A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT

Phase 2

Recruiting

• Conditions: Embryonal Carcinoma; Malignant Teratoma; Choriocarcinoma; Mixed Germ Cell Tumor; Pineal Region Germ Cell Tumor; Central Nervous System Nongerminomatous Germ Cell Tumor; Immature Teratoma; Suprasellar Germ Cell Tumor; Pineal Region Immature Teratoma; Pineal Region Yolk Sac Tumor
• Interventions: Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Etoposide; Biological: Filgrastim; Drug: Ifosfamide; Procedure: Magnetic Resonance Imaging; Drug: Mesna; Biological: Pegfilgrastim; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Questionnaire Administration; Radiation: Radiation Therapy; Procedure: Second-Look Surgery; Drug: Thiotepa

• Registration Number: NCT04684368
• Lead Sponsor: Children's Oncology Group

Brief Summary

This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond we...

Detailed Description

PRIMARY OBJECTIVES:
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-12-15
• Study First Submitted QC: 2020-12-22
• Study First Posted: 2020-12-24
• Study Start: 2021-07-13
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-02
• Last Update Posted: 2024-12-04
• Primary Completion: 2029-12-21
• Study Completion: 2029-12-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

• Patients must be >= 3 years and < 30 years at the time of study enrollment

• Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG) beta > 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers and cytology must be within 31 days prior to enrollment and start of protocol therapy [repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days prior to enrollment and start of protocol therapy [repeat if necessary]). Basal ganglia or other primary sites are excluded

• Patients with any of the following pathological elements are eligible: endodermal sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant elements listed above are present. Patients with only mature teratoma are excluded. Patients with pure germinoma admixed with mature teratoma are excluded (would be eligible for pure germinoma protocols)

• Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post operative brain MRI with and without gadolinium. The post operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required (within 31 days prior to study enrollment and start of protocol therapy )

• Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior to study enrollment and start of protocol therapy)

• Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery

• Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior to enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first

• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment)

• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)

• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (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):

  • Age: Maximum serum creatinine (mg/dL)

    • 3 to < 6 years: 0.8 (male), 0.8 (female)
    • 6 to < 10 years: 1 (male), 1 (female)
    • 10 to < 13 years: 1.2 (male), 1.2 (female)
    • 13 to < 16 years: 1.5 (male), 1.4 (female)
    • >= 16 years: male (1.7), 1.4 (female)

• 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 (within 7 days prior to enrollment)

  • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L

• Central nervous system function defined as:

  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
  • Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment

• Protocol therapy must begin within 31 calendar days of definitive surgery or clinical diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.

• 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

• NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:

• English-, Spanish-, or French- speaking

  • Note: Patients who speak a language other than English, Spanish, or French will be allowed to participate in ACNS2021 but will not complete the neurocognitive and quality of life assessments

• No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g., Down syndrome, fragile X, William syndrome, intellectual disability). Patients with NF1 will be allowed to participate

• Additional eligibility criteria for the COG Standardized Neuropsychological Battery only: must be at a site that has a psychologist to administer the battery

  • Note: If not eligible for the COG Standardized Battery, patients should still complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior Assessment System Third Edition (ABAS-3), and Behavior Assessment System for Children, Third Edition (BASC-3) questionnaires

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Exclusion Criteria

• Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)

• Patients with only mature teratoma and non-elevated markers upon tumor sampling at diagnosis

• Patients who have received any prior tumor-directed therapy for their diagnosis of NGGCT other than surgical intervention and corticosteroids

• Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or intraoperative evidence of dissemination)

• Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs

  • Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards

• Lactating females who plan to breastfeed their infants

• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Carboplatin	See Outline in Detailed Description.
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Pegfilgrastim	See Outline in Detailed Description.
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Filgrastim	See Outline in Detailed Description.
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Biospecimen Collection	See Outline in Detailed Description.
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Ifosfamide	See Outline in Detailed Description.
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Magnetic Resonance Imaging	See Outline in Detailed Description.
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Mesna	See Outline in Detailed Description.
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Second-Look Surgery	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Questionnaire Administration	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Second-Look Surgery	See Outline in Detailed Description.
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Questionnaire Administration	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Biospecimen Collection	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Carboplatin	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Magnetic Resonance Imaging	See Outline in Detailed Description.
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Radiation Therapy	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Ifosfamide	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Thiotepa	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Radiation Therapy	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Peripheral Blood Stem Cell Transplantation	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Etoposide	See Outline in Detailed Description.
Plan A (chemotherapy, WVSCI, second-look surgery if needed)	Etoposide	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Filgrastim	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Mesna	See Outline in Detailed Description.
Plan B (chemotherapy, HDCSCR, second-look surgery if needed)	Pegfilgrastim	See Outline in Detailed Description.

Primary Outcome Measures

Name	Time	Method
Spinal failure rate	Within 2 years of enrollment	Will be measured by the number of spinal relapses (spine alone or distant relapses including the spine) within 2 years of enrollment in patients treated with WVSCI. The final analysis will include an exact binomial confidence interval of spinal failure rate.
Failure rate	Within 2 years of enrollment	Will be measured by the number of progressions or deaths within 2 years of enrollment for the cohort treated with whole ventricular + spinal canal irradiation (WVSCI). The final analysis will include an exact binomial confidence interval of the failure rate for each of the failure types (local, distant/spinal or both) without adjustment for multiplicity.

Secondary Outcome Measures

Name	Time	Method
Radiographic complete response (CR)/partial response (PR) with marker normalization rate post induction/second-look surgery	Approximately 6 to 9 months post-treatment initiation	Will be assessed in patients treated with induction chemotherapy. Will be estimated using an exact binomial approach and its confidence interval.
Patterns of disease recurrence/failure	Up to 10 years	Will be analyzed in an exploratory manner with respect to radiation dose distribution.
Overall survival (OS)	From enrollment until death from any cause for patients with events and until final follow up for those who are alive at the time of analysis, assessed up to 10 years	Will be estimated separately for those treated with WVSCI and with HDCSCR + radiation therapy. Kaplan-Maier based OS curve estimates will be included, where patients who are lost to follow up will be treated as censored observations as part of the secondary analyses.
Radiographic complete response (CR)/partial response (PR) with marker normalization rate post high-dose chemotherapy with peripheral stem cell rescue (HDCSCR)	Up to 2 years post-treatment initiation	Will be assessed in patients treated with HDCSCR. Will be estimated using an exact binomial approach and its confidence interval.
Progression-free survival (PFS)	From enrollment until disease progression or death from any cause for patients with events, and until final follow up for those who are event free at the time of analysis, assessed up to 10 years	Will be estimated separately for those treated with WVSCI and with HDCSCR + radiation therapy. Kaplan-Maier based PFS curve estimates will be included, where patients who are lost to follow up will be treated as censored observations as part of the primary analyses.

Trial Locations

Locations (154)

University of Kentucky/Markey Cancer Center; 🇺🇸 Lexington, Kentucky, United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center; 🇺🇸 Lebanon, New Hampshire, United States

Sydney Children's Hospital; 🇦🇺 Randwick, New South Wales, Australia

IWK Health Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Children's Hospital of Alabama; 🇺🇸 Birmingham, Alabama, United States

Providence Alaska Medical Center; 🇺🇸 Anchorage, Alaska, United States

Banner Children's at Desert; 🇺🇸 Mesa, Arizona, United States

Phoenix Childrens Hospital; 🇺🇸 Phoenix, Arizona, United States

Banner University Medical Center - Tucson; 🇺🇸 Tucson, Arizona, United States

University of Arizona Cancer Center-North Campus; 🇺🇸 Tucson, Arizona, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Kaiser Permanente Downey Medical Center; 🇺🇸 Downey, California, 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

Kaiser Permanente Los Angeles Medical Center; 🇺🇸 Los Angeles, California, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Valley Children's Hospital; 🇺🇸 Madera, 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

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

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

Arnold Palmer Hospital for Children; 🇺🇸 Orlando, Florida, United States

Nemours Children's Hospital; 🇺🇸 Orlando, 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

Loyola University Medical Center; 🇺🇸 Maywood, 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

Norton Children's Hospital; 🇺🇸 Louisville, Kentucky, United States

Ochsner Medical Center Jefferson; 🇺🇸 New Orleans, Louisiana, United States

Eastern Maine Medical Center; 🇺🇸 Bangor, Maine, United States

Maine Children's Cancer Program; 🇺🇸 Scarborough, Maine, United States

Sinai Hospital of Baltimore; 🇺🇸 Baltimore, Maryland, United States

Johns Hopkins University/Sidney Kimmel Cancer Center; 🇺🇸 Baltimore, 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

Michigan State University Clinical Center; 🇺🇸 East Lansing, Michigan, United States

Corewell Health Grand Rapids Hospitals - Butterworth Hospital; 🇺🇸 Grand Rapids, 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

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

University of Missouri Children's Hospital; 🇺🇸 Columbia, Missouri, 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

GenesisCare USA - Las Vegas; 🇺🇸 Las Vegas, Nevada, United States

Alliance for Childhood Diseases/Cure 4 the Kids Foundation; 🇺🇸 Las Vegas, Nevada, United States

Renown Regional Medical Center; 🇺🇸 Reno, Nevada, United States

Cancer Care Specialists - Reno; 🇺🇸 Reno, Nevada, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States

Saint Peter's University Hospital; 🇺🇸 New Brunswick, New Jersey, United States

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital; 🇺🇸 New Brunswick, 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-Einstein Campus; 🇺🇸 Bronx, New York, United States

Montefiore Medical Center - Moses Campus; 🇺🇸 Bronx, New York, United States

Maimonides Medical Center; 🇺🇸 Brooklyn, 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

Stony Brook University Medical Center; 🇺🇸 Stony Brook, 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

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

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Dayton Children's Hospital; 🇺🇸 Dayton, Ohio, United States

ProMedica Flower Hospital; 🇺🇸 Sylvania, 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

Lehigh Valley Hospital-Cedar Crest; 🇺🇸 Allentown, Pennsylvania, United States

Geisinger Medical Center; 🇺🇸 Danville, Pennsylvania, United States

Penn State Children's Hospital; 🇺🇸 Hershey, 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

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

Prisma Health Cancer Institute - Faris; 🇺🇸 Greenville, South Carolina, United States

Sanford USD Medical Center - Sioux Falls; 🇺🇸 Sioux Falls, South Dakota, United States

Saint Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States

The Children's Hospital at TriStar Centennial; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt University/Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Dell Children's Medical Center of Central Texas; 🇺🇸 Austin, Texas, United States

Driscoll Children's Hospital; 🇺🇸 Corpus Christi, 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

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

University of Virginia Cancer Center; 🇺🇸 Charlottesville, Virginia, 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

Marshfield Medical Center-Marshfield; 🇺🇸 Marshfield, Wisconsin, United States

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

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada

CancerCare Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

The Montreal Children's Hospital of the MUHC; 🇨🇦 Montreal, Quebec, Canada

Centre Hospitalier Universitaire Sainte-Justine; 🇨🇦 Montreal, Quebec, Canada

CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL); 🇨🇦 Quebec, Canada

Christchurch Hospital; 🇳🇿 Christchurch, New Zealand