Comparison of Different Combination Chemotherapy Regimens in Treating Children With Acute Lymphoblastic Leukemia
- Conditions
- Leukemia
- Interventions
- Registration Number
- NCT00005945
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating childhood acute lymphoblastic leukemia.
PURPOSE: This randomized phase III trial is comparing different combination chemotherapy regimens to see how well they work in treating children with acute lymphoblastic leukemia.
- Detailed Description
OBJECTIVES:
* Compare the event-free survival and overall survival of children with standard-risk acute lymphoblastic leukemia treated with escalating-dose IV methotrexate without leucovorin calcium versus oral methotrexate during the interim maintenance phase of therapy.
* Compare the event-free survival and overall survival of these patients after receiving treatment in two delayed intensification phases versus one delayed intensification phase.
* Compare the toxic effects of oral versus escalating-dose intravenous methotrexate in these patients.
* Determine the prognostic significance of the rate of disappearance of peripheral lymphoblasts and lymphocytes during the first week of treatment in these patients.
* Determine the prognostic significance of trisomies of chromosomes 4, 5, 10, and 17 and early treatment response in patients treated with these regimens.
* Determine the prognostic significance of the TEL-AML1 fusion transcript and early treatment response in patients treated with these regimens.
* Determine the minimal residual disease (MRD) by polymerase chain reaction in bone marrow and cerebrospinal fluid at various stages of therapy in these patients.
* Determine the prognostic significance of MRD during various stages of therapy in these patients.
* Determine whether a second delayed intensification therapy improves the prognosis of patients who have MRD at the end of induction therapy.
OUTLINE: This is a randomized, multicenter study. Patients without CNS disease at diagnosis, achieving a specified early marrow response profile and M1 marrow status of less than 5% blasts in the bone marrow (regardless of the proportion of mature lymphocytes) by day 28 of induction therapy, and remaining event free with favorable bone marrow status and cytogenetics between day 21 and 28 of consolidation therapy are randomized to one of four treatment arms. Patients with CNS disease at diagnosis are assigned to treatment arm II and undergo cranial irradiation. Patients with any of the following unfavorable bone marrow features and/or unfavorable cytogenetic features are assigned to the augmented treatment regimen by day 21 of induction chemotherapy or at the beginning of consolidation chemotherapy:
NOTE: All T-cell precursor patients that are not more than 4 months past completion of the delayed intensification phase of therapy should be switched to the augmented regimen as of 3/8/2004. These patients may be switched to the augmented regimen. The protocol gives specific instructions according to the phase of therapy the patients are actually in.
* Unfavorable marrow status:
* M2: 5-25% blasts in bone marrow at day 28 of induction chemotherapy (or at day 14 of induction chemotherapy if day 7 status is M3) OR
* M3: More than 25% blast cell in bone marrow, regardless of the proportion of mature lymphocytes at day 14 of induction chemotherapy
* Unfavorable cytogenetics: Must have 1 of the following:
* t(9;22)(q34;q11)
* t(4;11)(q21;q23)
* Balanced t(1;19)(q23;p13)
* Hypodiploidy with less than 45 chromosomes
* Other 11q23 translocations involving MLL Patients receive standard induction chemotherapy comprising cytarabine (ARA-C) intrathecally (IT) on day 0 or up to 72 hours before day 0; oral dexamethasone (DM) twice daily on days 0-27; vincristine (VCR) IV on days 0, 7, 14, and 21; and pegaspargase (PEG-ASP) intramuscularly (IM) once between days 3-5. Patients without CNS disease at diagnosis receive methotrexate (MTX) IT on days 7 and 28. Patients with CNS disease at diagnosis receive MTX IT on days 7, 14, 21, and 28.
Patients who have achieved M1 marrow status by day 28 of induction therapy and have favorable early bone marrow response and cytogenetics proceed to standard consolidation therapy once blood counts have recovered. Patients with M3 bone marrow status at day 28 of induction therapy are taken off the protocol. All other patients are assigned to the augmented treatment regimen.
Beginning on day 28 of induction chemotherapy, patients receive standard consolidation chemotherapy comprising VCR IV on day 0 and oral mercaptopurine (MP) on days 0-27. Patients without CNS disease at diagnosis receive MTX IT on days 7, 14, 21, and 28. Patients with CNS disease at diagnosis receive MTX IT on day 7 and cranial irradiation 5 days a week for 2 weeks. Patients with testicular disease receive bilateral testicular radiotherapy 5 days a week for 1 week and then for 3 consecutive days during the next week.
NOTE: As of 3/8/2004, patients with T-cell disease who did not achieve M1 marrow status by day 14 of induction OR who did not receive augmented induction and/or consolidation (regardless of early marrow status) receive cranial irradiation.
* Arm I: Beginning on day 28 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising oral DM twice daily on days 0-4 and 28-32; VCR IV on days 0 and 28; oral MTX on days 0, 7, 14, 21, 28, 35, 42, and 49; oral MP on days 0-49; and MTX IT on day 28.
Beginning on day 56 of interim maintenance I chemotherapy, patients receive delayed intensification chemotherapy comprising oral DM twice daily on days 0-6 and 14-20; VCR IV and doxorubicin (DOX) IV over 15 minutes to 2 hours on days 0, 7, and 14; PEG-ASP IM on day 3; cyclophosphamide (CTX) IV over 20-30 minutes on day 28; oral thioguanine (TG) on days 28-41; ARA-C IV or subcutaneously (SC) daily on days 28-31 and 35-38; and MTX IT on days 0 and 28.
Beginning on day 56 of delayed intensification chemotherapy, patients receive interim maintenance II chemotherapy identical to interim maintenance I chemotherapy except patients receive MTX IT on days 0 and 28.
Beginning on day 56 of interim maintenance II chemotherapy, patients receive maintenance chemotherapy comprising oral DM twice daily on days 0-4, 28-32, and 56-60; VCR IV on days 0, 28, and 56; oral MP on days 0-83; oral MTX on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; and MTX IT on day 0.
* Arm II: Patients receive interim maintenance I chemotherapy, delayed intensification chemotherapy, and interim maintenance II chemotherapy as in arm I. Beginning on day 56 of interim maintenance II chemotherapy, patients then receive a second course of delayed intensification chemotherapy followed by maintenance chemotherapy as in arm I.
* Arm III: Beginning on day 28 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising VCR IV; escalating doses of MTX IV on days 0, 10, 20, 30, and 40; and MTX IT on day 30. Patients then receive delayed intensification chemotherapy as in arm I. Patients receive interim maintenance II chemotherapy as in interim maintenance I chemotherapy, but with IV MTX starting at 2/3 of the maximum tolerated dose (MTD) attained in interim maintenance I chemotherapy. Patients then receive maintenance chemotherapy as in arm I.
* Arm IV: Patients receive interim maintenance I chemotherapy as in arm III, delayed intensification chemotherapy as in arm I, interim maintenance II chemotherapy as in arm III, delayed intensification II chemotherapy as in arm II, and maintenance chemotherapy as in arm I.
* Augmented Treatment: Patients receive induction chemotherapy comprising daunorubicin IV continuously for 48 hours beginning no later than day 21; oral DM twice daily on days 14-27; and VCR IV on days 14 and 21. Patients without CNS disease at diagnosis receive MTX IT on days 21 and 35. Patients with CNS disease at diagnosis receive MTX IT on days 21 and 28.
NOTE: Patients with T-cell disease should re-start with augmented consolidation and proceed as per the augmented regimen.
Beginning on day 35 of induction chemotherapy, patients receive consolidation therapy comprising CTX IV over 20-30 minutes on days 0 and 28; oral MP on days 0-13 and 28-41; ARA-C IV or SC daily on days 0-3, 7-10, 28-31, and 35-38; VCR IV on days 14, 21, 42, and 49; and PEG-ASP IM on days 14 and 42. Patients without CNS disease at diagnosis receive MTX IT on days 7, 14, and 21. Patients with CNS disease at diagnosis receive MTX IT on day 7 and cranial irradiation as in the randomized treatment section. Patients with testicular leukemia receive radiotherapy as in the randomized treatment section.
Beginning on day 63 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising VCR IV on days 0, 10, 20, 30, and 40; escalating doses of MTX IV on days 10, 20, 30, and 40; PEG-ASP IM on days 1 and 21; and MTX IT on days 0 and 30.
Beginning on day 56 of interim maintenance I chemotherapy, patients receive delayed intensification I chemotherapy comprising oral DM twice daily on days 0-6 and 14-20; VCR IV on days 0, 7, 14, 42, and 49; DOX IV over 15 minutes to 2 hours on days 0, 7, and 14; PEG-ASP IM on days 3 and 42; CTX IV over 20-30 minutes on day 28; oral TG on days 28-41; ARA-C IV or SC daily on days 28-31 and 35-38; and MTX IT on days 0 and 28.
NOTE: Patients with T-cell disease who are in interim maintenance I chemotherapy with escalating IV methotrexate should continue this phase and then proceed as per the augmented regimen. If these patients are receiving conventional interim maintenance chemotherapy with oral methotrexate, they should stop and restart the interim maintenance as per the augmented regimen. These patients receive cranial irradiation starting on day 28 of delayed intensification II chemotherapy.
Beginning on day 56 of delayed intensification I chemotherapy, patients receive interim maintenance II chemotherapy as in interim maintenance I chemotherapy, but with IV MTX starting at 2/3 of the MTD attained in interim maintenance I chemotherapy.
NOTE: Patients with T-cell disease who are in delayed intensification I chemotherapy proceed with this phase, with the addition of 2 vincristine doses on days 42 and 49 and PEG-ASP on day 42. These patients then proceed as per the augmented regimen with the addition of cranial irradiation starting on day 28 of delayed intensification II chemotherapy.
NOTE: Patients with T-cell disease who are within 4 months of completing delayed intensification I chemotherapy and have not received interim maintenance II chemotherapy with escalating IV methotrexate or delayed intensification II chemotherapy receive a course of interim maintenance chemotherapy and delayed intensification II chemotherapy according to the augmented regimen. If these patients have received interim maintenance II chemotherapy with escalating IV methotrexate, they receive delayed intensification II chemotherapy according to the augmented regimen. These patients also receive cranial irradiation starting on day 28 of delayed intensification II chemotherapy and then proceed to maintenance therapy.
Beginning on day 56 of interim maintenance II chemotherapy, patients receive delayed intensification II chemotherapy as in delayed intensification I chemotherapy.
Beginning on day 56 of delayed intensification II chemotherapy, patients receive maintenance chemotherapy comprising oral DM twice daily on days 0-4, 28-32, and 56-60; VCR IV on days 0, 28, and 56; oral MP on days 0-83; oral MTX on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; and MTX IT on day 0.
Patients are followed every 4-8 weeks for one year, every 3 months for one year, every 6 months for one year, and then annually thereafter.
PROJECTED ACCRUAL: A total of 2,037 randomized patients will be accrued for this study within 3.75 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3054
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Induction and Oral MTX, Single Delayed Intensification vincristine sulfate Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction Not Randomized vincristine sulfate Standard Induction (28 Days). M3 Marrow at Day 28 and Off Protocol Therapy. Induction and Augmented regimen (IV MTX, Double DI) vincristine sulfate Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Augmented regimen (IV MTX, Double DI) radiation therapy Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Oral MTX, Double Delayed Intensification CNS vincristine sulfate Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase. Induction and Oral MTX, Double Delayed Intensification CNS radiation therapy Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase. Induction and Augmented regimen (IV MTX, Double DI) daunorubicin hydrochloride Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Oral MTX, Single Delayed Intensification radiation therapy Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Double Delayed Intensification vincristine sulfate Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Double Delayed Intensification radiation therapy Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Double Delayed Intensification radiation therapy Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Single Delayed Intensification vincristine sulfate Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Double Delayed Intensification vincristine sulfate Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Single Delayed Intensification radiation therapy Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction Not Randomized cyclophosphamide Standard Induction (28 Days). M3 Marrow at Day 28 and Off Protocol Therapy. Induction Not Randomized methotrexate Standard Induction (28 Days). M3 Marrow at Day 28 and Off Protocol Therapy. Induction Not Randomized dexamethasone Standard Induction (28 Days). M3 Marrow at Day 28 and Off Protocol Therapy. Induction Not Randomized pegaspargase Standard Induction (28 Days). M3 Marrow at Day 28 and Off Protocol Therapy. Induction and Oral MTX, Double Delayed Intensification CNS cyclophosphamide Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase. Induction and Oral MTX, Double Delayed Intensification CNS cytarabine Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase. Induction and Oral MTX, Double Delayed Intensification CNS dexamethasone Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase. Induction and Oral MTX, Double Delayed Intensification CNS doxorubicin hydrochloride Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase. Induction and Oral MTX, Double Delayed Intensification CNS mercaptopurine Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase. Induction and Oral MTX, Double Delayed Intensification CNS pegaspargase Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase. Induction and Oral MTX, Double Delayed Intensification CNS thioguanine Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase. Induction and Oral MTX, Double Delayed Intensification CNS methotrexate Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase. Induction and Augmented regimen (IV MTX, Double DI) cyclophosphamide Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Augmented regimen (IV MTX, Double DI) cytarabine Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Augmented regimen (IV MTX, Double DI) dexamethasone Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Augmented regimen (IV MTX, Double DI) doxorubicin hydrochloride Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Augmented regimen (IV MTX, Double DI) pegaspargase Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Augmented regimen (IV MTX, Double DI) mercaptopurine Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Augmented regimen (IV MTX, Double DI) methotrexate Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Augmented regimen (IV MTX, Double DI) thioguanine Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses). Induction and Oral MTX, Single Delayed Intensification cytarabine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Single Delayed Intensification cyclophosphamide Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Single Delayed Intensification methotrexate Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Single Delayed Intensification dexamethasone Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Single Delayed Intensification doxorubicin hydrochloride Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Single Delayed Intensification thioguanine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Single Delayed Intensification mercaptopurine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Single Delayed Intensification pegaspargase Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Double Delayed Intensification cytarabine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Double Delayed Intensification cyclophosphamide Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Double Delayed Intensification dexamethasone Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Double Delayed Intensification doxorubicin hydrochloride Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Double Delayed Intensification mercaptopurine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Double Delayed Intensification methotrexate Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Double Delayed Intensification thioguanine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and Oral MTX, Double Delayed Intensification pegaspargase Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Single Delayed Intensification cyclophosphamide Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Single Delayed Intensification cytarabine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Single Delayed Intensification doxorubicin hydrochloride Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Single Delayed Intensification dexamethasone Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Single Delayed Intensification methotrexate Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Single Delayed Intensification mercaptopurine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Single Delayed Intensification pegaspargase Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Single Delayed Intensification thioguanine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Double Delayed Intensification cyclophosphamide Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Double Delayed Intensification cytarabine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Double Delayed Intensification dexamethasone Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Double Delayed Intensification doxorubicin hydrochloride Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Double Delayed Intensification mercaptopurine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Double Delayed Intensification pegaspargase Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Double Delayed Intensification methotrexate Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase. Induction and IV MTX, Double Delayed Intensification thioguanine Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.
- Primary Outcome Measures
Name Time Method Event Free Survival Time of randomization The primary outcome index used in examining the randomized treatment groups will be event free survival (EFS) from the time of randomization (i.e., end of Consolidation), where the life table events will consist of the first occurrence of leukemic relapse at any site, death, or occurrence of a second malignancy.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (130)
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
MD Anderson Cancer Center at University of Texas
🇺🇸Houston, Texas, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Riley Children Cancer Center at Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Children's Hospitals and Clinics - Minneapolis/St. Paul
🇺🇸Minneapolis, Minnesota, United States
Methodist Cancer Center at Methodist Specialty and Transplant Hospital
🇺🇸San Antonio, Texas, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Jonsson Comprehensive Cancer Center, UCLA
🇺🇸Los Angeles, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Children's Hospital and Research Center at Oakland
🇺🇸Oakland, California, United States
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
🇺🇸Orange, California, United States
Santa Barbara Cottage Hospital
🇺🇸Santa Barbara, California, United States
Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego
🇺🇸San Diego, California, United States
UCSF Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
General Robert Huyser Cancer Center at David Grant Medical Center
🇺🇸Travis Air Force Base, California, United States
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Lombardi Cancer Center at Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
🇺🇸Atlanta, Georgia, United States
Medical Center of Central Georgia
🇺🇸Macon, Georgia, United States
Mountain States Tumor Institute - Boise
🇺🇸Boise, Idaho, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Lutheran General Cancer Care Center
🇺🇸Park Ridge, Illinois, United States
University of Illinois Medical Center
🇺🇸Chicago, Illinois, United States
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
Breslin Cancer Center at Ingham Regional Medical Center
🇺🇸Lansing, Michigan, United States
St. Joseph's Hospital and Medical Center
🇺🇸Paterson, New Jersey, United States
Brooklyn Hospital Center
🇺🇸Brooklyn, New York, United States
Cancer Center of Albany Medical Center
🇺🇸Albany, New York, United States
SUNY Downstate Medical Center
🇺🇸Brooklyn, New York, United States
Schneider Children's Hospital
🇺🇸New Hyde Park, New York, United States
Brookdale University Hospital and Medical Center
🇺🇸Brooklyn, New York, United States
Comprehensive Cancer Center at Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
New York Weill Cornell Cancer Center at Cornell University
🇺🇸New York, New York, United States
Herbert Irving Comprehensive Cancer Center at Columbia University
🇺🇸New York, New York, United States
Long Island Cancer Center at Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Group Health Central Hospital
🇺🇸Seattle, Washington, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
Vanderbilt Children's Hospital
🇺🇸Nashville, Tennessee, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Children's Hospital of Austin
🇺🇸Austin, Texas, United States
St. Mary's - Duluth Clinic Cancer Center
🇺🇸Duluth, Minnesota, United States
Dakota Cancer Institute at Innovis Health - Dakota Clinic
🇺🇸Fargo, North Dakota, United States
University of Minnesota Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Meritcare Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Valerie Fund Children's Center at Atlantic Health
🇺🇸Summit, New Jersey, United States
William Beaumont Hospital - Royal Oak
🇺🇸Royal Oak, Michigan, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
🇺🇸Baltimore, Maryland, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
CCOP - Marshfield Clinic Research Foundation
🇺🇸Marshfield, Wisconsin, United States
Allan Blair Cancer Centre at Pasqua Hospital
🇨🇦Regina, Saskatchewan, Canada
CCOP - Beaumont
🇺🇸Royal Oak, Michigan, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Royal Children's Hospital
🇦🇺Brisbane, Queensland, Australia
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Baystate Regional Cancer Program at D'Amour Center for Cancer Care
🇺🇸Springfield, Massachusetts, United States
St. Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Swiss Pediatric Oncology Group Lausanne
🇨ðŸ‡Lausanne, Switzerland
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
Children's Hospital of Western Ontario
🇨🇦London, Ontario, Canada
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Children's Hospital Cancer Center
🇺🇸Denver, Colorado, United States
Josephine Ford Cancer Center at Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Presbyterian - St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Children's Hospital of Omaha
🇺🇸Omaha, Nebraska, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
East Tennessee State University Cancer Center at Johnson City Medical Center
🇺🇸Johnson City, Tennessee, United States
Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Columbus Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Doernbecher Children's Hospital at Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Children's Hospital at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
St. Vincent Mercy Medical Center
🇺🇸Toledo, Ohio, United States
MBCCOP - South Texas Pediatrics
🇺🇸San Antonio, Texas, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
CCOP - Columbia River Oncology Program
🇺🇸Portland, Oregon, United States
Sydney Children's Hospital
🇦🇺Randwick, New South Wales, Australia
Janeway Children's Health and Rehabilitation Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
Children's Medical Center - Dayton
🇺🇸Dayton, Ohio, United States
Sioux Valley Hospital and University of South Dakota Medical Center
🇺🇸Sioux Falls, South Dakota, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸Tacoma, Washington, United States
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
🇺🇸Charleston, West Virginia, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Cabell Huntington Hospital
🇺🇸Huntington, West Virginia, United States
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Deaconess Medical Center
🇺🇸Spokane, Washington, United States
Swiss Pediatric Oncology Group Bern
🇨ðŸ‡Bern, Switzerland
CCOP - Scott and White Hospital
🇺🇸Temple, Texas, United States
Texas Tech University Health Sciences Center School of Medicine
🇺🇸Amarillo, Texas, United States
Children's Hospital of the King's Daughters
🇺🇸Norfolk, Virginia, United States
Starship Children's Health
🇳🇿Auckland, New Zealand
Swiss Pediatric Oncology Group Geneva
🇨ðŸ‡Geneva, Switzerland
Bellin Memorial Hospital
🇺🇸Green Bay, Wisconsin, United States
Kaiser Permanente Medical Center - Sacramento
🇺🇸Sacramento, California, United States
Yale Comprehensive Cancer Center
🇺🇸New Haven, Connecticut, United States
Markey Cancer Center at University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
MBCCOP - LSU Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Blumenthal Cancer Center at Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Kaiser Permanente Medical Center - Santa Clara
🇺🇸Santa Clara, California, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States