Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
- Conditions
- Acute Lymphoblastic LeukemiaChildhood B Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT00103285
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
This randomized phase III trial is studying different combination chemotherapy regimens and comparing how well they work in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine whether the substitution of three intensified phases of post-Induction treatment for standard phases will improve the event free survival (EFS) of children with SR-average acute lymphoblastic leukemia (ALL).
II. Determine whether the substitution of intensified Consolidation for standard Consolidation will improve the EFS of children with SR-average ALL.
III. To determine whether the addition of four doses of percutaneous endoscopic gastrostomy (PEG) asparaginase, given once every three weeks during Consolidation and Interim Maintenance phases, will improve the EFS for children with SR-low ALL.
SECONDARY OBJECTIVES:
I. Identify potentially modifiable factors associated with impaired health related quality of life (HRQOL) at different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL study.
II. Determine the critical time periods when future intervention studies to mitigate adverse HRQOL outcomes should occur.
III. Correlate day 29 minimal residual disease (MRD) with EFS and overall survival (OS) of patients treated with these regimens.
IV. Correlate early marrow response with day 29 MRD status. V. To improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster (BFM).
VI. To examine the relative contributions of genetic factors and early treatment response to outcome by comparing the outcome of patients with and without TEL-AML1 fusion or triple trisomy and low levels of MRD at end Induction who are treated with identical therapy on the standard arms of the SR-low and SR-average trials.
OUTLINE: This is a 2-part, partially randomized, multicenter study. Patients are stratified according to early response to study induction therapy (rapid early response \[standard risk (SR)-low or SR-average acute lymphoblastic leukemia (ALL)\] vs slow early response \[SR-high ALL\]). After completion of induction therapy but before proceeding to part II therapy, patients are assigned to 1 of 3 groups based on stratification.
PART I:
INDUCTION THERAPY: All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) \< 0.1% OR MRD \>= 0.1% and \< 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD \>= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study.
EXTENDED INDUCTION THERAPY: Patients receive dexamethasone IV or PO BID on days 1-14; vincristine IV on days 1 and 8; pegaspargase IM on day 4, 5, or 6; and daunorubicin hydrochloride IV over 15 minutes to 2 hours on day 1. Patients with M1 bone marrow and MRD \< 1% after extended induction therapy proceed to therapy in part II. Patients with M2 or M3 bone marrow after extended induction therapy are removed from the study.
PART II:
GROUP 1 (SR-low ALL): Patients are randomized to 1 of 2 treatment arms.
ARM I:
STANDARD CONSOLIDATION THERAPY: Patients receive vincristine IV on day 1; mercaptopurine PO on days 1-28; and methotrexate IT on days 1, 8, and 15. Patients with Down syndrome (DS) receive leucovorin calcium (PO) at 48 and 60 hours after each dose of methotrexate IT.
STANDARD INTERIM MAINTENANCE THERAPY: Patients receive vincristine IV on days 1 and 29; dexamethasone IV or PO BID on days 1-5 and 29-33; mercaptopurine PO on days 1-50; methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, and 50; and methotrexate IT on day 29. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT.
STANDARD DELAYED INTENSIFICATION (DI) THERAPY: Patients receive vincristine IV on days 1, 8, and 15; dexamethasone IV or PO BID on days 1-21; doxorubicin hydrochloride IV over 15 minutes to 2 hours on days 1, 8, and 15; pegaspargase IM on day 4, 5, or 6; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or subcutaneously (SC) on days 29-32 and 36-39; thioguanine PO on days 29-42; and methotrexate IT on days 1 and 29. Patients with DS receive dexamethasone IV or PO BID on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT.
ARM II:
EXPERIMENTAL CONSOLIDATION THERAPY: Patients receive vincristine, mercaptopurine, methotrexate, and leucovorin calcium as in arm I and pegaspargase IM on days 1 and 22.
EXPERIMENTAL INTERIM MAINTENANCE THERAPY: Patients receive vincristine, dexamethasone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm I and pegaspargase IM on days 15 and 36.Standard DI therapy: Patients receive standard DI therapy as in arm I.
GROUP 2 (SR-average ALL): Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I.
ARM II:
STANDARD CONSOLIDATION THERAPY: Patients receive standard consolidation therapy as in group 1, arm I. Augmented interim maintenance therapy: Patients receive vincristine IV and methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase IM on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Augmented DI therapy: Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21; doxorubicin hydrochloride IV over 15 minutes to 2 hours on days 1, 8, and 15; pegaspargase IM on day 4, 5, or 6 AND day 43; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or SC on days 29-32 and 36-39; thioguanine PO on days 29-42; and methotrexate IT on days 1, 29, and 36. Patients with DS receive dexamethasone on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT.
ARM III:
INTENSIFIED CONSOLIDATION THERAPY: Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; pegaspargase IM on days 15 and 43; and methotrexate IT on days 1, 8, 15\*, and 22\*. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT\*.
NOTE: \*Patients with CNS3 disease at diagnosis do not receive methotrexate on days 15 and 22 or leucovorin calcium.
STANDARD INTERIM MAINTENANCE THERAPY: Patients receive standard interim maintenance therapy as in group 1, arm I.
STANDARD DI THERAPY: Patients receive standard DI therapy as in group 1, arm I.
ARM IV:
INTENSIFIED CONSOLIDATION THERAPY: Patients receive intensified consolidation therapy as in group 2, arm III.
AUGMENTED INTERIM MAINTENANCE THERAPY: Patients receive augmented interim maintenance therapy as in group 2, arm II.
AUGMENTED DI THERAPY: Patients receive augmented DI therapy as in group 2, arm II.
GROUP 3 (SR-high ALL): Patients receive the following therapy: Intensified consolidation therapy: Patients receive intensified consolidation therapy as in group 2, arm III.
AUGMENTED INTERIM MAINTENANCE\* THERAPY: Patients receive augmented interim maintenance therapy as in group 2, arm II. Treatment repeats every 56 days for 2 courses.
NOTE: \*As of Amendment #7, all SR-High patients currently receiving AIM 1 therapy should complete this phase of therapy and proceed to ADI 1 therapy as originally planned including Capizzi methotrexate during AIM 1. Upon completion of ADI 1, patients should receive a second Interim Maintenance phase with high-dose methotrexate (IM HD) rather than Capizzi methotrexate. Patients should then proceed to ADI 2 and then Maintenance.
AUGMENTED DI\* THERAPY: Patients receive augmented DI therapy as in group 2, arm II. Treatment repeats every 56 days for 2 courses\*\*.
NOTE: \*As of Amendment #7, all SR-High patients currently receiving ADI 1 therapy should complete this phase of therapy as originally planned. Upon completion of ADI 1, patients should receive a second Interim Maintenance phase with IM HD. Patients should then proceed to ADI 2 and then Maintenance.
NOTE: \*\*Patients with CNS3 disease at diagnosis also undergo cranial radiotherapy on days 29-33 and 36-40 during course 2 only; these patients do not receive methotrexate on day 36, thioguanine, or leucovorin calcium.
MAINTENANCE THERAPY: All patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily on days 1-5, 29-33, and 57-61; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and methotrexate IT\* on day 1. Courses repeat every 84 days for a total of 2 years from the start of interim maintenance therapy for female patients and 3 years from the start of interim maintenance therapy for male patients.
NOTE: \*SR-High or CNS3 patients should receive up to a maximum of 23 intrathecal treatments for females and 26 intrathecal treatments for males.
After the completion of study treatment, patients are followed every 1-2 months for 2 years, every 3 months for 1 year, and then every 6-12 months for 2 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 5377
-
Patients must be enrolled on AALL03B1 prior to enrollment on AALL0331
-
Initial white blood cells (WBC) < 50,000/ul
-
Newly diagnosed B-precursor acute lymphoblastic leukemia
-
Standard-risk (SR) disease meeting 1 of the following criteria:
-
SR-average by age and WBC
-
No unfavorable features
-
Rapid early responder (RER) by day 15
-
CNS 1 or 2
-
Minimal residual disease (MRD) negative on day 29
-
Trisomies of 4, 10, and 17 or TEL-AML1 translocation and RER and CNS2 allowed
-
SR-low by age and WBC
-
No unfavorable features
-
RER by day 15
-
MRD negative on day 29
-
CNS1
-
Favorable cytogenetics-trisomies of 4, 10, and 17 or TEL-AML translocation
-
SR-high
-
Unfavorable features meeting ≥ 1 of the following criteria:
- MLL rearrangements and RER
- Steroid pretreatment
- CNS3
- Slow early responder by morphology or MRD
-
-
Patients with Down syndrome are allowed
-
Patients with overt testicular disease are not eligible for this study, but may be eligible for AALL0232
-
Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine; intrathecal chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; (Note: the central nervous system [CNS] status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment
-
Patients receiving prior steroid therapy may be eligible for AALL0331 study
-
Patients with a contraindication to additional asparaginase therapy, following Induction, are not eligible for the Standard Risk-Low study, and should be removed from protocol therapy at the end of Induction
-
Patients who are assigned to the standard risk-average group following Induction and who meet the HRQOL
-
Age at diagnosis >= 2 years (note that this is a more restrictive age range than for the therapeutic component of the study)
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At least one parent with reading comprehension of English or Spanish languages for which validated surveys exist
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Diagnosis at one of the institutions participating in this limited institution correlative study
-
A parent or legal guardian must sign a written informed consent/parental permission for all patients
-
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 0 Induction Therapy Leucovorin Calcium All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) \< 0.1% OR MRD \>= 0.1% and \< 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD \>= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study. Group 1-SR-low ALL, Arm I (combination chemotherapy) Leucovorin Calcium Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Group 1-SR-low ALL, Arm I (combination chemotherapy) Vincristine Sulfate Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Group 2-SR-avg ALL, arm III (combination chemotherapy) Leucovorin Calcium Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm III (combination chemotherapy) Vincristine Sulfate Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 0 Induction Therapy Vincristine Sulfate All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) \< 0.1% OR MRD \>= 0.1% and \< 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD \>= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study. Group 2-SR-avg ALL, arm IV (combination chemotherapy) 3-Dimensional Conformal Radiation Therapy Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 1-SR-low ALL, arm II (combination chemotherapy) Vincristine Sulfate Patients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm I (combination chemotherapy) 3-Dimensional Conformal Radiation Therapy Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm IV (combination chemotherapy) Leucovorin Calcium Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 1-SR-low ALL, arm II (combination chemotherapy) 3-Dimensional Conformal Radiation Therapy Patients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 1-SR-low ALL, arm II (combination chemotherapy) Leucovorin Calcium Patients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm IV (combination chemotherapy) Vincristine Sulfate Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy 3-Dimensional Conformal Radiation Therapy Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm I (combination chemotherapy) Leucovorin Calcium Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm II (combination chemotherapy) Leucovorin Calcium Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm II (combination chemotherapy) 3-Dimensional Conformal Radiation Therapy Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy Leucovorin Calcium Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm II (combination chemotherapy) Vincristine Sulfate Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm III (combination chemotherapy) 3-Dimensional Conformal Radiation Therapy Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy Vincristine Sulfate Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 0 Induction Therapy Cytarabine All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) \< 0.1% OR MRD \>= 0.1% and \< 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD \>= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study. Group 0 Induction Therapy Dexamethasone All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) \< 0.1% OR MRD \>= 0.1% and \< 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD \>= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study. Group 0 Induction Therapy Pegaspargase All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) \< 0.1% OR MRD \>= 0.1% and \< 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD \>= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study. Group 0 Induction Therapy Methotrexate All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) \< 0.1% OR MRD \>= 0.1% and \< 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD \>= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study. Group 1-SR-low ALL, Arm I (combination chemotherapy) Cyclophosphamide Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Group 1-SR-low ALL, Arm I (combination chemotherapy) Cytarabine Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Group 1-SR-low ALL, Arm I (combination chemotherapy) Dexamethasone Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Group 1-SR-low ALL, Arm I (combination chemotherapy) Pegaspargase Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Group 1-SR-low ALL, Arm I (combination chemotherapy) Doxorubicin Hydrochloride Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Group 1-SR-low ALL, Arm I (combination chemotherapy) Mercaptopurine Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Group 1-SR-low ALL, Arm I (combination chemotherapy) Methotrexate Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Group 1-SR-low ALL, Arm I (combination chemotherapy) Thioguanine Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Group 1-SR-low ALL, arm II (combination chemotherapy) Dexamethasone Patients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 1-SR-low ALL, arm II (combination chemotherapy) Mercaptopurine Patients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 1-SR-low ALL, arm II (combination chemotherapy) Methotrexate Patients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 1-SR-low ALL, arm II (combination chemotherapy) Pegaspargase Patients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm I (combination chemotherapy) Cyclophosphamide Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm I (combination chemotherapy) Cytarabine Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm I (combination chemotherapy) Dexamethasone Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm I (combination chemotherapy) Mercaptopurine Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm I (combination chemotherapy) Methotrexate Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm I (combination chemotherapy) Doxorubicin Hydrochloride Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm I (combination chemotherapy) Pegaspargase Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm I (combination chemotherapy) Thioguanine Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm II (combination chemotherapy) Cyclophosphamide Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm II (combination chemotherapy) Cytarabine Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm II (combination chemotherapy) Doxorubicin Hydrochloride Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm II (combination chemotherapy) Dexamethasone Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm II (combination chemotherapy) Methotrexate Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm II (combination chemotherapy) Pegaspargase Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm II (combination chemotherapy) Thioguanine Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm III (combination chemotherapy) Cyclophosphamide Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm III (combination chemotherapy) Dexamethasone Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm III (combination chemotherapy) Cytarabine Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm III (combination chemotherapy) Doxorubicin Hydrochloride Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm III (combination chemotherapy) Mercaptopurine Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm III (combination chemotherapy) Methotrexate Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm III (combination chemotherapy) Thioguanine Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm III (combination chemotherapy) Pegaspargase Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm IV (combination chemotherapy) Cyclophosphamide Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm IV (combination chemotherapy) Cytarabine Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm IV (combination chemotherapy) Dexamethasone Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm IV (combination chemotherapy) Doxorubicin Hydrochloride Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm IV (combination chemotherapy) Mercaptopurine Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm IV (combination chemotherapy) Methotrexate Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm IV (combination chemotherapy) Thioguanine Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 2-SR-avg ALL, arm IV (combination chemotherapy) Pegaspargase Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy Cytarabine Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy Cyclophosphamide Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy Dexamethasone Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy Mercaptopurine Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy Doxorubicin Hydrochloride Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy Methotrexate Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy Pegaspargase Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Group 3-SR-high ALL, combination chemotherapy Thioguanine Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.
- Primary Outcome Measures
Name Time Method Event-free Survival (EFS) for SR-Average ALL Patients 6 years EFS for SR-Average with standard and Intensified Consolidation. Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Event-free Survival (EFS) for SR-Low Patients 6 years Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
- Secondary Outcome Measures
Name Time Method Health-related Quality of Life Relative to Physical, Social and Emotional Impairment At 1, 6 and 12 months after diagnosis and, 3 months post-therapy To identify potentially modifiable factors associated with impaired health related quality of life (HRQOL) at different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL study.Standardized scores will be computed for child function using the gender and age-adjusted scores available from normative data from a healthy population of about 10,000 children. The various domains of family functioning will be assessed using well-validated instruments and analyzed as a dichotomous variable (impaired vs. non-impaired family functioning). Multiple regression analysis will be used to test the effect of family functioning (adjusted for therapy given, age at diagnosis, gender, socioeconomic status and other factors) on child function.
Event-Free Survival Probability According to MRD Status End Induction (Day 29) MRD at Day 29 of therapy Event-Free survival by Day 29 MRD status (negative vs positive), Event Free Probability (time from study entry to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Overall Survival Probability (OS) According to Induction Day 29 MRD Status Overall Survival Probability of 6 years Overall survival by Day 29 MRD status (negative vs positive), Overall survival defined as time from study entry to death or date of last contact for patients who are alive.
Early Marrow Status (EMS) by MRD Status End Induction (Day 29) Early Marrow Status at Day 15, MRD Status at Day 29 of therapy. Early Marrow Status defined as M1 versus M2/M3 marrow is correlated with MRD (Positive vs. Negative)
Optimal Time Point for Advance Health Related Quality of Life Intervention At 1 month after diagnosis and 3 months post-therapy. Percentage of patients with elevated Anxiety.
Event-free Survival (EFS) for SR-High Patients. 6 years Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Event-Free Survival (EFS) for Low MRD (Negative) Subjects by Genetic Subset (TEL/Trisomy Positive vs Negative) 6 years Event-free probability where EFS is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Trial Locations
- Locations (236)
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
UCLA / Jonsson Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Mattel Children's Hospital UCLA
🇺🇸Los Angeles, California, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, 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
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
USA Health Strada Patient Care Center
🇺🇸Mobile, Alabama, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Banner Children's at Desert
🇺🇸Mesa, Arizona, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Sacred Heart Hospital
🇺🇸Pensacola, Florida, United States
University of Connecticut
🇺🇸Farmington, Connecticut, United States
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Tufts Children's Hospital
🇺🇸Boston, Massachusetts, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
UMass Memorial Medical Center - University Campus
🇺🇸Worcester, Massachusetts, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Beaumont Children's Hospital-Royal Oak
🇺🇸Royal Oak, Michigan, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Saint Vincent Hospital and Health Care Center
🇺🇸Indianapolis, Indiana, United States
Michigan State University Clinical Center
🇺🇸East Lansing, Michigan, United States
Cardinal Glennon Children's Medical Center
🇺🇸Saint Louis, Missouri, United States
Kalamazoo Center for Medical Studies
🇺🇸Kalamazoo, Michigan, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Saint Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Greenville Cancer Treatment Center
🇺🇸Greenville, South Carolina, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸Green Bay, Wisconsin, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Nevada Cancer Research Foundation NCORP
🇺🇸Las Vegas, Nevada, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Carilion Children's
🇺🇸Roanoke, Virginia, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Tod Children's Hospital - Forum Health
🇺🇸Youngstown, Ohio, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Children's Oncology Group
🇺🇸Philadelphia, Pennsylvania, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
T C Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
NYU Winthrop Hospital
🇺🇸Mineola, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Swiss Pediatric Oncology Group - Lausanne
🇨🇭Lausanne, Switzerland
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Mary Bridge Children's Hospital and Health Center
🇺🇸Tacoma, Washington, United States
Children's Hospital
🇨🇦London, Ontario, Canada
Wellington Children's Hospital
🇳🇿Wellington, New Zealand
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Swiss Pediatric Oncology Group - Bern
🇨🇭Bern, Switzerland
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Swiss Pediatric Oncology Group - Geneva
🇨🇭Geneva, Switzerland
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Kingston Health Sciences Centre
🇨🇦Kingston, Ontario, Canada
Victoria Hospital
🇨🇦London, Ontario, Canada
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
UCSF Medical Center-Mount Zion
🇺🇸San Francisco, California, United States
UCSF Medical Center-Parnassus
🇺🇸San Francisco, California, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Ascension Saint John Hospital
🇺🇸Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Legacy Emanuel Children's Hospital
🇺🇸Portland, Oregon, United States
Legacy Emanuel Hospital and Health Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸Denver, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
The Montreal Children's Hospital of the MUHC
🇨🇦Montreal, Quebec, Canada
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Harbor-University of California at Los Angeles Medical Center
🇺🇸Torrance, California, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Maine Children's Cancer Program
🇺🇸Scarborough, Maine, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
William Beaumont Hospital-Royal Oak
🇺🇸Royal Oak, Michigan, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Brookdale Hospital Medical Center
🇺🇸Brooklyn, New York, United States
Brooklyn Hospital Center
🇺🇸Brooklyn, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸Toledo, Ohio, United States
Mercy Children's Hospital
🇺🇸Toledo, Ohio, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Texas Tech University Health Sciences Center-Amarillo
🇺🇸Amarillo, Texas, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
University of Vermont and State Agricultural College
🇺🇸Burlington, Vermont, United States
Naval Medical Center - Portsmouth
🇺🇸Portsmouth, Virginia, United States
Janeway Child Health Centre
🇨🇦Saint John's, Newfoundland and Labrador, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Starship Children's Hospital
🇳🇿Grafton, Auckland, New Zealand
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Santa Barbara Cottage Hospital
🇺🇸Santa Barbara, California, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸Oak Lawn, Illinois, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Columbia Regional
🇺🇸Columbia, Missouri, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
University of Missouri - Ellis Fischel
🇺🇸Columbia, Missouri, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
Mission Hospital
🇺🇸Asheville, North Carolina, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Prisma Health Richland Hospital
🇺🇸Columbia, South Carolina, United States
Royal Children's Hospital-Brisbane
🇦🇺Herston, Queensland, Australia
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
West Virginia University Charleston Division
🇺🇸Charleston, West Virginia, United States
Women's and Children's Hospital-Adelaide
🇦🇺North Adelaide, South Australia, Australia
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Natalie Warren Bryant Cancer Center at Saint Francis
🇺🇸Tulsa, Oklahoma, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Children's Mercy Hospitals and Clinics
🇺🇸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 Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Tripler Army Medical Center
🇺🇸Honolulu, Hawaii, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States