Treatment With Dinutuximab, Sargramostim (GM-CSF), and Isotretinoin in Combination With Irinotecan and Temozolomide After Intensive Therapy for People With High-Risk Neuroblastoma (NBL)

Registration Number
NCT04385277
Lead Sponsor
Children's Oncology Group
Brief Summary

This phase II trial studies if dinutuximab, GM-CSF, isotretinoin in combination with irinotecan, and temozolomide (chemo-immunotherapy) can be given safely to patients with high-risk neuroblastoma after Consolidation therapy (which usually consists of two autologous stem cell transplants and radiation) who have not experienced worsening or recurrence of thei...

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the feasibility of administering dinutuximab, GM-CSF, and isotretinoin in combination with irinotecan and temozolomide in the frontline Post-Consolidation setting in patients with high-risk neuroblastoma who have undergone Induction and Consolidation therapy with tandem high-dose chemotherapy with stem cell rescue (ASCT)....

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
41
Inclusion Criteria

  • Patients must be < 31 years of age at the time of enrollment.

  • Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) (verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites at the time of diagnosis) and have been designated as having high-risk disease based on Children's Oncology Group (COG) risk classification. The following disease groups are eligible:

    • Patients with International Neuroblastoma Risk Group (INRG) Stage M disease with any of the following features:

      • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
      • Age > 547 days at the time of diagnosis regardless of biologic features; OR
      • Age 365-547 days at the time of diagnosis with tumors with unfavorable histology and/or deoxyribonucleic acid (DNA) index = 1

    • Patients with INRG Stage MS disease with MYCN amplification

    • Patients with INRG Stage L2 disease with either of the following features:

      • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
      • Age > 547 days at the time of diagnosis with MYCN non-amplified tumors with unfavorable histology

    • Note: Patients observed or patients treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet criteria will also be eligible

  • 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

  • Prior therapy

    • All patients must have completed high-risk Induction therapy with 4-6 cycles of chemotherapy
    • After completion of Induction therapy, patients may have received no more than 4 cycles of bridging chemotherapy or chemo-immunotherapy prior to ASCT
    • Patients cannot have previously progressed on immunotherapy with dinutuximab or other anti-GD2 monoclonal antibody
    • All patients must have had undergone surgical resection of their primary tumor as part of frontline therapy. Exceptions to this requirement include patients who had a complete response to Induction chemotherapy, patients with no identifiable primary tumor, and patients for whom the institutional surgical team determined that potential risks outweighed potential benefits of resection
    • All patients must have undergone tandem high-dose chemotherapy with ASCT as part of Consolidation
    • Patients must enroll between day +56 and day +200 from the peripheral blood stem cell (PBSC) infusion following the last dose of high-dose chemotherapy during Consolidation
    • All patients must have undergone external beam radiation therapy. Exceptions to this requirement include patients who had no identifiable primary tumor and no persistent metastatic disease at the end of Induction. For patients who received radiotherapy, at least 7 days must have elapsed between completion of radiotherapy and enrollment on this study

  • Patients must not have received long-acting myeloid growth factors (e.g., Neulasta) within 14 days of entry on this study. Seven days must have elapsed since administration of a short-acting myeloid growth factor

  • Peripheral absolute neutrophil count (ANC) >= 750/uL

  • Platelet count >= 50,000/uL (transfusion independent for >= 7 days)

  • 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:

    • Age: Maximum Serum Creatinine (mg/dL)

    • 6 months to < 1 year: 0.5 (male and female)

    • 1 to < 2 years: 0.6 (male and female)

    • 2 to < 6 years: 0.8 (male and female)

    • 6 to < 10 years: 1 (male and female)

    • 10 to < 13 years: 1.2 (male and female)

    • 13 to < 16 years: 1.5 (male), 1.4 (female)

    • >= 16 years: 1.7 (male), 1.4 (female)

      • Note: Patients with history of transplant associated-thrombotic microangiopathy (TA-TMA) must have a creatinine clearance or radioisotope GFR at baseline to assess renal function and must meet the above criteria

  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5.0 x ULN for age (=< 225 U/L)

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

  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by echocardiogram or radionuclide angiogram

  • Absence of dyspnea at rest

  • If pulmonary function tests (PFTs) are performed, forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) must be > 60%

  • No clinical evidence of active central nervous system (CNS) disease at the time of study enrollment

  • Patients with seizure disorder may be enrolled if on non-enzyme-inducing anticonvulsants and well controlled

  • CNS toxicity from prior therapy =< grade 2

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Exclusion Criteria

  • Patients must not have had progressive disease (PD) per the revised International Neuroblastoma Risk Criteria (INRC) since the initial diagnosis of high-risk neuroblastoma

    • Exception: Progressive disease within the first 2 cycles of Induction chemotherapy consisting of cyclophosphamide and topotecan is allowed. Patients with progression subsequent to initial cyclophosphamide and topotecan cycles are excluded

  • Patients may not have received additional systemic cancer-directed therapy following completion of the last planned high-dose chemotherapy with ASCT prior to enrollment on this trial

  • Patients may not have received iodine-131 (131I)-metaiodobenzylguanidine (MIBG) therapy at any time prior to enrollment on this trial

  • Patients who received single (rather than tandem) high-dose chemotherapy with ASCT are excluded

  • Patients cannot be receiving other ongoing anticancer therapy

  • Patients who were enrolled onto ANBL1531 AND underwent arm assignment are not eligible. Patients who enrolled onto ANBL1531 who declined second consent may be eligible for ANBL19P1 if all other criteria are met

  • Patients enrolled onto ANBL17P1 are not eligible

  • Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment

  • Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible. The only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions

    • Note: The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency

  • Patients on any other immunosuppressive medications (e.g., cyclosporine, tacrolimus) are not eligible. However, prior or planned concomitant treatment with eculizumab is permitted (e.g., treatment of TA-TMA)

  • Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, valproic acid, or carbamazepine for at least 7 days prior to study enrollment

    • Note: Patients receiving non-enzyme inducing anticonvulsants such as gabapentin or levetiracetam are eligible

  • Patients must not have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment

  • Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma

  • Patients with symptoms of congestive heart failure are not eligible

  • Patients with moderate or large pericardial effusions are not eligible

  • Patients must not have >= grade 2 diarrhea

  • Patients must not have uncontrolled infection

  • Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required discontinuation of the anti-GD2 therapy are not eligible

  • Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible

  • Female patients who are pregnant 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

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

  • 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

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (temozolomide, irinotecan, dinutuximab)Biospecimen CollectionPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)Bone Marrow AspirationPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)Bone Marrow BiopsyPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)Computed TomographyPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)FDG-Positron Emission TomographyPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)Iobenguane I-123Patients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)Magnetic Resonance ImagingPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)Multigated Acquisition ScanPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)SargramostimPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)IrinotecanPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)IsotretinoinPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)TemozolomidePatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Treatment (temozolomide, irinotecan, dinutuximab)DinutuximabPatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Percentage of Patients Who Complete 5 Cycles of Dinutuximab + Chemotherapy Without Progressive Disease (PD)Within 30 weeks from the date of first treatment

Will be assessed by estimation of the feasibility therapy completion rate together with a 95% Wilson confidence interval (CI).

Secondary Outcome Measures
NameTimeMethod
Event-free Survival (EFS)From the time of start of protocol therapy to the occurrence of disease relapse or progression, secondary malignancy, or death, assessed at 1 year.

EFS Kaplan-Meier estimates will be generated.

Overall Survival (OS)From the time of start of protocol therapy to death, assessed at 1 year.

OS Kaplan-Meier estimates will be generated.

Trial Locations

Locations (77)

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

🇺🇸

Houston, Texas, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

University of Chicago Comprehensive Cancer Center

🇺🇸

Chicago, Illinois, United States

Albany Medical Center

🇺🇸

Albany, New York, United States

Banner Children's at Desert

🇺🇸

Mesa, Arizona, United States

University of Illinois

🇺🇸

Chicago, Illinois, United States

University of Mississippi Medical Center

🇺🇸

Jackson, Mississippi, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Medical City Dallas Hospital

🇺🇸

Dallas, Texas, United States

Morristown Medical Center

🇺🇸

Morristown, New Jersey, United States

Queensland Children's Hospital

🇦🇺

South Brisbane, Queensland, Australia

Children's Healthcare of Atlanta - Egleston

🇺🇸

Atlanta, Georgia, United States

Saint Luke's Cancer Institute - Boise

🇺🇸

Boise, Idaho, United States

UT Southwestern/Simmons Cancer Center-Dallas

🇺🇸

Dallas, Texas, United States

Starship Children's Hospital

🇳🇿

Grafton, Auckland, New Zealand

Saint Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

Sanford Broadway Medical Center

🇺🇸

Fargo, North Dakota, United States

Kaiser Permanente Downey Medical Center

🇺🇸

Downey, California, United States

Golisano Children's Hospital of Southwest Florida

🇺🇸

Fort Myers, Florida, United States

Children's Hospital of Pittsburgh of UPMC

🇺🇸

Pittsburgh, Pennsylvania, United States

Alfred I duPont Hospital for Children

🇺🇸

Wilmington, Delaware, United States

Saint Jude Midwest Affiliate

🇺🇸

Peoria, Illinois, United States

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

🇺🇸

Hollywood, Florida, United States

Cook Children's Medical Center

🇺🇸

Fort Worth, Texas, United States

Mercy Hospital Saint Louis

🇺🇸

Saint Louis, Missouri, United States

State University of New York Upstate Medical University

🇺🇸

Syracuse, New York, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

🇺🇸

New York, New York, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

NYU Winthrop Hospital

🇺🇸

Mineola, New York, United States

Saint Christopher's Hospital for Children

🇺🇸

Philadelphia, Pennsylvania, United States

Perth Children's Hospital

🇦🇺

Perth, Western Australia, Australia

Children's Hospital Medical Center of Akron

🇺🇸

Akron, Ohio, United States

Christchurch Hospital

🇳🇿

Christchurch, New Zealand

IWK Health Centre

🇨🇦

Halifax, Nova Scotia, Canada

Riley Hospital for Children

🇺🇸

Indianapolis, Indiana, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis

🇺🇸

Minneapolis, Minnesota, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, 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

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Arkansas Children's Hospital

🇺🇸

Little Rock, Arkansas, United States

Children's National Medical Center

🇺🇸

Washington, District of Columbia, United States

UCSF Medical Center-Mission Bay

🇺🇸

San Francisco, California, United States

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

🇺🇸

Denver, Colorado, United States

University of Oklahoma Health Sciences Center

🇺🇸

Oklahoma City, Oklahoma, United States

The Children's Hospital at TriStar Centennial

🇺🇸

Nashville, Tennessee, United States

Vanderbilt University/Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Primary Children's Hospital

🇺🇸

Salt Lake City, Utah, United States

Children's Hospital and Medical Center of Omaha

🇺🇸

Omaha, Nebraska, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

El Paso Children's Hospital

🇺🇸

El Paso, Texas, United States

Children's Hospital Colorado

🇺🇸

Aurora, Colorado, United States

Kaiser Permanente-Oakland

🇺🇸

Oakland, California, United States

Connecticut Children's Medical Center

🇺🇸

Hartford, Connecticut, United States

Nemours Children's Clinic-Jacksonville

🇺🇸

Jacksonville, Florida, United States

Lurie Children's Hospital-Chicago

🇺🇸

Chicago, Illinois, United States

University of Iowa/Holden Comprehensive Cancer Center

🇺🇸

Iowa City, Iowa, United States

Walter Reed National Military Medical Center

🇺🇸

Bethesda, Maryland, United States

Carolinas Medical Center/Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

Rainbow Babies and Childrens Hospital

🇺🇸

Cleveland, Ohio, United States

Covenant Children's Hospital

🇺🇸

Lubbock, Texas, United States

UMC Cancer Center / UMC Health System

🇺🇸

Lubbock, Texas, United States

Children's Hospital of The King's Daughters

🇺🇸

Norfolk, Virginia, United States

The Children's Hospital at Westmead

🇦🇺

Westmead, New South Wales, Australia

Royal Children's Hospital

🇦🇺

Parkville, Victoria, Australia

Children's Mercy Hospitals and Clinics

🇺🇸

Kansas City, Missouri, United States

Norton Children's Hospital

🇺🇸

Louisville, Kentucky, United States

Nemours Children's Hospital

🇺🇸

Orlando, Florida, United States

C S Mott Children's Hospital

🇺🇸

Ann Arbor, Michigan, United States

Ochsner Medical Center Jefferson

🇺🇸

New Orleans, Louisiana, United States

University of Florida Health Science Center - Gainesville

🇺🇸

Gainesville, Florida, United States

Dell Children's Medical Center of Central Texas

🇺🇸

Austin, Texas, United States

Montefiore Medical Center - Moses Campus

🇺🇸

Bronx, New York, United States

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