Low-Dose or High-Dose Vincristine and Combination Chemotherapy in Treating Young Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia
- Conditions
- L1 Childhood Acute Lymphoblastic LeukemiaL2 Childhood Acute Lymphoblastic LeukemiaB-cell Childhood Acute Lymphoblastic LeukemiaIntermediate Risk Recurrent Childhood Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT00381680
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
This randomized phase III trial is studying low-dose vincristine to see how well it works compared with high-dose vincristine when given together with different combination chemotherapy regimens in treating young patients with intermediate-risk relapsed B-cell acute lymphoblastic leukemia. 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. Giving more than one drug (combination chemotherapy) and giving the drugs in different ways and different doses may kill more cancer cells..
- Detailed Description
PRIMARY OBJECTIVES:
I. Determine the efficacy of an intensive chemotherapy regimen (based on POG-9412) for pediatric patients with intermediate-risk relapsed B-precursor acute lymphoblastic leukemia.
SECONDARY OBJECTIVES:
I. To determine levels of minimal residual disease (MRD) present at the end of the first \& third blocks of Induction and determine if higher MRD levels at these times identify patients at higher risk of relapse who might be candidates for alternative therapies in future trials.
II. To determine whether common polymorphisms in candidate genes are associated with the frequency of vincristine adverse effects (peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion \[SIADH\], or constipation) and with anti-leukemic response (level of end-Induction MRD).
III. Compare, descriptively, the outcomes of patients treated with combination chemotherapy vs those treated with matched sibling-related donor hematopoietic stem cell transplantation (for those with eligible donors).
IV. To use deoxyribonucleic acid (DNA) arrays to characterize patterns of gene expression that predict treatment failure, and to compare gene expression profiles at the time of relapse with those at initial diagnosis to gain an understanding of the pathways that may be involved in disease resistance.
OUTLINE: This is a multicenter, randomized study. Patients are randomized to 1 of 2 treatment regimens (randomization closed as of 09/2010).
INDUCTION THERAPY 1 (WEEKS 1-5):
Regimen A: Patients receive low-dose vincristine intravenously (IV) on days 1, 8, 15, and 22; prednisone orally (PO) 3 times daily (TID) on days 1-28; doxorubicin hydrochloride IV over 15 minutes on day 1; pegaspargase intramuscularly (IM) on days 2, 8, 15, and 22; cytarabine intrathecally (IT) on day 1; and methotrexate IT\* on days 15 and 29.
Regimen B: (closed to accrual as of 09/2010)\*\*\*: Patients receive high-dose vincristine IV on days 1, 8, 15, and 22 and prednisone, doxorubicin hydrochloride, pegaspargase, cytarabine, and methotrexate\* as in Regimen A.
NOTE: \*Central nervous system (CNS)-positive patients do not receive methotrexate IT. In both arms, CNS-positive patients receive intrathecal triple therapy (ITT) comprising methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1, 8, 15, 22, and 29. CNS-positive patients not achieving remission after induction therapy 1 receive one additional dose of ITT on day 36. Patients in both arms then proceed to induction therapy 2\*\*.
NOTE: \*\*Patients who are CNS-positive at relapse receive induction therapy 3 BEFORE induction therapy 2.
NOTE: \*\*\*Patients already enrolled on Regimen B are crossover to Regimen A.
INDUCTION THERAPY 2 (WEEKS 6-10 or 7-11): Once blood counts recover, all patients receive etoposide phosphate IV over = 1 hour and cyclophosphamide IV over 1 hour on days 1-5; high-dose methotrexate IV continuously over 24 hours on day 22; leucovorin calcium IV or PO beginning 42 hours after start of high-dose methotrexate and continuing every 6 hours for at least 3 doses; and methotrexate IT\* on days 1 and 22. Patients also receive filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 6 and continuing until blood counts recover.
NOTE: \*CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on days 1 and 22. Patients with testicular-relapse with persistent testicular disease at the end of induction therapy 1 undergo testicular radiotherapy once daily (QD), 5 days a week, for 12 days during induction therapy 2\*\*.
NOTE: \*\*Radiotherapy should be completed before beginning high-dose methotrexate (week 9) chemotherapy.
All patients then proceed to induction therapy 3.
INDUCTION THERAPY 3 (WEEKS 11-15 or 12-16): All patients receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9, and asparaginase IM on days 2 and 9. Patients also receive G-CSF IV or SC beginning on day 10 and continuing until blood counts recover. Patients with a suitable HLA-matched related donor are removed from study and proceed to stem cell transplantation. Patients without a suitable HLA-matched related donor proceed to intensification therapy 1 (as per their randomized regimen in induction therapy 1).
INTENSIFICATION THERAPY 1 (WEEKS 16-27 or 17-28):
Regimen A: Patients receive low-dose vincristine IV and high-dose methotrexate IV continuously over 24 hours on day 1; leucovorin calcium IV or orally beginning 42 hours after start of high-dose methotrexate and continuing every 6 hours for at least 3 doses; oral mercaptopurine once daily on days 2-6; etoposide phosphate IV over ≥ 1 hour and cyclophosphamide IV over 1 hour on day 8; and methotrexate IT\* on day 15. Treatment repeats every 21 days for 4 courses (with the exception of IT methotrexate which repeats for only 3 courses).
Regimen B: Patients receive high-dose vincristine IV on day 1 and high-dose methotrexate, leucovorin calcium, mercaptopurine, etoposide phosphate, cyclophosphamide, and methotrexate IT\* as in Regimen A. (closed to accrual as of 09/2010)
NOTE: \*CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on day 15. ITT repeats every 3 weeks for 3 courses.
NOTE: \*\* Patients already enrolled on Regimen B are crossover to Regimen A.
Patients in both regimens then proceed to reinduction therapy (as per their randomized regimen in induction therapy 1).
REINDUCTION THERAPY (WEEKS 28-32 or 29-33):
Regimen A: Patients receive low-dose vincristine IV and doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15, oral dexamethasone twice daily on days 1-7 and 15-21, pegaspargase IM on days 2 and 15, and methotrexate IT\* on days 1 and 28.
Regimen B: Patients receive high-dose vincristine IV on days 1, 8, and 15 and doxorubicin hydrochloride, dexamethasone, pegaspargase, and methotrexate IT\* as in Regimen A. (closed to accrual as of 09/2010)
NOTE: \*CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on days 1 and 28.
NOTE: \*\* Patients already enrolled on Regimen B are crossover to Regimen A. Patients in both regimens then proceed to intensification therapy 2 (as per their randomized regimen in induction therapy 1).
INTENSIFICATION THERAPY 2 (WEEKS 33-56 or 34-57):
Regimen A: Once blood counts recover, patients receive high-dose cytarabine IV over 3 hours on days 1 and 2; pegaspargase IM on day 2; low-dose vincristine IV on days 22 and 29; high-dose methotrexate IV on day 22; leucovorin calcium IV or orally beginning 42 hours after start of high-dose methotrexate and continuing every 6 hours for at least 3 doses; oral mercaptopurine once daily on days 23-27; etoposide phosphate IV over ≥ 1 hour and cyclophosphamide IV over 1 hour on day 29; and methotrexate IT\* on day 36. Patients also receive G-CSF IV or SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 42 days for 4 courses (with the exception of IT methotrexate which only repeats for 3 courses).
Regimen B: Patients receive high-dose cytarabine, high-dose methotrexate, leucovorin calcium, pegaspargase, mercaptopurine, etoposide phosphate, cyclophosphamide, methotrexate IT\*, and G-CSF as in Regimen A. Patients also receive high-dose vincristine IV on days 22 and 29.
NOTE: \*CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on day 36. Treatment repeats every 6 weeks for 3 courses.
Patients in both regimens then proceed to maintenance therapy (as per their randomized regimen in induction therapy 1).
MAINTENANCE THERAPY (week 57-106 or 58-107):
Regimen A: Patients receive methotrexate IT on day 1\* and then PO on days 8, 15, 22, 29, and 36; mercaptopurine PO QD on days 1-42; dexamethasone PO twice daily (BID) on days 1-5; and low-dose vincristine IV and cyclophosphamide IV over 1 hour on days 43, 50, 57, and 64. Treatment repeats every 70 days for 5 courses.
Regimen B: Patients receive methotrexate\*, mercaptopurine, dexamethasone, and cyclophosphamide as in Regimen A. Patients also receive high-dose vincristine IV on days 43, 50, 57, and 64.
NOTE: \*CNS-positive patients receive methotrexate IT on day 1, instead of oral methotrexate.
Beginning in week 1 of the first maintenance therapy course, patients with CNS relapse undergo cranial radiotherapy QD, 5 days a week, for 10 days. Patients with CNS relapse do not receive any IT therapy during maintenance therapy.
After completion of study therapy, patients are followed periodically for 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 275
-
Diagnosis of acute lymphoblastic leukemia (ALL)
-
Bone marrow with > 25% L1 or L2 lymphoblasts (M3 marrow)
- Patients with > 25% L3 marrow lymphoblasts and/or evidence of c-myc translocation are not eligible (considered Burkitt's or mature B-cell leukemia)
-
-
Intermediate-risk relapsed disease, meeting 1 of the following criteria:
- Bone marrow relapse ≥ 36 months after initial diagnosis (defined as M3 marrow after previous remission from ALL)
- Combined bone marrow and extramedullary (CNS* and/or testicular**) relapse ≥ 36 months after initial diagnosis
- Isolated extramedullary (CNS* and/or testicular**) relapse < 18 months after initial diagnosis
-
The following subtypes are not allowed:
- T-lineage ALL
- Mature B-cell (Burkitt's) leukemia (defined as L3 morphology and/or evidence of c-myc translocation)
- Philadelphia-chromosome positive disease
-
No Down syndrome (trisomy 21)
-
Shortening fraction >= 27% by echocardiogram OR ejection fraction >= 50% by radionuclide angiogram
-
Bilirubin < 3.0 mg/dL
-
Not pregnant
-
Fertile patients must use effective contraception
-
No history of peripheral neuropathy >= grade 3 within the past month
-
No toxicity (i.e. peripheral neuropathy) >= grade 3 attributable to vincristine within the past month
-
At least 5 days since prior intrathecal chemotherapy
-
No prior hematopoietic stem cell or marrow transplantation
-
No prior cranial radiotherapy > 1200 cGy (for patients with CNS relapse)
-
No concurrent stem cell transplant
-
No concurrent alternative therapy
-
No concurrent itraconazole in patients receiving vincristine
-
No concurrent intensity-modulated radiotherapy
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regimen A: Standard vincristine dosing vincristine sulfate See detailed description. Regimen A: Standard vincristine dosing filgrastim See detailed description. Arm B: Randomized High Dose Vincristine regimen leucovorin calcium See detailed description. Closed to accrual as of 09/2010). Regimen A: Standard vincristine dosing leucovorin calcium See detailed description. Arm B: Randomized High Dose Vincristine regimen filgrastim See detailed description. Closed to accrual as of 09/2010). Arm B: Randomized High Dose Vincristine regimen vincristine sulfate See detailed description. Closed to accrual as of 09/2010). Arm B: Randomized High Dose Vincristine regimen etoposide See detailed description. Closed to accrual as of 09/2010). Regimen A: Standard vincristine dosing asparaginase See detailed description. Regimen A: Standard vincristine dosing doxorubicin hydrochloride See detailed description. Regimen A: Standard vincristine dosing prednisone See detailed description. Regimen A: Standard vincristine dosing pegaspargase See detailed description. Regimen A: Standard vincristine dosing cytarabine See detailed description. Regimen A: Standard vincristine dosing methotrexate See detailed description. Regimen A: Standard vincristine dosing dexamethasone See detailed description. Regimen A: Standard vincristine dosing cyclophosphamide See detailed description. Regimen A: Standard vincristine dosing etoposide See detailed description. Regimen A: Standard vincristine dosing mercaptopurine See detailed description. Arm B: Randomized High Dose Vincristine regimen prednisone See detailed description. Closed to accrual as of 09/2010). Arm B: Randomized High Dose Vincristine regimen doxorubicin hydrochloride See detailed description. Closed to accrual as of 09/2010). Arm B: Randomized High Dose Vincristine regimen cytarabine See detailed description. Closed to accrual as of 09/2010). Arm B: Randomized High Dose Vincristine regimen pegaspargase See detailed description. Closed to accrual as of 09/2010). Arm B: Randomized High Dose Vincristine regimen methotrexate See detailed description. Closed to accrual as of 09/2010). Arm B: Randomized High Dose Vincristine regimen dexamethasone See detailed description. Closed to accrual as of 09/2010). Arm B: Randomized High Dose Vincristine regimen cyclophosphamide See detailed description. Closed to accrual as of 09/2010). Arm B: Randomized High Dose Vincristine regimen asparaginase See detailed description. Closed to accrual as of 09/2010). Arm B: Randomized High Dose Vincristine regimen mercaptopurine See detailed description. Closed to accrual as of 09/2010).
- Primary Outcome Measures
Name Time Method Event Free Survival. EFS 3 years after enrollment Percentage of patients who were event free at 3 years among those on Standard VCR dosing who did not undergo Hematopoietic Stem Cell Transplant (SCT).
- Secondary Outcome Measures
Name Time Method Gene Expression Profile Up to 36 months Percent of unfavorable gene expression profile of early versus late marrow relapse.
Frequency and Severity of Adverse Effects Up to 107 weeks Percentage of patients who developed at least 1 episode of grade 2 to 4 neuropathy.
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 1 End of Block 1 (35 days) of Induction therapy Percentage of patients who had minimal residual disease (MRD) \< 0.01% among those with isolated BM or combined BM relapse \>= 36 months and had successful MRD determinations at End Block 1
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 3 End of Block 3 (105 days) of Induction therapy Percentage of patients who had minimal residual disease (MRD) \< 0.01% among those with isolated BM or combined BM relapse \>= 36 months and had successful MRD determinations at End Block 3.
Event Free Survival (EFS) 3 years Percentage of patients who were event free at 3 years among those with isolated BM or combined BM relapse \>= 36 months.
Adjusted Event Free Survival 3 years Adjusted percentage of patients who were event free at 3 years. For patients who received matched donor SCT, EFS was adjusted to start from the actual SCT date. For patients who did not undergo SCT, EFS was adjusted to start from median time to SCT based on patients who received matched related SCT (where patients who had events prior to SCT date were excluded from the calculation of median time to SCT).
Trial Locations
- Locations (173)
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Childrens Memorial Hospital
🇺🇸Chicago, Illinois, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Hawaii
🇺🇸Honolulu, Hawaii, United States
Children's Oncology Group
🇺🇸Arcadia, California, United States
Southern Illinois University
🇺🇸Springfield, Illinois, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
New York University Langone Medical Center
🇺🇸New York, New York, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Baptist Hospital of Miami
🇺🇸Miami, Florida, United States
Saint Vincent Hospital and Health Services
🇺🇸Indianapolis, Indiana, United States
Nevada Cancer Research Foundation CCOP
🇺🇸Las Vegas, Nevada, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
University of California San Francisco Medical Center-Parnassus
🇺🇸San Francisco, California, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
New York Medical College
🇺🇸Valhalla, New York, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States
Lombardi Comprehensive Cancer Center at Georgetown University
🇺🇸Washington, District of Columbia, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Hospital Sainte-Justine
🇨🇦Montreal, Quebec, Canada
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
T C Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Michigan State University - Breslin Cancer Center
🇺🇸Lansing, Michigan, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
Saint Luke's Mountain States Tumor Institute
🇺🇸Boise, Idaho, United States
UMDNJ - Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Kalamazoo Center for Medical Studies
🇺🇸Kalamazoo, Michigan, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
West Virginia University Charleston
🇺🇸Charleston, West Virginia, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
Legacy Emanuel Children's Hospital
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Advocate Hope Children's Hospital
🇺🇸Oak Lawn, Illinois, United States
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
City of Hope Medical Center
🇺🇸Duarte, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Miller Children's Hospital
🇺🇸Long Beach, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Childrens Hospital of Orange County
🇺🇸Orange, California, United States
Children's Hospital and Research Center at Oakland
🇺🇸Oakland, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Sutter General Hospital
🇺🇸Sacramento, California, United States
Santa Barbara Cottage Hospital
🇺🇸Santa Barbara, California, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Nemours Children's Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Miami Children's Hospital
🇺🇸Miami, Florida, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Saint Joseph Children's Hospital of Tampa
🇺🇸Tampa, Florida, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Georgia Regents University
🇺🇸Augusta, Georgia, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Maine Children's Cancer Program
🇺🇸Scarborough, Maine, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
University of Maryland Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Saint John's Mercy Medical Center
🇺🇸Saint Louis, Missouri, United States
University of Missouri-Columbia
🇺🇸Columbia, Missouri, United States
University of Minnesota Medical Center-Fairview
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸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
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Mission Hospitals Inc
🇺🇸Asheville, North Carolina, United States
Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
The Children's Medical Center of Dayton
🇺🇸Dayton, Ohio, United States
Mercy Children's Hospital
🇺🇸Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Penn State Hershey Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Legacy Emanuel Hospital and Health Center
🇺🇸Portland, Oregon, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, 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
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
Greenville Cancer Treatment Center
🇺🇸Greenville, South Carolina, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Texas Tech University Health Science Center-Amarillo
🇺🇸Amarillo, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Childrens Hospital-King's Daughters
🇺🇸Norfolk, Virginia, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
Carilion Clinic Children's Hospital
🇺🇸Roanoke, Virginia, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸Tacoma, Washington, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Saint Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Chedoke-McMaster Hospitals
🇨🇦Hamilton, Ontario, Canada
Children's Hospital
🇨🇦London, Ontario, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Swiss Pediatric Oncology Group - Lausanne
🇨🇭Lausanne, Switzerland
Swiss Pediatric Oncology Group - Bern
🇨🇭Bern, Switzerland
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
M D Anderson Cancer Center- Orlando
🇺🇸Orlando, Florida, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
Nemours Childrens Clinic - Orlando
🇺🇸Orlando, Florida, United States
Yale University
🇺🇸New Haven, Connecticut, United States
The Childrens Mercy Hospital
🇺🇸Kansas City, Missouri, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Raymond Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Children's Hospital-Main Campus
🇺🇸New Orleans, Louisiana, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States