A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
- Conditions
- Low Grade AstrocytomaMetastatic Low Grade GliomaLow Grade GliomaMetastatic Low Grade Astrocytoma
- Interventions
- Procedure: Biospecimen CollectionProcedure: Magnetic Resonance ImagingOther: Quality-of-Life AssessmentOther: Questionnaire Administration
- Registration Number
- NCT04166409
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase III trial compares the effect of selumetinib versus the standard of care treatment with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously untreated low-grade glioma (LGG) that does not have a genetic abnormality called BRAFV600E mutation and is not associated with systemic neurofibromatosis type 1. Selumetinib works by blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin and vincristine are chemotherapy drugs that work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. The overall goal of this study is to see if selumetinib works just as well as the standard treatment of CV for patients with LGG. Another goal of this study is to compare the effects of selumetinib versus CV in subjects with LGG to find out which is better. Additionally, this trial will also examine if treatment with selumetinib improves the quality of life for subjects who take it.
- Detailed Description
PRIMARY OBJECTIVE:
I. To demonstrate that the efficacy of treatment with selumetinib as measured by event-free survival (EFS) is non-inferior compared to treatment with carboplatin/vincristine (CV) in previously-untreated low-grade glioma (LGG) not associated with BRAFV600E mutations or systemic neurofibromatosis type 1 (NF1).
SECONDARY OBJECTIVES:
I. To estimate tumor response rates to each regimen of chemotherapy. II. To evaluate visual acuity (VA) outcomes utilizing Teller Acuity Cards (TAC) and HOTV letter acuity testing in previously-untreated optic pathway gliomas (OPGs).
III. To describe the improvement in motor function as measured by the Vineland Scale in children with previously-untreated LGG that have motor deficits at enrollment.
IV. To estimate the difference in EFS and tumor response rate between BRAF rearranged and non-BRAF rearranged patients treated on each chemotherapy regimen.
V. To prospectively evaluate the quality of life of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib.
VI. To prospectively evaluate the cognitive, social, emotional, and behavioral functioning of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib.
EXPLORATORY OBJECTIVE:
I. To obtain paired blood and tumor specimens for future biology studies as well as data from Molecular Characterization Initiative (MCI) testing, to correlate genomic drivers to efficacy outcomes.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I:
INDUCTION: Patients receive vincristine sulfate intravenously (IV) on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) at baseline and end of induction.
MAINTENANCE: Patients receive vincristine sulfate IV on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up.
ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up.
After completion of study treatment, patients are followed up every 3 months for year 1, every 6 months for years 2-3, and then annually for years 4-10.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 220
-
Patients must be >= 2 years and =< 21 years at the time of enrollment
-
Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
-
Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 (NCT02402244) Childhood Cancer Data Initiative (CCDI)-MCI, or accepted Clinical Laboratory Improvement Amendments (CLIA)-certified test and that has not been treated with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously diagnosed, and there is no required time frame between biopsy/surgery and treatment initiation.
- Patients with residual tumor after resection or progressive tumor after initial diagnosis (with or without surgery) who have not received treatment (chemotherapy and/or radiation) are eligible
- Patients must have two-dimensional measurable tumor >= 1 cm^2 to be eligible
- Patients with ependymoma are not eligible
-
Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization [WHO] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
-
Patients with metastatic disease or multiple independent primary LGG are eligible
-
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/sex as follows (performed within 7 days prior to enrollment):
- Age: Maximum Serum Creatinine (mg/dL)
- 2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female)
- 6 to < 10 years: 1 mg/dL (male); 1 mg/dL (female)
- 10 to < 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female)
- 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
- >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
-
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect [unconjugated] bilirubin levels as long as their direct [conjugated] bilirubin is < 3.1 mg/dL)
-
Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
-
Albumin >= 2 g/dL (performed within 7 days prior to enrollment)
-
Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (performed within 4 weeks prior to enrollment)
-
Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (performed within 4 weeks prior to enrollment)
-
Absolute neutrophil count >= 1,000/uL (unsupported) (performed within 7 days prior to enrollment)
-
Platelets >= 100,000/uL (unsupported) (performed within 7 days prior to enrollment)
-
Hemoglobin >= 8 g/dL (may be supported) (performed within 7 days prior to enrollment)
-
Patients with a known seizure disorder must be stable and must not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
-
Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for age, height, and sex at the time of enrollment (with or without the use of anti-hypertensive medications)
-
Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)
-
Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension
-
All patients must have ophthalmology toxicity assessments performed within 8 weeks prior to enrollment
-
For all patients, a magnetic resonance imaging (MRI) of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 8 weeks prior to enrollment
-
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
-
Patients must have the ability to swallow whole capsules
-
All patients have signed an appropriate consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization form (if applicable)
-
All patients and/or their parents or legal guardians must sign a written informed consent
-
All patients have been consented and enrolled on APEC14B1 (NCT02402244) followed by enrollment on the ACNS1833 Pre-Enrollment Eligibility Screening (Step 0) on the same day to complete the Rapid Central Review
-
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
-
Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention (with the exclusion of laser interstitial thermal therapy [LITT]) is permitted
-
Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
-
Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
-
Patients may not be receiving any other investigational agents
-
Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment
-
Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
-
Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
-
Lactating females who plan to breastfeed their infants are not eligible
-
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible.
- Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
-
Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented
-
Symptomatic heart failure
-
New York Health Association (NYHA) class II-IV prior or current cardiomyopathy
-
Severe valvular heart disease
-
History of atrial fibrillation
-
Current or past history of central serous retinopathy
-
Current or past history of retinal vein occlusion or retinal detachment
-
Patients with uncontrolled glaucoma
- If checking pressure is clinically indicated, patients with intraocular pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
-
Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
-
Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy, placement of a vascular access device or cerebral spinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt.
- Note: Patients must have healed from any prior surgery
-
Patients who have an uncontrolled infection are not eligible
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (vincristine sulfate, carboplatin) Biospecimen Collection INDUCTION: Patients receive vincristine sulfate IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) at baseline and end of induction. MAINTENANCE: Patients receive vincristine sulfate IV on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up. Arm I (vincristine sulfate, carboplatin) Carboplatin INDUCTION: Patients receive vincristine sulfate IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) at baseline and end of induction. MAINTENANCE: Patients receive vincristine sulfate IV on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up. Arm I (vincristine sulfate, carboplatin) Magnetic Resonance Imaging INDUCTION: Patients receive vincristine sulfate IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) at baseline and end of induction. MAINTENANCE: Patients receive vincristine sulfate IV on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up. Arm I (vincristine sulfate, carboplatin) Quality-of-Life Assessment INDUCTION: Patients receive vincristine sulfate IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) at baseline and end of induction. MAINTENANCE: Patients receive vincristine sulfate IV on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up. Arm I (vincristine sulfate, carboplatin) Questionnaire Administration INDUCTION: Patients receive vincristine sulfate IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) at baseline and end of induction. MAINTENANCE: Patients receive vincristine sulfate IV on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up. Arm I (vincristine sulfate, carboplatin) Vincristine Sulfate INDUCTION: Patients receive vincristine sulfate IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) at baseline and end of induction. MAINTENANCE: Patients receive vincristine sulfate IV on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up. Arm II (selumetinib sulfate) Biospecimen Collection Patients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up. Arm II (selumetinib sulfate) Magnetic Resonance Imaging Patients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up. Arm II (selumetinib sulfate) Quality-of-Life Assessment Patients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up. Arm II (selumetinib sulfate) Questionnaire Administration Patients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up. Arm II (selumetinib sulfate) Selumetinib Sulfate Patients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo MRI at baseline, throughout the trial, and during follow up.
- Primary Outcome Measures
Name Time Method Event-free survival (EFS) Up to 10 years from date of randomization The Kaplan-Meier method will be used to estimate EFS which is defined as the interval from randomization to first occurrence of clinical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause, or to the date of last follow-up. Estimates with 95% confidence intervals will be reported by treatment arm. The hazard ratio with a confidence interval will also be reported to compare treatment arms based on a Cox proportional hazards model stratified by BRAF status, tumor location and size of residual tumor. Will also provide outcome estimates and their associated confidence intervals by sex, race and ethnicity, as descriptive summaries of outcome.
- Secondary Outcome Measures
Name Time Method Radiographic tumor response rate Up to 10 years Percentages of patients with responses (complete or partial response) will be reported by treatment arm with 95% confidence intervals. The result of an exact binomial test to test for the difference in response rates between treatment arm will also be reported. Will also provide outcome estimates and their associated confidence intervals by sex, race and ethnicity, as descriptive summaries of outcome.
Overall survival (OS) Up to 10 years from date of randomization The Kaplan-Meier method will be used to estimate OS by treatment arm, defined as the interval from randomization to death from any cause, or to the date of last follow-up. Estimates with confidence intervals will be reported by treatment arm. Will also provide outcome estimates and their associated confidence intervals by sex, race and ethnicity, as descriptive summaries of outcome.
Number of patients who experience an improvement in visual acuity (VA) After the first 12 months of treatment Numbers of patients that show improvement in VA after 12 months of treatment will be reported by treatment arm. Patients with at least 1 impaired eye are evaluable. In a patient with a unilateral optic nerve glioma, only the affected eye is considered. In patients with bilateral visual impairment, if VA improves in 1 eye but worsens in the other, the patient will be coded as a treatment failure, whereas if 1 eye improves and the other is at least stable, the patient will be coded as a success.
Change in motor function After 48 weeks of therapy Motor function is measured using the Vineland-3 Motor Scale. Only patients with motor function deficits at baseline are included. Magnitudes of change for each patient after 48 weeks of therapy from baseline will be calculated and medians (with ranges) by treatment arm will be reported.
Change in quality of life (QOL) Baseline and 9 months after treatment initiation QOL will be measured using the PedsQL Total Scale Score as measured from the validated PedsQL Generic Module (for children 2-21 years old). Mean differences in the total scale score between 9 months and baseline will be reported by treatment arm. The results of 2-sample t-test comparing differences in the QOL scores between the 2 arms will also be reported. If change scores do not follow normal distributions, non-parametric alternatives may be employed for analysis.
Processing speed function Up to 9 months post-treatment initiation Measured by Wechsler Processing Speed Index (standard score). Scores at 9 months will be summarized by treatment arm and reported as means (with standard deviations) or medians (with ranges) depending on the data distribution.
Change in executive function Baseline and 9-months Executive function will be measured by the Behavior Rating Inventory of Executive Function, Second Edition BRIEF Cognitive Regulation Index (CRI). Summary statistics for the differences in scores from baseline to 9 months will be reported by treatment arm.
Trial Locations
- Locations (130)
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Banner Children's at Desert
🇺🇸Mesa, Arizona, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Mattel Children's Hospital UCLA
🇺🇸Los Angeles, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Arnold Palmer Hospital for Children
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Sacred Heart Hospital
🇺🇸Pensacola, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
🇺🇸Atlanta, Georgia, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Ascension Saint Vincent Indianapolis Hospital
🇺🇸Indianapolis, Indiana, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Maine Children's Cancer Program
🇺🇸Scarborough, Maine, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Corewell Health Children's
🇺🇸Royal Oak, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
NYU Langone Hospital - Long Island
🇺🇸Mineola, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
New York Medical College
🇺🇸Valhalla, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Prisma Health Richland Hospital
🇺🇸Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Saint Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
El Paso Children's Hospital
🇺🇸El Paso, Texas, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
UMC Cancer Center / UMC Health System
🇺🇸Lubbock, Texas, United States
Children's Hospital of San Antonio
🇺🇸San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
University of Vermont and State Agricultural College
🇺🇸Burlington, Vermont, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Carilion Children's
🇺🇸Roanoke, Virginia, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸Tacoma, Washington, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸Madison, Wisconsin, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Janeway Child Health Centre
🇨🇦Saint John's, Newfoundland and Labrador, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
The Montreal Children's Hospital of the MUHC
🇨🇦Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
🇨🇦Quebec, Canada
HIMA San Pablo Oncologic Hospital
🇵🇷Caguas, Puerto Rico