Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma
- Conditions
- Anaplastic Large Cell Lymphoma, ALK-PositiveAnn Arbor Stage III Noncutaneous Childhood Anaplastic Large Cell LymphomaAnn Arbor Stage II Noncutaneous Childhood Anaplastic Large Cell LymphomaAnn Arbor Stage IV Noncutaneous Childhood Anaplastic Large Cell Lymphoma
- Interventions
- Registration Number
- NCT01979536
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This partially randomized phase II trial studies how well brentuximab vedotin or crizotinib and combination chemotherapy works in treating patients with newly diagnosed stage II-IV anaplastic large cell lymphoma. Brentuximab vedotin is a monoclonal antibody, called brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in targeted way and delivers vedotin to kill them. Crizotinib and methotrexate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether brentuximab vedotin and combination chemotherapy is more effective than crizotinib and combination chemotherapy in treating anaplastic large cell lymphoma.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine the tolerability of brentuximab vedotin given in combination with standard chemotherapy (anaplastic large cell lymphoma \[ALCL\]99) and to determine the tolerability of crizotinib given in combination with chemotherapy (ALCL99).
II. To estimate the event free survival (EFS) of Arm brentuximab vedotin (BV) and Arm crizotinib (CZ) and contrast these to historical control data.
SECONDARY OBJECTIVES:
I. To determine the prognostic significance of minimal disseminated disease (MDD) at diagnosis and minimal residual disease (MRD) as measured by real-time (RT)-polymerase chain reaction (PCR) in peripheral blood.
OUTLINE: Patients with body surface area (BSA) \< 0.9 m\^2 were non-randomly assigned to Arm BV while it was open and were not eligible for the trial while Arm BV was closed. Patients with BSA \>= 0.9 m\^2 were randomly assigned 1:1 to Arm BV or Arm CZ while both were open and were non-randomly assigned to the open arm while only one of the two arms was open.
ARM BV:
COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin (1.8 mg/dg/dose - Max dose 180 mg) intravenously (IV) over 30 minutes on day 1, dexamethasone orally (PO) twice daily (BID) or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5.
COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin (1.8 mg/dg/dose - Max dose 180 mg), dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5.
ARM CZ:
COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib (165 mg/m\^2) PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A.
COURSE B (CYCLES 2, 4, AND 6): Patients receive crizotinib (165 mg/m\^2) PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B.
In all arms, treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 137
- Newly diagnosed patients with histologically proven ALCL (International Classification of Diseases for Oncology [ICD-0] code: 9714/3)
- Disease must be cluster of differentiation (CD)30 positive
- Disease must be anaplastic lymphoma kinase (ALK) positive (defined by local institutional standards)
- Patients must have stage II, III, or IV disease
- Patients must have a life expectancy of >= 8 weeks
- Adequate Liver Function Defined As:
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for ALT is 45 U/L (within 7 days prior to enrollment)
- If the lab abnormality is thought to be due to the lymphoma the patient is eligible and dose adjustments should be made
- Adequate Cardiac Function Defined As:
- Shortening fraction of >= 27% by echocardiogram, or
- Ejection fraction of >= 50% by radionuclide angiogram
- Adequate Pulmonary Function Defined As:
- Patients with a history of pulmonary dysfunction must have no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry > 92% while breathing room air unless current dysfunction is due to the lymphoma in which case the patient is eligible
- Patients with central nervous system (CNS) disease are not eligible
- Patients with disease limited to the skin are not eligible, regardless of how wide-spread
- Patients with stage I disease are not eligible
- Patients who have received any prior cytotoxic chemotherapy for the current diagnosis of ALCL or any cancer diagnosed previously are not eligible
- Previous steroid treatment and/or radiation treatment is not allowed unless it is for the emergent management of a mediastinal mass; emergent steroid treatment and/or radiation treatment should stop once protocol therapy is initiated
- Intrathecal chemotherapy prior to enrollment is allowed for the current diagnosis of ALCL as long as adequate cerebrospinal fluid (CSF) is obtained prior to administration of the intrathecal chemotherapy and subsequently demonstrated to be negative for ALCL
- Female patients who are pregnant are not eligible; pregnancy tests must be obtained in girls who are post menarchal
- Lactating females are not eligible unless they have agreed not to breastfeed their infants
- Sexually active patients of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of treatment and for 3 months after stopping treatment
- Patients with Down syndrome are not eligible due to the amount of methotrexate and potential for side effects
- Patients with an immunodeficiency that existed prior to diagnosis such as primary immunodeficiency syndromes or organ transplant recipients are not eligible
- Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates with narrow therapeutic indices: Patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use of these medications (if applicable) is allowed
- CYP3A4 inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed
- CYP3A4 inducers: patients chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, ritonavir, and St. John's wort are not eligible; the topical use of these medications (if applicable) is allowed
- Patients that are known to be positive for human immunodeficiency virus (HIV) are not eligible; note: inclusion of HIV positive patients will be considered at a later date
- Patients who weigh < 10 kg are not eligible
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm CZ (crizotinib, combination chemotherapy) Crizotinib COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A. COURSE B (CYCLES 2, 4, AND 6): Patients receive crizotinib PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B. Arm BV (brentuximab vedotin, combination chemotherapy) Brentuximab Vedotin COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO BID or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5. COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5. Arm BV (brentuximab vedotin, combination chemotherapy) Cyclophosphamide COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO BID or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5. COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5. Arm BV (brentuximab vedotin, combination chemotherapy) Dexamethasone COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO BID or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5. COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5. Arm BV (brentuximab vedotin, combination chemotherapy) Cytarabine COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO BID or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5. COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5. Arm BV (brentuximab vedotin, combination chemotherapy) Doxorubicin Hydrochloride COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO BID or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5. COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5. Arm BV (brentuximab vedotin, combination chemotherapy) Methotrexate COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO BID or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5. COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5. Arm BV (brentuximab vedotin, combination chemotherapy) Etoposide COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO BID or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5. COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5. Arm BV (brentuximab vedotin, combination chemotherapy) Ifosfamide COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO BID or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5. COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5. Arm CZ (crizotinib, combination chemotherapy) Cyclophosphamide COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A. COURSE B (CYCLES 2, 4, AND 6): Patients receive crizotinib PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B. Arm CZ (crizotinib, combination chemotherapy) Dexamethasone COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A. COURSE B (CYCLES 2, 4, AND 6): Patients receive crizotinib PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B. Arm CZ (crizotinib, combination chemotherapy) Cytarabine COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A. COURSE B (CYCLES 2, 4, AND 6): Patients receive crizotinib PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B. Arm CZ (crizotinib, combination chemotherapy) Doxorubicin Hydrochloride COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A. COURSE B (CYCLES 2, 4, AND 6): Patients receive crizotinib PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B. Arm CZ (crizotinib, combination chemotherapy) Etoposide COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A. COURSE B (CYCLES 2, 4, AND 6): Patients receive crizotinib PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B. Arm CZ (crizotinib, combination chemotherapy) Ifosfamide COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A. COURSE B (CYCLES 2, 4, AND 6): Patients receive crizotinib PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B. Arm CZ (crizotinib, combination chemotherapy) Methotrexate COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A. COURSE B (CYCLES 2, 4, AND 6): Patients receive crizotinib PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B.
- Primary Outcome Measures
Name Time Method Event Free Survival (EFS) Time from study entry until progressive disease, relapse, or death, assessed up to 2 years The Kaplan-Meier method will be used to estimate the 2-year EFS for each of the treatment regimens.
Occurrence of Grade 3+ Non-hematologic Adverse Events Up to 60 months Will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicities will be summarized by individual toxicity counts separated by arm.
- Secondary Outcome Measures
Name Time Method Prognostic Significance of Minimal Residual Disease Baseline up to progressive disease, relapse, or death, assessed up to 2 years Analyzed by estimating the 2-year EFS of negative MRD and positive MRD by arm. Minimal disease was performed using serial assessments of the t(2;5)(p23;q35) NPM-ALK fusion transcript using quantitative RT-PCR. Quantitative RT-PCR was performed by extracting total RNA from peripheral blood specimens. Peripheral blood samples were obtained at baseline, on day 1 of cycle 1, and on day 1 of cycle 2. The normalized copy numbers (NCN) were expressed as copy numbers of NPM-ALK per 104 copies of ABL. Minimal disease (MDD) was defined as \>10 NCN at baseline.
Trial Locations
- Locations (154)
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
Naval Medical Center - Portsmouth
🇺🇸Portsmouth, Virginia, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Ascension Saint Vincent Indianapolis Hospital
🇺🇸Indianapolis, Indiana, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Children's Hospital of San Antonio
🇺🇸San Antonio, Texas, United States
UCSF Medical Center-Parnassus
🇺🇸San Francisco, California, United States
The Children's Hospital at TriStar Centennial
🇺🇸Nashville, Tennessee, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Naval Medical Center -San Diego
🇺🇸San Diego, California, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Columbia Regional
🇺🇸Columbia, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, 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
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Ascension Saint John Hospital
🇺🇸Detroit, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Mission Hospital
🇺🇸Asheville, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Saint Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
Prisma Health Richland Hospital
🇺🇸Columbia, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
T C Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Saint Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, 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
Mary Bridge Children's Hospital and Health Center
🇺🇸Tacoma, Washington, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸Oak Lawn, Illinois, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
Arnold Palmer Hospital for Children
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Michigan State University Clinical Center
🇺🇸East Lansing, Michigan, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, 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
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸Toledo, Ohio, United States
Legacy Emanuel Children's Hospital
🇺🇸Portland, Oregon, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
El Paso Children's Hospital
🇺🇸El Paso, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Beaumont Children's Hospital-Royal Oak
🇺🇸Royal Oak, Michigan, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
NYU Winthrop Hospital
🇺🇸Mineola, New York, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States