic-Jacksonville
Jacksonville 4160021, Florida 4155751, 32207
Status
Address
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami 4164138, Florida 4155751, 33136
Status
Address
Nicklaus Children's Hospital
Miami 4164138, Florida 4155751, 33155
Status
Address
AdventHealth Orlando
Orlando 4167147, Florida 4155751, 32803
Status
Address
Arnold Palmer Hospital for Children
Orlando 4167147, Florida 4155751, 32806
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Address
Nemours Children's Hospital
Orlando 4167147, Florida 4155751, 32827
Status
Address
Johns Hopkins All Children's Hospital
St. Petersburg 4171563, Florida 4155751, 33701
Status
Address
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa 4174757, Florida 4155751, 33607
Status
Address
Saint Mary's Medical Center
West Palm Beach 4177887, Florida 4155751, 33407
Status
Address
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta 4180439, Georgia 4197000, 30329
Status
Address
Memorial Health University Medical Center
Savannah 4221552, Georgia 4197000, 31404
Status
Address
Saint Luke's Cancer Institute - Boise
Boise 5586437, Idaho 5596512, 83712
Status
Address
University of Chicago Comprehensive Cancer Center
Chicago 4887398, Illinois 4896861, 60637
Status
Address
Saint Jude Midwest Affiliate
Peoria 4905687, Illinois 4896861, 61637
Status
Address
Southern Illinois University School of Medicine
Springfield 4250542, Illinois 4896861, 62702
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Address
Riley Hospital for Children
Indianapolis 4259418, Indiana 4921868, 46202
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Address
Ascension Saint Vincent Indianapolis Hospital
Indianapolis 4259418, Indiana 4921868, 46260
Status
Address
Blank Children's Hospital
Des Moines 4853828, Iowa 4862182, 50309
Status
Address
University of Iowa/Holden Comprehensive Cancer Center
Iowa City 4862034, Iowa 4862182, 52242
Status
Address
Children's Hospital New Orleans
New Orleans 4335045, Louisiana 4331987, 70118
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Address
Ochsner Medical Center Jefferson
New Orleans 4335045, Louisiana 4331987, 70121
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Address
Eastern Maine Medical Center
Bangor 4957280, Maine 4971068, 04401
Status
Address
Sinai Hospital of Baltimore
Baltimore 4347778, Maryland 4361885, 21215
Status
Address
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore 4347778, Maryland 4361885, 21287
Status
Address
Massachusetts General Hospital Cancer Center
Boston 4930956, Massachusetts 6254926, 02114
Status
Address
Dana-Farber Cancer Institute
Boston 4930956, Massachusetts 6254926, 02215
Status
Address
C S Mott Children's Hospital
Ann Arbor 4984247, Michigan 5001836, 48109
Status
Address
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids 4994358, Michigan 5001836, 49503
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Address
Bronson Methodist Hospital
Kalamazoo 4997787, Michigan 5001836, 49007
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Address
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis 5037649, Minnesota 5037779, 55404
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Address
University of Minnesota/Masonic Cancer Center
Minneapolis 5037649, Minnesota 5037779, 55455
Status
Address
University of Mississippi Medical Center
Jackson 4431410, Mississippi 4436296, 39216
Status
Address
Children's Mercy Hospitals and Clinics
Kansas City 4393217, Missouri 4398678, 64108
Status
Address
Cardinal Glennon Children's Medical Center
St Louis 4407066, Missouri 4398678, 63104
Status
Address
Washington University School of Medicine
St Louis 4407066, Missouri 4398678, 63110
Status
Address
Mercy Hospital Saint Louis
St Louis 4407066, Missouri 4398678, 63141
Status
Address
Children's Hospital and Medical Center of Omaha
Omaha 5074472, Nebraska 5073708, 68114
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Address
University of Nebraska Medical Center
Omaha 5074472, Nebraska 5073708, 68198
Status
Address
Hackensack University Medical Center
Hackensack 5098706, New Jersey 5101760, 07601
Status
Address
Morristown Medical Center
Morristown 5101427, New Jersey 5101760, 07960
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Address
Saint Peter's University Hospital
New Brunswick 5101717, New Jersey 5101760, 08901
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Address
Albany Medical Center
Albany 5106834, New York 5128638, 12208
Status
Address
Roswell Park Cancer Institute
Buffalo 5110629, New York 5128638, 14263
Status
Address
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park 5128514, New York 5128638, 11040
Status
Address
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York 5128581, New York 5128638, 10016
Status
Address
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York 5128581, New York 5128638, 10032
Status
Address
Memorial Sloan Kettering Cancer Center
New York 5128581, New York 5128638, 10065
Status
Address
NYP/Weill Cornell Medical Center
New York 5128581, New York 5128638, 10065
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Address
University of Rochester
Rochester 5134086, New York 5128638, 14642
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Address
State University of New York Upstate Medical University
Syracuse 5140405, New York 5128638, 13210
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Address
Mission Hospital
Asheville 4453066, North Carolina 4482348, 28801
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Address
Carolinas Medical Center/Levine Cancer Institute
Charlotte 4460243, North Carolina 4482348, 28203
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Address
Duke University Medical Center
Durham 4464368, North Carolina 4482348, 27710
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Address
Cincinnati Children's Hospital Medical Center
Cincinnati 4508722, Ohio 5165418, 45229
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Address
Nationwide Children's Hospital
Columbus 4509177, Ohio 5165418, 43205
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Address
Dayton Children's Hospital
Dayton 4509884, Ohio 5165418, 45404
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Address
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo 5174035, Ohio 5165418, 43606
Status
Address
University of Oklahoma Health Sciences Center
Oklahoma City 4544349, Oklahoma 4544379, 73104
Status
Address
Legacy Emanuel Children's Hospital
Portland 5746545, Oregon 5744337, 97227
Status
Address
Oregon Health and Science University
Portland 5746545, Oregon 5744337, 97239
Status
Address
Geisinger Medical Center
Danville 5186327, Pennsylvania 6254927, 17822
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Address
Children's Hospital of Philadelphia
Philadelphia 4560349, Pennsylvania 6254927, 19104
Status
Address
Children's Hospital of Pittsburgh of UPMC
Pittsburgh 5206379, Pennsylvania 6254927, 15224
Status
Address
BI-LO Charities Children's Cancer Center
Greenville 4580543, South Carolina 4597040, 29605
Status
Address
Sanford USD Medical Center - Sioux Falls
Sioux Falls 5231851, South Dakota 5769223, 57117-5134
Status
Address
East Tennessee Childrens Hospital
Knoxville 4634946, Tennessee 4662168, 37916
Status
Address
Saint Jude Children's Research Hospital
Memphis 4641239, Tennessee 4662168, 38105
Status
Address
Vanderbilt University/Ingram Cancer Center
Nashville 4644585, Tennessee 4662168, 37232
Status
Address
Dell Children's Medical Center of Central Texas
Austin 4671654, Texas 4736286, 78723
Status
Address
Medical City Dallas Hospital
Dallas 4684888, Texas 4736286, 75230
Status
Address
UT Southwestern/Simmons Cancer Center-Dallas
Dallas 4684888, Texas 4736286, 75390
Status
Address
Cook Children's Medical Center
Fort Worth 4691930, Texas 4736286, 76104
Status
Address
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston 4699066, Texas 4736286, 77030
Status
Address
M D Anderson Cancer Center
Houston 4699066, Texas 4736286, 77030
Status
Address
Children's Hospital of San Antonio
San Antonio 4726206, Texas 4736286, 78207
Status
Address
Methodist Children's Hospital of South Texas
San Antonio 4726206, Texas 4736286, 78229
Status
Address
Scott and White Memorial Hospital
Temple 4735966, Texas 4736286, 76508
Status
Address
Primary Children's Hospital
Salt Lake City 5780993, Utah 5549030, 84113
Status
Address
University of Vermont and State Agricultural College
Burlington 5234372, Vermont 5242283, 05405
Status
Address
Children's Hospital of The King's Daughters
Norfolk 4776222, Virginia 6254928, 23507
Status
Address
VCU Massey Comprehensive Cancer Center
Richmond 4781708, Virginia 6254928, 23298
Status
Address
Seattle Children's Hospital
Seattle 5809844, Washington 5815135, 98105
Status
Address
Providence Sacred Heart Medical Center and Children's Hospital
Spokane 5811696, Washington 5815135, 99204
Status
Address
Madigan Army Medical Center
Tacoma 5812944, Washington 5815135, 98431
Status
Address
University of Wisconsin Carbone Cancer Center - University Hospital
Madison 5261457, Wisconsin 5279468, 53792
Status
Address
Children's Hospital of Wisconsin
Milwaukee 5263045, Wisconsin 5279468, 53226
International Sites
Status
Address
San Jorge Children's Hospital
San Juan 4568127, , 00912
Status
Address
University Pediatric Hospital
San Juan 4568127, , 00926
