Combination Chemotherapy, Radiation Therapy, and an Autologous Peripheral Blood Stem Cell Transplant in Treating Young Patients With Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System
|ClinicalTrials.gov Identifier: NCT00653068|
Recruitment Status : Active, not recruiting
First Posted : April 4, 2008
Results First Posted : February 13, 2017
Last Update Posted : March 20, 2017
|Condition or disease||Intervention/treatment||Phase|
|Childhood Atypical Teratoid/Rhabdoid Tumor||Procedure: autologous hematopoietic stem cell transplantation Radiation: 3-dimensional conformal radiation therapy Drug: methotrexate Drug: leucovorin calcium Drug: etoposide Drug: cyclophosphamide Drug: cisplatin Biological: filgrastim Drug: carboplatin Drug: thiotepa Drug: vincristine sulfate Other: laboratory biomarker analysis||Phase 3|
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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.
I. To determine the feasibility and toxicity of the proposed chemotherapy regimen in combination with radiation therapy.
II. To contribute tumor samples from which biologic and gene expression data can be developed to yield prognostic indicators and provide direction for future treatment strategies.
III. To develop a clinical and biologic database on which future studies can be based.
OUTLINE: This is a multicenter study. Patients are stratified according to age and tumor histology (infants [< 36 months of age] with tumor histology and immunohistochemical [IH] analysis diagnostic of atypical teratoid/rhabdoid CNS tumors [AT/RT] [stratum 1] vs infants with INI1 mutation only-based diagnosis [i.e., histology is not consistent with AT/RT] vs older children [≥ 36 months of age] with tumor histology and IH analysis diagnostic of AT/RT vs older children with INI1 mutation only-based diagnosis).
INDUCTION THERAPY AND STEM CELL HARVEST: Patients receive vincristine IV on days 1, 8, and 15 and high-dose methotrexate IV over 4 hours on day 1. Beginning 24 hours after the start of methotrexate, patients receive leucovorin calcium orally or IV every 6 hours until the serum methotrexate level is < 0.1 micromoles. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6*. Patients also receive filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 7 and continuing until ANC recovers. When ANC is > 1,000/μL post nadir, patients receive G-CSF twice daily for stem cell mobilization. Approximately 2-4 days, later peripheral blood stem cells are harvested once daily, as needed, after each course of induction therapy until a total of 6 x 10^6 CD34+ cells/kg have been collected.
Treatment repeats every 21 days for 2 courses. After completion of induction therapy, patients are re-evaluated. Patients with progressive disease are removed from study. Patients with radiographic evidence of residual tumor are encouraged to undergo second-look surgery prior to proceeding to radiotherapy or consolidation therapy; patients with complete response, partial response, or stable disease proceed to radiation therapy or consolidation therapy depending on age, location of the tumor, and initial diagnosis (whether or not disease is disseminated).**
CONSOLIDATION THERAPY AND STEM CELL RESCUE: Within 2-6 weeks after completion of induction therapy or radiation therapy, patients begin consolidation therapy. Patients receive high-dose carboplatin IV over 4 hours and high-dose thiotepa IV over 2 hours on days 1 and 2 and undergo autologous peripheral blood stem cell (PBSC) rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily beginning 24 hours after stem cell infusion and continuing 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.
RADIATION THERAPY: *Before (but after induction therapy) or after consolidation therapy and stem cell rescue, patients undergo 3-dimensional conformal radiotherapy (3D-CRT) to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
NOTE: *The administration of etoposide, cyclophosphamide, and cisplatin are dependant on the prior clearance of methotrexate to a level of < 0.1 micromoles.
NOTE: **Patients with localized posterior fossa tumors and ≥ 6 months of age at the end of induction therapy OR with localized supratentorial tumors at diagnosis and ≥ 12 months of age at the end of induction therapy proceed to radiotherapy followed by consolidation therapy; patients with disseminated disease at diagnosis, patients with localized posterior fossa tumors at diagnosis and < 6 months of age at the end of induction therapy, or patients with localized supratentorial tumors at diagnosis and < 12 months of age at the end of induction therapy proceed to consolidation therapy followed by radiotherapy. Previously collected tumor tissue is analyzed for a mutation in the INI1 rhabdoid tumor suppressor gene and stained for INI1 antibody.
After completion of study treatment, patients are followed periodically for up to 10 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||70 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System With Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation|
|Study Start Date :||December 2008|
|Actual Primary Completion Date :||April 2015|
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.
Consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses (C) and 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks (R), the order of which depends on patient age, in the absence of disease progression or unacceptable toxicity.
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSC rescue
Radiation: 3-dimensional conformal radiation therapy
Drug: leucovorin calcium
Given IV or orally
Given IV or SC
Drug: vincristine sulfate
Other: laboratory biomarker analysis
- 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.
- Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy [ Time Frame: During protocol therapy up to 1 year after enrollment. ]Number of Participants with Nonhematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00653068
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|Principal Investigator:||Alyssa Reddy, MD||Children's Oncology Group|