Chemotherapy With or Without Additional Chemotherapy and/or Radiation Therapy in Treating Children With Newly Diagnosed Hodgkin's Disease
- Conditions
- Childhood Mixed Cellularity Classical Hodgkin LymphomaStage I Childhood Hodgkin LymphomaStage IV Childhood Hodgkin LymphomaChildhood Lymphocyte-Depleted Classical Hodgkin LymphomaChildhood Nodular Lymphocyte Predominant Hodgkin LymphomaStage II Childhood Hodgkin LymphomaChildhood Nodular Sclerosis Classical Hodgkin LymphomaStage III Childhood Hodgkin Lymphoma
- Interventions
- Biological: Bleomycin SulfateBiological: FilgrastimRadiation: Involved-Field Radiation Therapy
- Registration Number
- NCT00025259
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
This randomized phase III trial is studying different chemotherapy regimens given with or without radiation therapy to compare how well they work in treating children with newly diagnosed Hodgkin's disease. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known if chemotherapy is more effective with or without additional chemotherapy and/or radiation therapy in treating Hodgkin's disease.
- Detailed Description
OBJECTIVES:
I. To compare response-based therapy to standard therapy for intermediate risk Hodgkin disease.
II. To determine whether involved field radiation therapy (IFRT) can be eliminated based upon early and complete response to multiagent chemotherapy.
III. To determine whether the addition of an additional two cycles of chemotherapy (DECA) can improve outcome in those with a slow early response to standard chemotherapy.
IV. To prospectively collect information on the individual prognostic significance of the following presenting factors: erythrocyte sedimentation rate, circulating levels of IL-10, each of the "B" symptoms - fever, night sweats, weight loss, nodal aggregate \> 6 cm, large mediastinal mass \> 1/3 thoracic diameter and number of involved nodal sites, histology, albumin, blood counts, sex and age.
V. To study the reliability and utility of \[18F\] -Fluorodeoxyglucose (FDG) Imaging (PET scans) as an imaging modality in Hodgkin disease.
VI. To determine the frequency and severity of late effects of therapy including thyroid dysfunction, infertility, cardiotoxicity, pulmonary toxicity and second malignant neoplasms.
VII. To serve as the therapeutic companion to biology studies in Hodgkin disease and correlate those results with response to therapy, event free-survival and overall survival.
OUTLINE: This is a randomized, multicenter study.
ARM I (ALL PATIENTS-OFF THERAPY BEFORE CALLBACK-INDUCTION CHEMOTHERAPY \[ABVE-PC\]): Patients receive doxorubicin intravenously (IV) over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or subcutaneously (SC) and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. At the end of initial chemotherapy, patients undergo evaluation for response. Patients with less than 60% disease reduction are considered to have slow early response (SER). Patients with 60% or more disease reduction are considered to have rapid early response (RER).
RER: Patients receive 2 additional courses of ABVE-PC chemotherapy. After completion of treatment, patients are randomized to 1 of 4 treatment arms.
ARM II: Patients with sustained complete response (CR) undergo involved field radiation therapy (IFRT) approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week.
ARM III: Patients with sustained CR receive no further treatment.
ARM IV: Patients with very good partial response (VGPR), partial response (PR) or stable disease (SD) undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week.
ARM V: Patients with progressive disease are taken off therapy and treated their physician's discretion.
SER: Patients are randomized to 1 of 2 treatment arms.
ARM VI: Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, cytarabine IV over 3 hours on days 1-2, and receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, patients then receive 2 additional courses of ABVE-PC chemotherapy.
ARM VII: Patients receive 2 courses of ABVE-PC chemotherapy.
In both SER arms, patients with sustained CR or PR undergo IFRT approximately 3 weeks after the last course of chemotherapy.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1734
-
Patients with newly diagnosed, pathologically confirmed Hodgkin disease (all histologies) are eligible for this protocol if they meet the following clinical stage guidelines:
- All Stage IB regardless of bulk disease
- All Stage IIB regardless of bulk disease
- Stage IA only with bulk disease
- Stage IIA only with bulk disease
- All Stage IAE, IIAE regardless of bulk disease
- All Stage IIIA, IIIAE, IIIAS, IIIAE+S regardless of bulk disease
- All Stage IVA, IVAE regardless of bulk disease
-
May not be staged by laparotomy alone
- Surgically staged patients must also have presurgical staging
-
Bilirubin no greater than 1.5 times normal
-
SGOT or SGPT less than 2.5 times normal
-
Creatinine no greater than 1.5 times normal
-
Creatinine clearance greater than 40 mL/min
-
Radioisotope glomerular filtration rate greater than 70 mL/min
-
Shortening fraction at least 27% by echocardiogram
-
Ejection fraction at least 50% by MUGA
-
No pathologic prolongation of QTc interval on 12-lead electrocardiogram
-
FEV_1/FVC greater than 60% by pulmonary function test
-
Pulse oximetry greater than 94%
-
No evidence of dyspnea at rest
-
No exercise intolerance
-
Adequate venous access
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
No prior chemotherapy
-
At least 1 month since prior corticosteroids except prednisone for respiratory distress
-
No prior radiotherapy
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm III (RER with CR [ABVE-PC]) Vincristine Sulfate Liposome Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR are randomized to receive no further treatment. Arm II (RER with CR [ABVE-PC, IFRT]) Bleomycin Sulfate Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR undergo IFRT approximately 3 weeks after the last day of ABVE course 4. Arm I (Patients off-therapy before callback-Induction only) Vincristine Sulfate Liposome Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Arm II (RER with CR [ABVE-PC, IFRT]) Filgrastim Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR undergo IFRT approximately 3 weeks after the last day of ABVE course 4. Arm IV (RER with less than CR [ABVE-PC, IFRT]) Involved-Field Radiation Therapy Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with VGPR, PR or SD undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week. Arm I (Patients off-therapy before callback-Induction only) Bleomycin Sulfate Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Arm I (Patients off-therapy before callback-Induction only) Filgrastim Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Arm II (RER with CR [ABVE-PC, IFRT]) Involved-Field Radiation Therapy Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR undergo IFRT approximately 3 weeks after the last day of ABVE course 4. Arm III (RER with CR [ABVE-PC]) Bleomycin Sulfate Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR are randomized to receive no further treatment. Arm II (RER with CR [ABVE-PC, IFRT]) Vincristine Sulfate Liposome Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR undergo IFRT approximately 3 weeks after the last day of ABVE course 4. Arm IV (RER with less than CR [ABVE-PC, IFRT]) Vincristine Sulfate Liposome Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with VGPR, PR or SD undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week. Arm VI (SER [DECA, ABVE-PC, IFRT]) Vincristine Sulfate Liposome Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm III (RER with CR [ABVE-PC]) Filgrastim Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR are randomized to receive no further treatment. Arm IV (RER with less than CR [ABVE-PC, IFRT]) Bleomycin Sulfate Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with VGPR, PR or SD undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week. Arm V (RER with PD) Vincristine Sulfate Liposome Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients with PD are taken off therapy. Arm IV (RER with less than CR [ABVE-PC, IFRT]) Filgrastim Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with VGPR, PR or SD undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week. Arm V (RER with PD) Bleomycin Sulfate Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients with PD are taken off therapy. Arm V (RER with PD) Filgrastim Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients with PD are taken off therapy. Arm VI (SER [DECA, ABVE-PC, IFRT]) Bleomycin Sulfate Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VI (SER [DECA, ABVE-PC, IFRT]) Involved-Field Radiation Therapy Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VII (SER [ABVE-PC, IFRT]) Involved-Field Radiation Therapy Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive 2 additional courses of ABVE-PC. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VI (SER [DECA, ABVE-PC, IFRT]) Filgrastim Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VII (SER [ABVE-PC, IFRT]) Bleomycin Sulfate Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive 2 additional courses of ABVE-PC. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VII (SER [ABVE-PC, IFRT]) Filgrastim Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive 2 additional courses of ABVE-PC. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VII (SER [ABVE-PC, IFRT]) Vincristine Sulfate Liposome Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive 2 additional courses of ABVE-PC. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm I (Patients off-therapy before callback-Induction only) Cyclophosphamide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Arm I (Patients off-therapy before callback-Induction only) Doxorubicin Hydrochloride Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Arm I (Patients off-therapy before callback-Induction only) Etoposide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Arm I (Patients off-therapy before callback-Induction only) Prednisone Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Arm II (RER with CR [ABVE-PC, IFRT]) Cyclophosphamide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR undergo IFRT approximately 3 weeks after the last day of ABVE course 4. Arm II (RER with CR [ABVE-PC, IFRT]) Etoposide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR undergo IFRT approximately 3 weeks after the last day of ABVE course 4. Arm II (RER with CR [ABVE-PC, IFRT]) Doxorubicin Hydrochloride Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR undergo IFRT approximately 3 weeks after the last day of ABVE course 4. Arm II (RER with CR [ABVE-PC, IFRT]) Prednisone Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR undergo IFRT approximately 3 weeks after the last day of ABVE course 4. Arm III (RER with CR [ABVE-PC]) Cyclophosphamide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR are randomized to receive no further treatment. Arm III (RER with CR [ABVE-PC]) Doxorubicin Hydrochloride Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR are randomized to receive no further treatment. Arm III (RER with CR [ABVE-PC]) Prednisone Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR are randomized to receive no further treatment. Arm III (RER with CR [ABVE-PC]) Etoposide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR are randomized to receive no further treatment. Arm IV (RER with less than CR [ABVE-PC, IFRT]) Cyclophosphamide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with VGPR, PR or SD undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week. Arm IV (RER with less than CR [ABVE-PC, IFRT]) Doxorubicin Hydrochloride Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with VGPR, PR or SD undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week. Arm IV (RER with less than CR [ABVE-PC, IFRT]) Etoposide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with VGPR, PR or SD undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week. Arm IV (RER with less than CR [ABVE-PC, IFRT]) Prednisone Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with VGPR, PR or SD undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week. Arm V (RER with PD) Doxorubicin Hydrochloride Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients with PD are taken off therapy. Arm V (RER with PD) Etoposide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients with PD are taken off therapy. Arm V (RER with PD) Cyclophosphamide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients with PD are taken off therapy. Arm V (RER with PD) Prednisone Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients with PD are taken off therapy. Arm VI (SER [DECA, ABVE-PC, IFRT]) Cisplatin Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VI (SER [DECA, ABVE-PC, IFRT]) Cyclophosphamide Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VI (SER [DECA, ABVE-PC, IFRT]) Cytarabine Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VI (SER [DECA, ABVE-PC, IFRT]) Doxorubicin Hydrochloride Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VI (SER [DECA, ABVE-PC, IFRT]) Etoposide Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VI (SER [DECA, ABVE-PC, IFRT]) Dexamethasone Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VI (SER [DECA, ABVE-PC, IFRT]) Prednisone Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VII (SER [ABVE-PC, IFRT]) Doxorubicin Hydrochloride Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive 2 additional courses of ABVE-PC. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VII (SER [ABVE-PC, IFRT]) Cyclophosphamide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive 2 additional courses of ABVE-PC. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VII (SER [ABVE-PC, IFRT]) Etoposide Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive 2 additional courses of ABVE-PC. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy. Arm VII (SER [ABVE-PC, IFRT]) Prednisone Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive 2 additional courses of ABVE-PC. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy.
- Primary Outcome Measures
Name Time Method Event-free Survival 5 years Probability of event-Free survival which is defined as the time from study entry to treatment failure (disease progression, disease recurrence, biopsy positive residual after completion of all protocol therapy), occurrence of a second malignant neoplasm, or death from any cause. Patients without report of such events where censored at last contact.
- Secondary Outcome Measures
Name Time Method Disease Response Assessed by Modified RECIST Criteria Protocol therapy: the overall duration of which is: (n=1527) an average of 137.1 days, median 133.0 days, interquartile range: 101.0, 164.0 days. Number of participants with complete response and very good partial response at the end of protocol therapy.
Grade 3 or 4 Non-hematologic Toxicity Protocol therapy: the overall duration of which is: (n=1684) an average of 137.3 days, median 133.0 days, interquartile range: 101.0, 164.0 days. Occurrence of any grade 4 non-hematologic toxicity or grade 3 non-hematologic toxicity which doesn't respond to treatment within 7 days despite recommended therapy modification, or toxic death, which is any death primarily attributable to treatment. Grade 3 is defined to be severe or medically significant but not immediate life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 refers to toxicities with life-threatening consequences; urgent intervention indicated.
Overall Survival 5 years Probability of overall survival which is defined as the time from study entry to death from any cause. Patients alive where censored at last contact.
Trial Locations
- Locations (175)
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Saint Luke's Mountain States Tumor Institute
🇺🇸Boise, Idaho, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Nevada Cancer Research Foundation CCOP
🇺🇸Las Vegas, Nevada, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Baptist Hospital of Miami
🇺🇸Miami, Florida, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Georgia Regents University Medical Center
🇺🇸Augusta, Georgia, United States
Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Brooklyn Hospital Center
🇺🇸Brooklyn, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Mission Hospital-Memorial Campus
🇺🇸Asheville, North Carolina, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, 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
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Women's and Children's Hospital-Adelaide
🇦🇺North Adelaide, South Australia, Australia
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Schneider Children's Medical Center of Israel
🇮🇱Petah Tikua, Israel
Starship Children's Hospital
🇳🇿Grafton, Auckland, New Zealand
San Jorge Children's Hospital
🇵🇷San Juan, Puerto Rico
Swiss Pediatric Oncology Group - Geneva
🇨ðŸ‡Geneva, Switzerland
Sanford Medical Center-Fargo
🇺🇸Fargo, North Dakota, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, 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's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Santa Barbara Cottage Hospital
🇺🇸Santa Barbara, California, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Cardinal Glennon Children's Medical Center
🇺🇸Saint Louis, Missouri, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
University of Rochester
🇺🇸Rochester, New York, United States
Weill Medical College of Cornell University
🇺🇸New York, New York, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Columbia University/Herbert Irving Cancer Center
🇺🇸New York, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Natalie Warren Bryant Cancer Center at Saint Francis
🇺🇸Tulsa, Oklahoma, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Greenville Cancer Treatment Center
🇺🇸Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
T C Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Texas Tech University Health Science Center-Amarillo
🇺🇸Amarillo, Texas, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, 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
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Childrens Hospital-King's Daughters
🇺🇸Norfolk, Virginia, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
West Virginia University Charleston
🇺🇸Charleston, West Virginia, United States
Janeway Child Health Centre
🇨🇦Saint John's, Newfoundland and Labrador, Canada
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Chedoke Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Naval Medical Center - Portsmouth
🇺🇸Portsmouth, Virginia, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
The Toledo Hospital/Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
University of Missouri - Ellis Fischel
🇺🇸Columbia, Missouri, United States
Kalamazoo Center for Medical Studies
🇺🇸Kalamazoo, Michigan, United States
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Michigan State University Clinical Center
🇺🇸East Lansing, Michigan, United States
University of Vermont College of Medicine
🇺🇸Burlington, Vermont, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
William Beaumont Hospital-Royal Oak
🇺🇸Royal Oak, Michigan, United States
New York Medical College
🇺🇸Valhalla, New York, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸Tacoma, Washington, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Carilion Clinic Children's Hospital
🇺🇸Roanoke, Virginia, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
Saint Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
The Childrens Mercy Hospital
🇺🇸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
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Florida
🇺🇸Gainesville, Florida, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States