Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma
- Conditions
- Childhood Nodular Lymphocyte Predominant Hodgkin LymphomaStage III Childhood Hodgkin LymphomaStage IV Childhood Hodgkin Lymphoma
- Interventions
- Biological: bleomycin sulfateBiological: filgrastim
- Registration Number
- NCT01026220
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. To maintain the overall survival (as defined by 4-year "second-event" free survival) for subjects with high risk Hodgkin lymphoma at or above 95%.
SECONDARY OBJECTIVES:
I. To maintain 3-year event-free survival for subjects with high risk Hodgkin lymphoma at or above 93%.
II. To maintain comparable overall survival (as defined by 4-year "second-event" free survival) between subjects with high risk Hodgkin lymphoma who have a rapid or slow response to the initial 2 cycles of ABVE-PC\* by intensifying therapy through the addition of 2 cycles of ifosfamide/vinorelbine in those with a slow early response.
III. To investigate whether very early response assessment measured by FDG-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.
IV. To describe the patterns of relapse after ABVE-PC\* and risk-adapted radiotherapy.
OUTLINE: This is a multicenter study.
INDUCTION THERAPY (ABVE-PC): Patients receive doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2, bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8, etoposide phosphate IV over 1-2 hours on days 1-3, oral prednisone twice daily on days 1-7, and filgrastim\* SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
NOTE: \*Patients do not receive filgrastim on day 8.
Patients undergo clinical restaging and response assessment after 2 courses of induction therapy. Patients with rapid early response (RER) or slow early response (SER) proceed to consolidation therapy. Patients with progressive disease go off study.
CONSOLIDATION THERAPY: Patients are assigned to 1 of 2 consolidation therapy regimens based on response to induction therapy. Patients who develop progressive disease after induction are taken off protocol therapy.
REGIMEN I (RER): Patients receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
REGIMEN II (SER): Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-30 minutes on days 1 and 5, and filgrastim SC or IV daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
Patients with a continued response after completion of consolidation therapy proceed to risk-adapted radiotherapy.
RISK-ADAPTED RADIOTHERAPY: Beginning at 3 weeks after completion of consolidation chemotherapy, patients undergo radiotherapy once daily, 5 days a week, for 3 weeks (14 fractions) in the absence of unacceptable toxicity or disease progression. Patients classified as RER receive radiation therapy only to sites of bulky disease. Patients classified as SER receive radiation therapy to sites of bulky disease and areas that remain FDG-PET avid after induction therapy.
After completion of study therapy, patients are followed up periodically for 10 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 166
-
Pathologically confirmed newly diagnosed Hodgkin lymphoma (HL) meeting one of the following criteria:
- Classical disease
- Nodular lymphocyte-predominant disease
-
Stage III or IV disease with B symptoms, as defined by ≥ 1 of the following:
- Unexplained weight loss > 10% within the past 6 months
- Unexplained recurrent fever > 38°C within the past month
- Recurrent drenching night sweats within the past month
-
Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:
- 0.4 mg/dL (1 to 5 months)
- 0.5 mg/dL (6 to 11 months)
- 0.6 mg/dL (12 to 23 months)
- 0.8 mg/dL (2 to 5 years)
- 1 mg/dL (6 to 9 years)
- 1.2 mg/dL (10 to 12 years)
- 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years)
- 1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years)
-
Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
-
AST or ALT < 2.5 times ULN for age
-
Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 50% by MUGA (unless due to large mediastinal mass from HL)
-
FEV_1/FVC > 60% by pulmonary function tests (PFT) (unless due to large mediastinal mass fromHL)
-
For children who are unable to cooperate for PFTs, the criteria are:
- No evidence of dyspnea at rest
- No exercise intolerance
- Pulse oximetry > 92% on room air
-
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
No pathologic prolongation of QTc interval (> 450 milliseconds) on 12-lead ECG
-
No prior chemotherapy, biological response modifiers (e.g., monoclonal antibody therapy), or radiotherapy
-
At least 28 days since prior corticosteroids except for emergent treatment for respiratory distress or spinal cord compression, or for treatment of allergy to contrast agent required for CT scan
-
No other concurrent cancer chemotherapy or immunomodulating agents (including steroids)
- Concurrent corticosteroid therapy as treatment or prophylaxis for anaphylactic reactions allowed
-
No concurrent pegfilgrastim
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regimen I (consolidation therapy) bleomycin sulfate Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Regimen I (consolidation therapy) liposomal vincristine sulfate Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Regimen I (consolidation therapy) prednisone Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Regimen I (consolidation therapy) filgrastim Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Regimen II (consolidation therapy) bleomycin sulfate Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Regimen II (consolidation therapy) doxorubicin hydrochloride Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Regimen II (consolidation therapy) cyclophosphamide Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Regimen II (consolidation therapy) etoposide phosphate Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Regimen II (consolidation therapy) filgrastim Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Induction: all patient doxorubicin hydrochloride All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease. Induction: all patient liposomal vincristine sulfate All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease. Induction: all patient filgrastim All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease. Regimen I (consolidation therapy) etoposide phosphate Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Regimen II (consolidation therapy) vinorelbine tartrate Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Induction: all patient etoposide phosphate All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease. Regimen II (consolidation therapy) liposomal vincristine sulfate Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Regimen I (consolidation therapy) doxorubicin hydrochloride Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Regimen I (consolidation therapy) cyclophosphamide Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Regimen II (consolidation therapy) prednisone Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Regimen II (consolidation therapy) ifosfamide Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Induction: all patient cyclophosphamide All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease. Induction: all patient prednisone All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease.
- Primary Outcome Measures
Name Time Method Second-event-free Survival At 4 years from enrollment Second event here is defined as any relapse/progression of Hodgkin Lymphoma (HL) or a previously reported second malignant neoplasm (SMN), a new SMN, or death after a first event which can be relapse/progression of HL, SMN, biopsy-proven HL following completion of Consolidation for Slow Early Response (SER) patient, positive bilateral bone marrow biopsy following completion of Consolidation for Stage IV patient, or death. If death occurs as the 1st event, it also counts as the 2nd event.
Safety Analysis and Monitoring of Toxic Death Within 30 days of protocol treatment at median follow-up of 48 months (range: 1 to 70 months). The primary endpoint for safety analysis and monitoring is toxic death, which is death primarily attributable to treatment.
- Secondary Outcome Measures
Name Time Method Event Free Survival At 3 years from enrollment Survival from enrollment to first event: relapse/progression, second malignancy, or death.
Second-event-free Survival At 4 years from enrollment Second event here is defined as any relapse/progression of Hodgkin Lymphoma (HL) or a previously reported second malignant neoplasm (SMN), a new SMN, or death after a first event which can be relapse/progression of HL, SMN, biopsy-proven HL following completion of Consolidation for Slow Early Response (SER) patient, positive bilateral bone marrow biopsy following completion of Consolidation for Stage IV patient, or death. If death occurs as the 1st event, it also counts as the 2nd event.
Event-free Survival for Rapid Early Response (RER) Positron Emission Tomography(PET)-1 Positive, RER PET-1 Negative 3 years from enrollment To investigate whether very early response assessment measured by Fluorodeoxyglucose-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.
Relapse-free Survival 3 years from enrollment A description, survival to relapse, of patterns of relapse after Doxorubicin, Bleomycin, Vincristine, Etoposide - Prednisone, Cyclophosphamide (ABVE-PC) and risk-adapted radiotherapy.
Grade 3 and 4 Non-hematologic Toxicities During Protocol Therapy During and after completion of study treatment. The number of patients that experience Common Terminology Criteria (CTC) Version 4 grade 3 or higher non-hematologic toxicity at any time during protocol therapy.
Overall Survival At 3 years from enrollment Survival from enrollment to death.
Trial Locations
- Locations (177)
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Lombardi Comprehensive Cancer Center at Georgetown University
🇺🇸Washington, District of Columbia, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
University of Hawaii
🇺🇸Honolulu, Hawaii, United States
Childrens Hospital of Orange County
🇺🇸Orange, California, United States
Georgia Regents University
🇺🇸Augusta, Georgia, United States
Children's Hospital and Research Center at Oakland
🇺🇸Oakland, California, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸Oak Lawn, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Memorial Healthcare System - Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
UMDNJ - Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Sanford Medical Center-Fargo
🇺🇸Fargo, North Dakota, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Mission Hospital-Memorial Campus
🇺🇸Asheville, North Carolina, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸Tacoma, Washington, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Sydney Children's Hospital
🇦🇺Randwick, New South Wales, Australia
Centre Hospitalier Universitaire de Quebec
🇨🇦Ste-Foy, Quebec, Canada
Saint Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
Schneider Children's Medical Center of Israel
🇮🇱Petah Tikua, Israel
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Women's and Children's Hospital-Adelaide
🇦🇺North Adelaide, South Australia, Australia
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
University of Vermont
🇺🇸Burlington, Vermont, United States
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
The Montreal Children's Hospital of the MUHC
🇨🇦Montreal, Quebec, Canada
Childrens Hospital-King's Daughters
🇺🇸Norfolk, Virginia, United States
Chaim Sheba Medical Center
🇮🇱Tel Hashomer, Israel
West Virginia University Charleston
🇺🇸Charleston, West Virginia, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Miami Children's Hospital
🇺🇸Miami, Florida, United States
Baptist Hospital of Miami
🇺🇸Miami, Florida, United States
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Saint Vincent Hospital and Health Services
🇺🇸Indianapolis, Indiana, United States
Nevada Cancer Research Foundation CCOP
🇺🇸Las Vegas, Nevada, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota Medical Center-Fairview
🇺🇸Minneapolis, Minnesota, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
Legacy Emanuel Hospital and Health Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Saint Joseph Children's Hospital of Tampa
🇺🇸Tampa, Florida, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Miller Children's Hospital
🇺🇸Long Beach, California, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of South Alabama
🇺🇸Mobile, Alabama, United States
City of Hope Medical Center
🇺🇸Duarte, California, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
University of California San Francisco Medical Center-Parnassus
🇺🇸San Francisco, California, United States
Santa Barbara Cottage Hospital
🇺🇸Santa Barbara, California, United States
Nemours Children's Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
UF Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Saint Luke's Mountain States Tumor Institute
🇺🇸Boise, Idaho, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Children's Hospital-Main Campus
🇺🇸New Orleans, Louisiana, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Missouri - Ellis Fischel
🇺🇸Columbia, Missouri, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Columbia Regional
🇺🇸Columbia, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
Weill Medical College of Cornell University
🇺🇸New York, New York, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
The Toledo Hospital/Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Children's Oncology Group
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Palmetto Health Richland
🇺🇸Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
Greenville Cancer Treatment Center
🇺🇸Greenville, South Carolina, United States
T C Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦Montreal, Quebec, Canada
San Jorge Children's Hospital
🇵🇷San Juan, Puerto Rico
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Michigan State University Clinical Center
🇺🇸East Lansing, Michigan, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Kalamazoo Center for Medical Studies
🇺🇸Kalamazoo, Michigan, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Penn State Hershey Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
University of California at Davis Cancer Center
🇺🇸Sacramento, California, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Advocate Lutheran General Hospital.
🇺🇸Park Ridge, Illinois, United States
New York Medical College
🇺🇸Valhalla, New York, United States
The Childrens Mercy Hospital
🇺🇸Kansas City, Missouri, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States