A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)
- Conditions
- Anaplastic AstrocytomaDiffuse Midline Glioma, H3 K27M-MutantDiffuse Intrinsic Pontine GliomaAnaplastic Astrocytoma, Not Otherwise SpecifiedGlioblastoma, Not Otherwise SpecifiedMalignant GliomaGlioblastoma
- Interventions
- Procedure: Biopsy ProcedureProcedure: Magnetic Resonance ImagingRadiation: Radiation Therapy
- Registration Number
- NCT05099003
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase I/II trial tests the safety, side effects, and best dose of selinexor given in combination with standard radiation therapy in treating children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) with a genetic change called H3 K27M mutation. It also tests whether combination of selinexor and standard radiation therapy works to shrink tumors in this patient population. Glioma is a type of cancer that occurs in the brain or spine. Glioma is considered high risk (or high-grade) when it is growing and spreading quickly. The term, risk, refers to the chance of the cancer coming back after treatment. DIPG is a subtype of HGG that grows in the pons (a part of the brainstem that controls functions like breathing, swallowing, speaking, and eye movements). This trial has two parts. The only difference in treatment between the two parts is that some subjects treated in Part 1 may receive a different dose of selinexor than the subjects treated in Part 2. In Part 1 (also called the Dose-Finding Phase), investigators want to determine the dose of selinexor that can be given without causing side effects that are too severe. This dose is called the maximum tolerated dose (MTD). In Part 2 (also called the Efficacy Phase), investigators want to find out how effective the MTD of selinexor is against HGG or DIPG. Selinexor blocks a protein called CRM1, which may help keep cancer cells from growing and may kill them. It is a type of small molecule inhibitor called selective inhibitors of nuclear export (SINE). Radiation therapy uses high energy to kill tumor cells and shrink tumors. The combination of selinexor and radiation therapy may be effective in treating patients with newly-diagnosed DIPG and H3 K27M-Mutant HGG.
- Detailed Description
PRIMARY OBJECTIVES:
I. To define toxicities and estimate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of selinexor administered as an oral formulation in combination with standard of care radiation therapy (RT), to pediatric patients with newly diagnosed high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). (Dose-finding phase/phase I) II. To estimate the event-free survival (EFS) distribution for diffuse midline glioma (DMG)/HGG patients and overall survival (OS) distribution for DIPG patients associated with selinexor plus RT, followed by selinexor in patients with newly diagnosed HGG (H3 K27M mutant DMG or H3 K27-wild type HGG) or DIPG, and to compare those outcomes to historical controls. (Efficacy phase/phase II)
EXPLORATORY OBJECTIVE:
I. To bank tumor specimens and body fluids (blood and cerebrospinal fluid) for future studies.
OUTLINE: This is a phase I dose-escalation study of selinexor followed by a phase II study.
CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy 5 days per week for 5-7 weeks. Starting on day 4 or 5 of radiation therapy, patients receive selinexor orally (PO) on days 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity. After a 2-week rest period, patients proceed to Maintenance. Patients undergo a magnetic resonance imaging (MRI) and may undergo a biopsy during screening.
MAINTENANCE: Patients receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 24 cycles of maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients undergo a MRI on study and during follow-up.
After completion of study treatment, patients are followed every 3 months for year 1 (i.e., 3, 6, 9, 12 months), then every 6 months for years 2-3 (i.e., 18, 24, 30, 36 months), and finally once yearly for years 4-5 of this study.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 210
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PRE ENROLLMENT: Patients must be =< 25 years of age at the time of enrollment on APEC14B1 part A cnetral nervous system (CNS)/high grade glioma (HGG) pre-enrollment eligibility screening
-
Please note:
- This required age range applies to pre-enrollment eligibility for all HGG patients. Individual treatment protocols may have different age criteria.
- Non-DIPG patients with tumors that do not harbor an H3K27M-mutation and are >= 18 years of age will not be eligible to enroll on ACNS1821 (Step 1).
-
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PRE ENROLLMENT: Patient is suspected of having localized, newly diagnosed HGG, excluding metastatic disease, OR patient has an institutional diagnosis of DIPG
- Please note: there are specific radiographic criteria for DIPG patient enrollment on ACNS1821 (Step 1)
-
PRE ENROLLMENT:
- For patients with non-pontine tumors: Patients and/or their parents or legal guardians must have signed informed consent for eligibility screening on APEC14B1 Part A.
- For patients with DIPG: Patients and/or their parents or legal guardians must have signed informed consent for ACNS1821.
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PRE ENROLLMENT:
- For patients with non-pontine tumors only, the specimens obtained at the time of diagnostic biopsy or surgery must be submitted through APEC14B1 ASAP, preferably within 5 calendar days of definitive surgery
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STEP 1: Patients must be >= 12 months and =< 21 years of age at the time of enrollment
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STEP 1: Patients must have newly-diagnosed DIPG or HGG (including DMG).
-
STEP 1: Stratum DIPG
- Patients with newly-diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons on at least 1 axial T2 weighted image, are eligible. No histologic confirmation is required.
- Patients with pontine tumors that do not meet radiographic criteria for typical DIPG (e.g., focal tumors or those involving less than 2/3 of the pontine cross-sectional area with or without extrapontine extension) are eligible if the tumors are biopsied and proven to be high-grade gliomas (such as anaplastic astrocytoma, glioblastoma, high-grade glioma not otherwise specified [NOS], and/or H3 K27M-mutant) by institutional diagnosis.
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STEP 1: Stratum DMG (with H3 K27M mutation)
- Patients must have newly-diagnosed non-pontine H3 K27M-mutant HGG without BRAF V600 or IDH1 mutations as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1
- Note: Patients need not have either measurable or evaluable disease, i.e., DMG patients may have complete resection of their tumor prior to enrollment. Primary spinal tumors are eligible for enrollment. For rare H3 K27M-mutant HGG in non-midline structures (e.g., cerebral hemispheres), these patients will be considered part of Stratum DMG.
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STEP 1: Stratum HGG (without H3 K27M mutation)
-
Patients must have newly-diagnosed non-pontine H3 K27M-wild type HGG without BRAF V600 or IDH1 mutations as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1
-
Please note:
- Patients who fall in this category and who are >= 18 years of age are not eligible due to another standard-of-care regimen (radiation/temozolomide) that is available
- Patients need not have either measurable or evaluable disease, i.e., HGG patients may have complete resection of their tumor prior to enrollment. Primary spinal tumors are eligible for enrollment
-
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STEP 1: 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 who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
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STEP 1: Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to step 1 enrollment)
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STEP 1: Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to step 1 enrollment)
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STEP 1: Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days prior to step 1 enrollment)
-
STEP 1: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to step 1 enrollment) or
A serum creatinine based on age/gender as follows (within 7 days prior to step 1 enrollment):
-
Age / Maximum Serum Creatinine (mg/dL)
-
1 to < 2 years / male: 0.6; female: 0.6
-
2 to < 6 years / male: 0.8; female: 0.8
-
6 to < 10 years / male: 1; female: 1
-
10 to < 13 years / male: 1.2; female: 1.2
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13 to < 16 years / male: 1.5; female: 1.4
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>= 16 years / male: 1.7; female: 1.4
- STEP 1: Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
- STEP 1: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
- STEP 1: Serum amylase =< 1.5 x ULN
- STEP 1: Serum lipase =< 1.5 x ULN
- STEP 1: No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination.
- STEP 1: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
- STEP 1: Patients must be enrolled and protocol therapy must begin no later than 31 days after the date of radiographic diagnosis (in the case of non-biopsied DIPG patients only) or definitive surgery, whichever is the later date (Day 0).
-
For patients who have a biopsy followed by resection, the date of resection will be considered the date of definitive diagnostic surgery. If a biopsy only was performed, the biopsy date will be considered the date of definitive diagnostic surgery.
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STEP 1: Patients must not have received any prior therapy for their central nervous system (CNS) malignancy except for surgery and steroid medications.
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STEP 1: Patients who are currently receiving another investigational drug are not eligible.
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STEP 1: Patients who are currently receiving other anti-cancer agents are not eligible.
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STEP 1: Patients >=18 years of age who have H3 K27M-wild type HGG.
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STEP 1: Patients who have an uncontrolled infection.
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STEP 1: Patients who have received a prior solid organ transplantation.
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STEP 1: Patients with grade > 1 extrapyramidal movement disorder.
-
STEP 1: Patients with known macular degeneration, uncontrolled glaucoma, or cataracts.
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STEP 1: Patients with metastatic disease are not eligible; MRI of spine with and without contrast must be performed if metastatic disease is suspected by the treating physician.
-
STEP 1: Patients with gliomatosis cerebri type 1 or 2 are not eligible, with the exception of H3 K27M-mutant bithalamic tumors.
-
STEP 1: Patients who are not able to receive protocol specified radiation therapy.
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STEP 1:
- Female patients who are pregnant are ineligible since there is yet no available information regarding human fetal or teratogenic toxicities.
- Lactating females are not eligible unless they have agreed not to breastfeed their infants. It is not known whether selinexor is excreted in human milk.
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
- Sexually active patients of reproductive potential are not eligible unless they have agreed to use two effective methods of birth control (including a medically accepted barrier method of contraception, e.g., male or female condom) for the duration of their study participation and for 90 days after the last dose of selinexor. Abstinence is an acceptable method of birth control.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (selinexor and radiation therapy) Biopsy Procedure CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy 5 days per week for 5-7 weeks. Starting on day 4 or 5 of radiation therapy, patients receive selinexor PO on 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity. After a 2-week rest period, patients proceed to Maintenance. Patients undergo a MRI and may undergo a biopsy during screening. MAINTENANCE: Patients receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 24 cycles of maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients undergo a MRI on study and during follow-up. Treatment (selinexor and radiation therapy) Magnetic Resonance Imaging CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy 5 days per week for 5-7 weeks. Starting on day 4 or 5 of radiation therapy, patients receive selinexor PO on 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity. After a 2-week rest period, patients proceed to Maintenance. Patients undergo a MRI and may undergo a biopsy during screening. MAINTENANCE: Patients receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 24 cycles of maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients undergo a MRI on study and during follow-up. Treatment (selinexor and radiation therapy) Radiation Therapy CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy 5 days per week for 5-7 weeks. Starting on day 4 or 5 of radiation therapy, patients receive selinexor PO on 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity. After a 2-week rest period, patients proceed to Maintenance. Patients undergo a MRI and may undergo a biopsy during screening. MAINTENANCE: Patients receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 24 cycles of maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients undergo a MRI on study and during follow-up. Treatment (selinexor and radiation therapy) Selinexor CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy 5 days per week for 5-7 weeks. Starting on day 4 or 5 of radiation therapy, patients receive selinexor PO on 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity. After a 2-week rest period, patients proceed to Maintenance. Patients undergo a MRI and may undergo a biopsy during screening. MAINTENANCE: Patients receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 24 cycles of maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients undergo a MRI on study and during follow-up.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From the date of diagnosis until death date of any cause or last follow-up date, assessed up to 5 years Will be calculated for diffuse intrinsic pontine glioma (DIPG) patients. The OS curve will be estimated by Kaplan Meier estimates.
Overall response rate (ORR) Up to 5 years Defined as the proportion of patients whose best response is partial response or complete response.
Maximum tolerated dose From day 1 of selinexor treatment until the start of maintenance therapy, assessed up to 10 weeks from treatment start date Defined as the highest dose of selinexor in combination with standard of care radiation therapy (RT) that does not cause unacceptable side effects.
Event free survival (EFS) From the date of diagnosis until disease progression date, secondary malignant neoplasm occurrence date, death date of any cause, or last follow-up date, assessed up to 5 years Will be calculated for diffuse midline glioma (DMG)/ high grade glioma (HGG) patients. EFS curve will be estimated by Kaplan Meier estimates.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (123)
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
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, 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
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
🇺🇸Atlanta, Georgia, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Arnold Palmer Hospital for Children
🇺🇸Orlando, Florida, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Riley Hospital for Children
🇺🇸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
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
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
🇺🇸Grand Rapids, 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
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
Mercy Hospital Saint Louis
🇺🇸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
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, 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
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Legacy Emanuel Children's Hospital
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Prisma Health Richland Hospital
🇺🇸Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Saint Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
The Children's Hospital at TriStar Centennial
🇺🇸Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
El Paso Children's Hospital
🇺🇸El Paso, Texas, 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
Children's Hospital of San Antonio
🇺🇸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 Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, 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
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸Madison, Wisconsin, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Sydney Children's Hospital
🇦🇺Randwick, New South Wales, Australia
The Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Queensland Children's Hospital
🇦🇺South Brisbane, Queensland, Australia
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Perth Children's Hospital
🇦🇺Perth, Western Australia, Australia
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Hospital for Sick Children
🇨🇦Toronto, Ontario, 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
Jim Pattison Children's Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
🇨🇦Quebec, Canada
Starship Children's Hospital
🇳🇿Grafton, Auckland, New Zealand
Christchurch Hospital
🇳🇿Christchurch, New Zealand