Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

Phase 1

Completed

Conditions: Diffuse Intrinsic Pontine Glioma
Gliosarcoma
Anaplastic Astrocytoma
Anaplastic Oligoastrocytoma

Interventions: Radiation: 3-Dimensional Conformal Radiation Therapy
Radiation: Intensity-Modulated Radiation Therapy
Other: Laboratory Biomarker Analysis
Drug: Vorinostat

Registration Number: NCT01189266

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase I/II trial studies the side effects and best dose of vorinostat and to see how well it works when given together with radiation therapy followed by maintenance therapy with vorinostat in treating younger patients with newly diagnosed diffuse intrinsic pontine glioma (a brainstem tumor). Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vorinostat together with radiation therapy may kill more tumor cells.

Detailed Description: PRIMARY OBJECTIVES:

l. To estimate the maximum tolerated dose (MTD) or recommend a phase 2 dose of vorinostat given concurrently with radiation in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

II. To define and describe the toxicities of vorinostat given concurrently with radiation in children with newly diagnosed DIPG.

III. To determine, in the context of this phase I/II trial, the anti-tumor activity of combining vorinostat with radiation, followed by maintenance vorinostat for twelve courses, in children with newly diagnosed DIPG, as measured by 12-month event-free survival (EFS) and overall survival (OS).

IV. To determine the toxicities of vorinostat for 12 additional courses after completion of vorinostat and radiation.

SECONDARY OBJECTIVES:

I. To measure non-homologous end-joining (NHEJ) activity in peripheral blood mononuclear cells (PBMCs) before treatment, at 2 weeks after starting vorinostat and radiation, and at the end of radiation.

II. To measure histone deacetylase 2 (HDAC2) levels and assess histone acetylation in PBMCs before treatment, at 2 weeks after starting vorinostat and radiation, and at the end of radiation.

III. To quantify deoxyribonucleic acid (DNA) repair proteins from the NHEJ and homologous recombination repair (HHR) pathways in tumors by either Western analysis or immunohistochemistry, if paraffin-embedded tumor is available.

OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.

Patients receive vorinostat orally (PO) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients undergo 3-dimensional (3D) conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. Patients then receive maintenance therapy comprising vorinostat PO on days 1-28. Treatment repeats every 28 days for up to 12 courses 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: 79

Inclusion Criteria

Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons, are eligible without histologic confirmation; patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or anaplastic mixed glioma; patients with juvenile pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible; patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician
Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Patients must not have received any prior treatment except dexamethasone and/or surgery
Peripheral absolute neutrophil count (ANC) >= 1000/uL
Platelet count >= 100,000/uL (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)
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- 0.8 mg/dL (3 to < 6 years of age)
- 1 mg/dL (6 to < 10 years of age)
- 1.2 mg/dL (10 to < 13 years of age)
- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT (ALT) is 45 U/L
Serum albumin >= 2 g/dL
Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants (with the exception of valproic acid) and seizures are well controlled
Patients must be able to swallow capsules or liquids; patients dependent on nasogastric (NG) tube feeding are not permitted to receive protocol therapy
Enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date

Exclusion Criteria

Pregnant or breast-feeding women will not be entered on this study; 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
Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment
Patients who are currently receiving another investigational drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Patients must not currently be receiving enzyme inducing anticonvulsants
Patients on valproic acid must discontinue valproic acid for at least 2 weeks before starting protocol therapy
Patients receiving coumadin, heparin, low-molecular weight heparin, or any other anti-coagulants are not eligible for study entry
Patients receiving acetylsalicylic acid (ASA) (> 81 mg/day), non-steroidal anti-inflammatory drugs, clopidogrel (Plavix), dipyridamole (Persantine), or any other drug that inhibits platelet function are not eligible for study entry
Patients who have an uncontrolled infection 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 3 Phase II Evaluation Vorinostat 230 mg/m^2	Laboratory Biomarker Analysis	Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2	3-Dimensional Conformal Radiation Therapy	Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2	Intensity-Modulated Radiation Therapy	Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 1 Phase I Vorinostat 180 mg/m^2	Intensity-Modulated Radiation Therapy	Patients in phase I received vorinostat at 180 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 1 Phase I Vorinostat 180 mg/m^2	Laboratory Biomarker Analysis	Patients in phase I received vorinostat at 180 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 2 Phase 1 Vorinostat 230 mg/m^2	3-Dimensional Conformal Radiation Therapy	Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 2 Phase 1 Vorinostat 230 mg/m^2	Intensity-Modulated Radiation Therapy	Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 2 Phase 1 Vorinostat 230 mg/m^2	Laboratory Biomarker Analysis	Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 1 Phase I Vorinostat 180 mg/m^2	3-Dimensional Conformal Radiation Therapy	Patients in phase I received vorinostat at 180 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 1 Phase I Vorinostat 180 mg/m^2	Vorinostat	Patients in phase I received vorinostat at 180 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 2 Phase 1 Vorinostat 230 mg/m^2	Vorinostat	Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2	Vorinostat	Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of Vorinostat	Planned 7 weeks during chemoradiotherapy	The dose of vorinostat in mg/sqm/day to be administered with combination chemotherapy and radiation therapy
Event-Free Survival	2 years after study enrollment	Time from enrollment to disease progression, diagnosis of a second malignant neoplasm, death or last follow-up, whichever occurs first.
Incidence of Toxicity During Chemoradiation Therapy	Planned 7 weeks during chemoradiotherapy	Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
Incidence of Toxicity During Maintenance Therapy	Planned 12 months of maintenance with Vorinostat	Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience

Secondary Outcome Measures

Name	Time	Method
Overall Survival	2 years after study enrollment	Time from enrollment to death or last follow-up, whichever occurs first.
Change in H3 and H4 Acetylation Levels in PBMCs	Baseline to up to 7 weeks	Degree of acetylation in peripheral blood monocytes will be divided into quartiles and coded as none, mild, moderation or marked.
Change in NHEJ Activity in PBMCs	Baseline to up to 7 weeks	Descriptive statistics will be used to summarize the biological/laboratory measures and the changes in these measures across time-points.
Levels of DNA Repair Proteins in Paraffin-embedded Blocks, Measured Via Immunohistochemistry or Western Analysis	Baseline	For immunohistochemistry from tumor blocks, the intensity will be graded from 1 to 3; for Western analysis, a percentage of the intensity relative to the tumor with the highest level will be measured.

Trial Locations

Locations (180): Valley Children's Hospital
🇺🇸
Madera, California, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Cedars Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Bozeman Deaconess Hospital
🇺🇸
Bozeman, Montana, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Minor and James Medical PLLC
🇺🇸
Seattle, Washington, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
University of Washington Medical Center - Montlake
🇺🇸
Seattle, Washington, United States
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Kaiser Permanente San Leandro
🇺🇸
San Leandro, California, United States
Kaiser Permanente-San Francisco
🇺🇸
San Francisco, California, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
Primary Children's Hospital
🇺🇸
Salt Lake City, Utah, United States
Princess Margaret Hospital for Children
🇦🇺
Perth, Western Australia, Australia
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
Ascension Saint John Hospital
🇺🇸
Detroit, Michigan, United States
Legacy Emanuel Children's Hospital
🇺🇸
Portland, Oregon, United States
Swedish Medical Center-First Hill
🇺🇸
Seattle, Washington, United States
Highland General Hospital
🇺🇸
Oakland, California, United States
Alta Bates Summit Medical Center - Summit Campus
🇺🇸
Oakland, California, United States
Kaiser Permanente-San Rafael
🇺🇸
San Rafael, California, United States
Nemours Children's Clinic - Pensacola
🇺🇸
Pensacola, Florida, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸
Santa Clara, California, United States
Kaiser Permanente-Santa Rosa
🇺🇸
Santa Rosa, California, United States
Margaret R Pardee Memorial Hospital
🇺🇸
Hendersonville, North Carolina, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States
CoxHealth South Hospital
🇺🇸
Springfield, Missouri, United States
Providence Hospital
🇺🇸
Mobile, Alabama, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Highlands Oncology Group
🇺🇸
Rogers, Arkansas, United States
Kaiser Permanente-Deer Valley Medical Center
🇺🇸
Antioch, California, United States
Kaiser Permanente Downey Medical Center
🇺🇸
Downey, California, United States
Kaiser Permanente-Fremont
🇺🇸
Fremont, California, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸
Long Beach, California, United States
Kaiser Permanente-Fresno
🇺🇸
Fresno, California, United States
Contra Costa Regional Medical Center
🇺🇸
Martinez, California, United States
El Camino Hospital
🇺🇸
Mountain View, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸
Oakland, California, United States
Bay Area Tumor Institute
🇺🇸
Oakland, California, United States
Kaiser Permanente-Oakland
🇺🇸
Oakland, California, United States
Kaiser Permanente-Richmond
🇺🇸
Richmond, California, United States
Kaiser Permanente-Roseville
🇺🇸
Roseville, California, United States
Kaiser Permanente-Santa Teresa-San Jose
🇺🇸
San Jose, California, United States
UCSF Medical Center-Mission Bay
🇺🇸
San Francisco, California, United States
Doctors Medical Center- JC Robinson Regional Cancer Center
🇺🇸
San Pablo, California, United States
Kaiser Permanente Medical Center-Vacaville
🇺🇸
Vacaville, California, United States
Kaiser Permanente-South San Francisco
🇺🇸
South San Francisco, California, United States
Kaiser Permanente-Stockton
🇺🇸
Stockton, California, United States
Kaiser Permanente-Vallejo
🇺🇸
Vallejo, California, United States
Kaiser Permanente-Walnut Creek
🇺🇸
Walnut Creek, California, United States
Smilow Cancer Hospital Care Center at Saint Francis
🇺🇸
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
Lee Memorial Health System
🇺🇸
Fort Myers, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸
Jacksonville, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Memorial Health University Medical Center
🇺🇸
Savannah, Georgia, United States
Saint Anthony's Health
🇺🇸
Alton, Illinois, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
Edward Hospital/Cancer Center
🇺🇸
Naperville, Illinois, United States
Good Samaritan Regional Health Center
🇺🇸
Mount Vernon, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Memorial Medical Center
🇺🇸
Springfield, Illinois, United States
Beaumont Hospital - Dearborn
🇺🇸
Dearborn, Michigan, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸
Flint, Michigan, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
Lake Huron Medical Center
🇺🇸
Port Huron, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸
Livonia, Michigan, United States
Saint John Macomb-Oakland Hospital
🇺🇸
Warren, Michigan, United States
University of Minnesota/Masonic Cancer Center
🇺🇸
Minneapolis, Minnesota, United States
Cardinal Glennon Children's Medical Center
🇺🇸
Saint Louis, Missouri, United States
Saint Francis Medical Center
🇺🇸
Cape Girardeau, Missouri, United States
Singing River Hospital
🇺🇸
Pascagoula, Mississippi, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸
Saint Louis, Missouri, United States
Cancer Research for the Ozarks NCORP
🇺🇸
Springfield, Missouri, United States
Saint Louis-Cape Girardeau CCOP
🇺🇸
Saint Louis, Missouri, United States
Billings Clinic Cancer Center
🇺🇸
Billings, Montana, United States
Saint Vincent Healthcare
🇺🇸
Billings, Montana, United States
Montana Cancer Consortium NCORP
🇺🇸
Billings, Montana, United States
Saint Vincent Frontier Cancer Center
🇺🇸
Billings, Montana, United States
Benefis Healthcare- Sletten Cancer Institute
🇺🇸
Great Falls, Montana, United States
Saint Peter's Community Hospital
🇺🇸
Helena, Montana, United States
Great Falls Clinic
🇺🇸
Great Falls, Montana, United States
Kalispell Regional Medical Center
🇺🇸
Kalispell, Montana, United States
CHI Health Good Samaritan
🇺🇸
Kearney, Nebraska, United States
Morristown Medical Center
🇺🇸
Morristown, New Jersey, United States
Saint Patrick Hospital - Community Hospital
🇺🇸
Missoula, Montana, United States
Saint Peter's University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
🇺🇸
Newark, New Jersey, United States
Overlook Hospital
🇺🇸
Summit, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸
New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸
New York, New York, United States
Iredell Memorial Hospital
🇺🇸
Statesville, North Carolina, United States
Mission Hospital
🇺🇸
Asheville, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Wayne Memorial Hospital
🇺🇸
Goldsboro, North Carolina, United States
Cleveland Clinic Akron General
🇺🇸
Akron, Ohio, United States
Children's Hospital Medical Center of Akron
🇺🇸
Akron, Ohio, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Saint Charles Health System
🇺🇸
Bend, Oregon, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Penn State Children's Hospital
🇺🇸
Hershey, Pennsylvania, United States
Prisma Health Richland Hospital
🇺🇸
Columbia, South Carolina, United States
Saint Francis Hospital
🇺🇸
Greenville, South Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸
Greenville, South Carolina, United States
Carolina Blood and Cancer Care Associates PA-Lancaster
🇺🇸
Lancaster, South Carolina, United States
Greenville Cancer Treatment Center
🇺🇸
Greenville, South Carolina, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Saint Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸
Houston, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸
San Antonio, Texas, United States
Cancer Care Center at Island Hospital
🇺🇸
Anacortes, Washington, United States
Harrison HealthPartners Hematology and Oncology-Bremerton
🇺🇸
Bremerton, Washington, United States
Children's Hospital of The King's Daughters
🇺🇸
Norfolk, Virginia, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸
Bellingham, Washington, United States
Highline Medical Center-Main Campus
🇺🇸
Burien, Washington, United States
Kadlec Clinic Hematology and Oncology
🇺🇸
Kennewick, Washington, United States
Skagit Valley Hospital
🇺🇸
Mount Vernon, Washington, United States
Harrison HealthPartners Hematology and Oncology-Poulsbo
🇺🇸
Poulsbo, Washington, United States
Harborview Medical Center
🇺🇸
Seattle, Washington, United States
PeaceHealth United General Medical Center
🇺🇸
Sedro-Woolley, Washington, United States
Kaiser Permanente Washington
🇺🇸
Seattle, Washington, United States
Evergreen Hematology and Oncology PS
🇺🇸
Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸
Tacoma, Washington, United States
Wenatchee Valley Hospital and Clinics
🇺🇸
Wenatchee, Washington, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
🇺🇸
Yakima, Washington, United States
Royal Children's Hospital-Brisbane
🇦🇺
Herston, Queensland, Australia
Welch Cancer Center
🇺🇸
Sheridan, Wyoming, United States
Queensland Children's Hospital
🇦🇺
South Brisbane, Queensland, Australia
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
Saint Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸
Grand Rapids, Michigan, United States
Ascension Saint Mary's Hospital
🇺🇸
Saginaw, Michigan, United States
Michigan Cancer Research Consortium NCORP
🇺🇸
Ann Arbor, Michigan, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Southeast Clinical Oncology Research Consortium NCORP
🇺🇸
Winston-Salem, North Carolina, United States
Kaiser Permanente-South Sacramento
🇺🇸
Sacramento, California, United States
Kaiser Permanente - Sacramento
🇺🇸
Sacramento, California, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
AdventHealth Orlando
🇺🇸
Orlando, Florida, United States
Arnold Palmer Hospital for Children
🇺🇸
Orlando, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸
Orlando, Florida, United States
Orlando Health Cancer Institute
🇺🇸
Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸
Orlando, Florida, United States
Norton Children's Hospital
🇺🇸
Louisville, Kentucky, United States
Kaiser Permanente-Redwood City
🇺🇸
Redwood City, California, United States
Spartanburg Medical Center
🇺🇸
Spartanburg, South Carolina, United States
Glacier Oncology PLLC
🇺🇸
Kalispell, Montana, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸
Boise, Idaho, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Mercy Hospital Springfield
🇺🇸
Springfield, Missouri, United States
AnMed Health Hospital
🇺🇸
Anderson, South Carolina, United States
Children's Mercy Hospitals and Clinics
🇺🇸
Kansas City, Missouri, United States
University of Hawaii Cancer Center
🇺🇸
Honolulu, Hawaii, United States
Kaiser Permanente Moanalua Medical Center
🇺🇸
Honolulu, Hawaii, United States
Blank Children's Hospital
🇺🇸
Des Moines, Iowa, United States
Baptist Health Lexington
🇺🇸
Lexington, Kentucky, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
Cancer Care Northwest - Spokane South
🇺🇸
Spokane, Washington, United States