Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System With Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Children's Oncology Group
- Enrollment
- 70
- Locations
- 94
- Primary Endpoint
- Event-free Survival
Study Overview
Brief Summary
This phase III trial studies the side effects of combination chemotherapy, 3-dimensional conformal radiation therapy, and an autologous peripheral blood stem cell transplant, and to see how well they work in treating young patients with atypical teratoid/rhabdoid tumor of the central nervous system. Giving high-dose chemotherapy before an autologous peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy or radiation therapy.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the 6-, 12-, and 24-month event-free survival and overall survival of children (birth to 21 years of age) with atypical teratoid/rhabdoid CNS tumors (AT/RT), diagnosed based on histology, immunophenotyping, and modern molecular and immunohistochemical analysis of INI1, treated with surgery, intensive chemotherapy combined with stem cell rescue, and radiation therapy.
II. To compare the outcome of very young patients (under 3 years old) on this study whose histologic diagnosis is AT/RT with infants identified as having AT/RT on POG-9233 and CCG-9921.
SECONDARY OBJECTIVES:
I. To determine the feasibility and toxicity of the proposed chemotherapy regimen in combination with radiation therapy.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 21 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of CNS atypical teratoid/rhabdoid tumor (AT/RT) or tumors that have a mutation of the INI1 gene (even if the tumor does not have the usual histologic characteristics of AT/RT)
- •Patients with extra neural metastasis (M4) or renal rhabdoid tumors are not eligible
- •Patients with MRI evidence of spinal disease are eligible
- •Must have undergone definitive surgery in the past 31 days
- •Cranial MRI (with and without gadolinium) must be done pre-operatively
- •Post-operatively, cranial MRI (with and without gadolinium) must be done, preferably within 48 hours of surgery or 10-28 days after surgery
- •Entire spinal MRI must be obtained either pre-operatively (with gadolinium) or post-operatively (10-28 days after surgery), prior to study enrollment (with and without gadolinium)
- •Life expectancy > 8 weeks
- •ANC > 1,000/uL
- •Platelet count > 100,000/uL (transfusion independent)
- •Hemoglobin > 8 g/dL (RBC transfusions allowed)
- •Creatinine clearance (minimum of 12-24 hour urine collection) or radioisotope GFR >= 60 mL/min
- •Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
- •AST and ALT < 2 times ULN for age
- •Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 47% by radionuclide angiogram
- •No evidence of dyspnea at rest
- •Pulse oximetry > 94% on room air
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No prior radiotherapy or chemotherapy except for the following:
- •Patients enrolled on protocol ACNS0334 whose tumors demonstrate the INI1 gene mutation are eligible to transfer to this study even if they have received one course of induction therapy (these patients must be re-consented to treatment and restaged)
- •Prior corticosteroids allowed
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: 3-Dimensional Conformal Radiation Therapy (Radiation)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Carboplatin (Drug)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Cisplatin (Drug)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Cyclophosphamide (Drug)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Etoposide (Drug)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Filgrastim (Biological)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Laboratory Biomarker Analysis (Other)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Leucovorin Calcium (Drug)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Methotrexate (Drug)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Thiotepa (Drug)
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
Intervention: Vincristine Sulfate (Drug)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: 3-Dimensional Conformal Radiation Therapy (Radiation)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Carboplatin (Drug)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Cisplatin (Drug)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Cyclophosphamide (Drug)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Etoposide (Drug)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Filgrastim (Biological)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis (Other)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Leucovorin Calcium (Drug)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Methotrexate (Drug)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Thiotepa (Drug)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers.
Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Vincristine Sulfate (Drug)
Outcomes
Primary Outcomes
Event-free Survival
Time Frame: Up to 4 years after study enrollment
Estimated 4-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.
Overall Survival (OS)
Time Frame: Up to 4 years after study enrollment
Estimated 4-year survival, where survival is calculated as the time from study enrollment to death from any cause or last follow-up alive whichever occurs first. Kaplan-Meier method is used for estimation. Patients alive at last contact are censored.
Toxic Death
Time Frame: During and after completion of study treatment up to 1 year after enrollment.
The number of patients who experience death that is considered to be primarily attributable to complications of treatment.
Secondary Outcomes
- Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy(During protocol therapy up to 1 year after enrollment.)