Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia

Phase 2

Completed

Conditions: Hepatoblastoma
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recurrent Osteosarcoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Malignant Germ Cell Tumor
Recurrent Childhood Rhabdomyosarcoma
Previously Treated Childhood Rhabdomyosarcoma
Recurrent Childhood Kidney Neoplasm
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Soft Tissue Sarcoma

Interventions: Drug: Alisertib
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study

Registration Number: NCT01154816

Lead Sponsor: Children's Oncology Group

Brief Summary: This phase II trial is studying the side effects of and how well alisertib works in treating young patients with relapsed or refractory solid tumors or leukemia. Alisertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description: PRIMARY OBJECTIVE:

I. To determine the objective response rate to MLN8237 (alisertib) in children with relapsed or refractory solid tumors and leukemias, administered once daily for 7 days every 21 days.

SECONDARY OBJECTIVES:

I. To further define and describe the toxicities of MLN8237 administered on this schedule.

II. To further characterize the pharmacokinetics of MLN8237 in children with refractory cancer.

III. To evaluate aurora A kinase expression using immunohistochemistry in solid tumors and leukemic blasts from tissue obtained at diagnosis and, if available, at relapse.

IV. To explore the relationship between polymorphic variations in the UDP-glucuronosyltransferase gene UGT1A1 and exposure to MLN8237, and to assess 2 common polymorphic variants in the aurora A kinase gene, Phe31Ile and Val57Ile.

OUTLINE: This is a multicenter study. Patients are stratified according to type of tumor (measurable neuroblastoma vs neuroblastoma with metaiodobenzylguanidine \[MIBG\]-positive lesions vs osteosarcoma vs Ewing sarcoma/primitive neuroectodermal tumor \[PNET\] vs rhabdosarcoma vs non-rhabdomyosarcoma \[RMS\] soft tissue sarcoma vs hepatoblastoma vs malignant germ cell tumor vs Wilms tumor vs acute myeloid leukemia \[AML\] vs acute lymphoblastic leukemia \[ALL\] vs rhabdoid tumors).

ARM I (NEUROBLASTOMA- MEASURABLE): Patients receive alisertib orally (PO) once daily (QD) on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM II (NEUROBLASTOMA-MIBG EVALUABLE): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM III (RHABDOMYOSARCOMA): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM IV (OSTEOSARCOMA): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM V (EWING SARCOMA/ PERIPHERAL PNET): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM VI (NON-RMS SOFT TISSUE SARCOMA): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM VII (HEPATOBLASTOMA): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM VIII (MALIGNANT GERM CELL TUMOR): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM IX (WILMS TUMOR): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM X (ACUTE LYMPHOBLASTIC LEUKEMIA): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM XI (ACUTE MYELOGENOUS LEUKEMIA): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

ARM XII (RHABDOID MALIGNANCY): Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

Plasma samples are collected from all patients at baseline and periodically during course 1 for pharmacokinetic and other studies.

After completion of study therapy, patients are followed up for 5 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 118

Inclusion Criteria

Patients must have had histologic verification of malignancy at original diagnosis or at relapse, to include any of the following malignancies (no other histology is eligible):
- Neuroblastoma- measurable
- Neuroblastoma- MIBG evaluable
- Rhabdomyosarcoma
- Osteosarcoma
- Ewing sarcoma/Peripheral PNET
- Non-RMS soft tissue sarcoma
- Hepatoblastoma
- Malignant germ cell tumor
- Wilms tumor
- Acute lymphoblastic leukemia
- Acute myelogenous leukemia
- Rhabdoid malignancy
Disease status for solid tumor patients:
- Patients must have radiographically measurable disease (with the exception of neuroblastoma)
- Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 20 mm in at least one dimension; for spiral CT, measurable disease is defined as a minimum diameter of 10 mm in at least one dimension
- Note: The following do not qualify as measurable disease:
  - Malignant fluid collections (e.g., ascites, pleural effusions)
  - Bone marrow infiltration
  - Lesions detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans)
  - Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
  - Previously irradiated lesions that have not demonstrated clear progression post radiation
- Patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable disease are eligible
Disease status for leukemia patients:
- Patients with leukemia must be recurrent or refractory to at least two prior induction or treatment regimens, in addition to the following criteria:
- Acute lymphoid leukemia:
  - 25% blasts in the bone marrow (M3 bone marrow), excluding patients with known central nervous system (CNS) disease
- Acute myeloid leukemia according to FAB classification
  - ≥ 5 % blasts in the bone marrow (M2/M3 bone marrow); excluding patients with known CNS disease
Rhabdoid tumors:
- To be eligible for enrollment in the rhabdoid tumors stratum, the patient must have a solid tumor where the institutional pathological evaluation of the tumor at initial diagnosis or relapse has confirmed:
  - Morphology and immunophenotypic panel consistent with rhabdoid tumor (required)
  - Loss of SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1 (INI1) confirmed by immunohistochemistry, or
  - Molecular confirmation of tumor-specific bi-allelic INI1 loss/mutation if INI1 immunohistochemistry is not available; note that molecular confirmation of tumor-specific bi-allelic INI1 loss/mutation is encouraged in cases where INI1 immunohistochemistry is equivocal
Patients must have a Lansky or Karnofsky performance status score of ≥ 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age; Note: 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
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
Myelosuppressive chemotherapy:
- Solid tumors:
  - Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
- Leukemia:
  - Patients with leukemia who relapse while receiving standard maintenance therapy will not be required to have a waiting period before enrollment onto this study
  - Patients who relapse while they are not receiving standard maintenance therapy must have completely recovered from all acute toxic effects of chemotherapy, immunotherapy or radiotherapy prior to study enrollment; at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea
  - Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of MLN8237
At least 7 days must have elapsed since the completion of therapy with a growth factor; at least 14 days must have elapsed after receiving pegfilgrastim
At least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
≥ 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); ≥ 6 weeks must have elapsed since treatment with therapeutic doses of MIBG; ≥ 6 months must have elapsed if prior craniospinal XRT was received, if ≥ 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; ≥ 6 weeks must have elapsed if other substantial bone marrow irradiation was given
No evidence of active graft vs. host disease and ≥ 3 months must have elapsed since transplant
For patients with solid tumors without bone marrow involvement:
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
- Hemoglobin > 8.0 g/dL (may receive red blood cell [RBC] transfusions)
For patients with solid tumors and known bone marrow metastatic disease:
- Peripheral absolute neutrophil count (ANC) ≥ 750/mm^3
- Platelet count ≥ 50,000/mm^3
- Hemoglobin ≥ 8.0 g/dL
- Transfusions are permitted to meet both the platelet and hemoglobin criteria; patients must not be known to be refractory to red blood cell or platelet transfusions
Patients with leukemia must not be known to be refractory to red blood cell or platelet transfusions
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:
- 1 to < 2 years: 0.6
- 2 to < 6 years: 0.8
- 6 to < 10 years: 1
- 10 to < 13 years: 1.2
- 13 to < 16 years: 1.5 (male), 1.4 (female)
- >= 16 years: 1.7 (male), 1.4 (female)
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
Serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 5.0 x ULN for age (≤ 225 U/L); for the purpose of this study, the ULN for SGPT is 45 U/L
Serum albumin ≥ 2 g/dL
All patients and/or their parents or legal guardians must sign a written informed consent

Exclusion Criteria

Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; breastfeeding women are excluded
Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim)
Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible
Patients who are currently receiving another investigational drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Use of daily benzodiazepine therapy excludes a patient from being eligible because of the potential benzodiazepine-like effects of MLN8237
Patients who are currently receiving digoxin, cyclosporine, tacrolimus, or sirolimus are not eligible
Patients who are unable to swallow tablets are not eligible
Patients who have an uncontrolled infection are not eligible
Leukemia patients with CNS disease are not eligible
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm VI (non-RMS soft tissue sarcoma)	Alisertib	Patients with non-RMS soft tissue sarcoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm VII (hepatoblastoma)	Alisertib	Patients hepatoblastoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm VIII (malignant germ cell tumor)	Alisertib	Patients with malignant germ cell tumor receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm XI (acute myelogenous leukemia)	Alisertib	Patients acute myelogenous leukemia receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm II (Neuroblastoma- MIBG evaluable)	Pharmacological Study	Patients MIBG evaluable neuroblastoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm IV (osteosarcoma)	Pharmacological Study	Patients with osteosarcoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm VII (hepatoblastoma)	Laboratory Biomarker Analysis	Patients hepatoblastoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm VIII (malignant germ cell tumor)	Pharmacological Study	Patients with malignant germ cell tumor receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm VIII (malignant germ cell tumor)	Laboratory Biomarker Analysis	Patients with malignant germ cell tumor receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm I (neuroblastoma- measurable)	Laboratory Biomarker Analysis	Patients with measurable neuroblastoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm I (neuroblastoma- measurable)	Pharmacological Study	Patients with measurable neuroblastoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm III (rhabdomyosarcoma)	Laboratory Biomarker Analysis	Patients with rhabdomyosarcoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm III (rhabdomyosarcoma)	Pharmacological Study	Patients with rhabdomyosarcoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm V (Ewing sarcoma/peripheral PNET)	Pharmacological Study	Patients with Ewing sarcoma/peripheral PNET receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm VI (non-RMS soft tissue sarcoma)	Pharmacological Study	Patients with non-RMS soft tissue sarcoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm II (Neuroblastoma- MIBG evaluable)	Laboratory Biomarker Analysis	Patients MIBG evaluable neuroblastoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm IV (osteosarcoma)	Laboratory Biomarker Analysis	Patients with osteosarcoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm VI (non-RMS soft tissue sarcoma)	Laboratory Biomarker Analysis	Patients with non-RMS soft tissue sarcoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm V (Ewing sarcoma/peripheral PNET)	Laboratory Biomarker Analysis	Patients with Ewing sarcoma/peripheral PNET receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm VII (hepatoblastoma)	Pharmacological Study	Patients hepatoblastoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm IX (Wilms tumor)	Laboratory Biomarker Analysis	Patients with Wilms tumor receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm X (acute lymphoblastic leukemia)	Pharmacological Study	Patients with acute lymphoblastic leukemia receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm XII (rhabdoid malignancy)	Pharmacological Study	Patients with rhabdoid malignancy receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm IX (Wilms tumor)	Pharmacological Study	Patients with Wilms tumor receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm IX (Wilms tumor)	Alisertib	Patients with Wilms tumor receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm X (acute lymphoblastic leukemia)	Laboratory Biomarker Analysis	Patients with acute lymphoblastic leukemia receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm XI (acute myelogenous leukemia)	Laboratory Biomarker Analysis	Patients acute myelogenous leukemia receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm XI (acute myelogenous leukemia)	Pharmacological Study	Patients acute myelogenous leukemia receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm XII (rhabdoid malignancy)	Laboratory Biomarker Analysis	Patients with rhabdoid malignancy receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm II (Neuroblastoma- MIBG evaluable)	Alisertib	Patients MIBG evaluable neuroblastoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm I (neuroblastoma- measurable)	Alisertib	Patients with measurable neuroblastoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm III (rhabdomyosarcoma)	Alisertib	Patients with rhabdomyosarcoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm IV (osteosarcoma)	Alisertib	Patients with osteosarcoma receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm V (Ewing sarcoma/peripheral PNET)	Alisertib	Patients with Ewing sarcoma/peripheral PNET receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm X (acute lymphoblastic leukemia)	Alisertib	Patients with acute lymphoblastic leukemia receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Arm XII (rhabdoid malignancy)	Alisertib	Patients with rhabdoid malignancy receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Overall Response	From first dose of alisertib through 6 cycles of protocol therapy or until removal from protocol therapy whichever occurred first.	For patients with recurrent solid tumors a patient who experienced a complete or partial response according to RECIST version 1.1 criteria is considered a responder. For patients with recurrent acute lymphoblastic leukemia a patient who experiences a bone marrow evaluation with \< 5% blast cells on morphological evaluation of bone marrow will be considered a responder. For patients with recurrent acute myelogenous leukemia a patient who experiences a complete remission or complete remission with partial recovery of platelet count according to the AML International Working Group Criteria will be considered a responder.

Secondary Outcome Measures

Name	Time	Method
Number of Patients Cycles With Grade 3 or Higher Adverse Event	Up to 24 months	The number of patient-cycles in which the adverse event considered grade 3 or higher AE according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 considered by the treating physician to be possibly, probably or definitely related to alisertib.
Serum Concentration of Alisertib on the First Day of Administration Six Hours After Administration	day 1 of protocol therapy	Serum concentration of alisertib on the first day of administration six hours after administration in nanograms/milliliter.
Serum Concentration of Alisertib on the Fourth Day of Administration Prior to the Administration of the Day 4 Dose	day 4 of protocol therapy	Serum concentration of alisertib on the fourth day of administration prior to the administration of the day 4 dose in nanograms/milliliter.
Serum Concentration of Alisertib on the First Day of Administration One Hour After Administration	day 1 of protocol therapy	Serum concentration of alisertib on the first day of administration one hour after administration in nanograms/milliliter.
Serum Concentration of Alisertib on the Seventh Day of Administration Prior to the Administration of the Day 7 Dose.	day 7 of protocol therapy	Serum concentration of alisertib on the seventh day of administration prior to the administration of the day 7 dose in nanograms/milliliter.
Serum Concentration of Alisertib Prior to the First Day of Administration	day 1 of protocol therapy	Serum concentration of alisertib prior to the first day of administration in nanograms/milliliter.
Serum Concentration of Alisertib on the First Day of Administration Three Hours After Administration	day 1 of protocol therapy	Serum concentration of alisertib on the first day of administration three hours after administration in nanograms/milliliter.

Trial Locations

Locations (105): Nemours Children's Clinic-Jacksonville
🇺🇸
Jacksonville, Florida, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸
Long Beach, California, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Southern California Permanente Medical Group
🇺🇸
Downey, California, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
St. Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
Alberta Children's Hospital
🇨🇦
Calgary, Alberta, Canada
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸
Houston, Texas, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Children's Hospital Central California
🇺🇸
Madera, California, United States
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸
Palo Alto, California, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
University of Illinois
🇺🇸
Chicago, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸
Springfield, Illinois, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸
Iowa City, Iowa, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Columbia University/Herbert Irving Cancer Center
🇺🇸
New York, New York, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Mercy Children's Hospital
🇺🇸
Toledo, Ohio, United States
Natalie Warren Bryant Cancer Center at Saint Francis
🇺🇸
Tulsa, Oklahoma, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Childrens Oncology Group
🇺🇸
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
Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
Medical City Dallas Hospital
🇺🇸
Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸
Dallas, Texas, United States
Childrens Hospital-King's Daughters
🇺🇸
Norfolk, Virginia, United States
Carilion Clinic Children's Hospital
🇺🇸
Roanoke, Virginia, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Mercy Hospital Saint Louis
🇺🇸
Saint Louis, Missouri, United States
Winthrop University Hospital
🇺🇸
Mineola, New York, United States
New York Medical College
🇺🇸
Valhalla, New York, United States
Penn State Hershey Children's Hospital
🇺🇸
Hershey, Pennsylvania, United States
East Tennessee Childrens Hospital
🇺🇸
Knoxville, Tennessee, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸
Spokane, Washington, United States
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, 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 Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Legacy Emanuel Children's Hospital
🇺🇸
Portland, Oregon, United States
Legacy Emanuel Hospital and Health Center
🇺🇸
Portland, Oregon, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Methodist Children's Hospital of South Texas
🇺🇸
San Antonio, Texas, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸
Pensacola, Florida, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Lee Memorial Health System
🇺🇸
Fort Myers, Florida, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Overlook Hospital
🇺🇸
Summit, New Jersey, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
British Columbia Children's Hospital
🇨🇦
Vancouver, British Columbia, Canada
Sinai Hospital of Baltimore
🇺🇸
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Dayton Children's Hospital
🇺🇸
Dayton, Ohio, United States
Saint Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
Palmetto Health Richland
🇺🇸
Columbia, South Carolina, United States
University of Vermont College of Medicine
🇺🇸
Burlington, Vermont, United States
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
IWK Health Centre
🇨🇦
Halifax, Nova Scotia, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦
Kingston, Ontario, Canada
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸
Tampa, Florida, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Children's Hospital and Medical Center of Omaha
🇺🇸
Omaha, Nebraska, United States
Children¿s Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
University of Hawaii Cancer Center
🇺🇸
Honolulu, Hawaii, United States
Nemours Children's Clinic - Orlando
🇺🇸
Orlando, Florida, United States
UF Cancer Center at Orlando Health
🇺🇸
Orlando, Florida, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Florida Hospital Orlando
🇺🇸
Orlando, Florida, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
The Childrens Mercy Hospital
🇺🇸
Kansas City, Missouri, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States