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
NCT ID: NCT00653068
Last Updated: 2024-04-23
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
70 participants
INTERVENTIONAL
2009-02-10
2024-03-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Combination Chemotherapy, Autologous Stem Cell Transplant, and/or Radiation Therapy in Treating Young Patients With Extraocular Retinoblastoma
NCT00554788
Chemotherapy Combined With Radiation Therapy for Newly Diagnosed CNS AT/RT
NCT00084838
Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Neuroblastoma
NCT00017368
Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
NCT00336024
High-Dose Chemotherapy Plus Autologous Stem Cell Transplantation Compared With Intermediate-Dose Chemotherapy Plus Autologous Stem Cell Transplantation With or Without Isotretinoin in Treating Young Patients With Recurrent High-Grade Gliomas
NCT00078988
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
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:
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 (PO) 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/uL 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 are assigned to 1 of 2 arm.
ARM I ((patients less than 6 months, infratentorial site with M0 involvement or patients less than 12 months, supratentorial site with M0 involvement or patients with disseminated disease of any primary site or age):
CONSOLIDATION THERAPY AND STEM CELL RESCUE: Within 2-6 weeks after completion of induction 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: Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
ARM II (patients greater than or equal to 6 months, infratentorial site with M0 involvement or patients greater than or equal to 12 months, supratentorial site with M0 involvement): Patients undergo 3D-CRT as in Arm I. Within 2-6 weeks after completion of radiation therapy, patients receive consolidation therapy and stem cell rescue as in Arm I
NOTE: \*The administration of etoposide, cyclophosphamide, and cisplatin are dependant on the prior clearance of methotrexate to a level of \< 0.1 micromoles.
After completion of study treatment, patients are followed periodically for up to 10 years.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC rescue
Carboplatin
Given IV
Cisplatin
Given IV
Cyclophosphamide
Given IV
Etoposide
Given IV
Filgrastim
Given IV or SC
Laboratory Biomarker Analysis
Correlative studies
Leucovorin Calcium
Given IV or PO
Methotrexate
Given IV
Thiotepa
Given IV
Vincristine Sulfate
Given IV
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.
3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC rescue
Carboplatin
Given IV
Cisplatin
Given IV
Cyclophosphamide
Given IV
Etoposide
Given IV
Filgrastim
Given IV or SC
Laboratory Biomarker Analysis
Correlative studies
Leucovorin Calcium
Given IV or PO
Methotrexate
Given IV
Thiotepa
Given IV
Vincristine Sulfate
Given IV
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC rescue
Carboplatin
Given IV
Cisplatin
Given IV
Cyclophosphamide
Given IV
Etoposide
Given IV
Filgrastim
Given IV or SC
Laboratory Biomarker Analysis
Correlative studies
Leucovorin Calcium
Given IV or PO
Methotrexate
Given IV
Thiotepa
Given IV
Vincristine Sulfate
Given IV
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
21 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Children's Oncology Group
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Alyssa T Reddy
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Children's Hospital of Alabama
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center
Downey, California, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Valley Children's Hospital
Madera, California, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States
Children's Hospital of Orange County
Orange, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Lee Memorial Health System
Fort Myers, Florida, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 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 Clinic - Pensacola
Pensacola, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, United States
Saint Mary's Hospital
West Palm Beach, Florida, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Norton Children's Hospital
Louisville, Kentucky, United States
Tulane University School of Medicine
New Orleans, Louisiana, United States
Children's Hospital New Orleans
New Orleans, Louisiana, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Morristown Medical Center
Morristown, New Jersey, United States
Saint Joseph's Regional Medical Center
Paterson, New Jersey, United States
Overlook Hospital
Summit, New Jersey, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of Rochester
Rochester, New York, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
New York Medical College
Valhalla, New York, United States
Mission Hospital
Asheville, North Carolina, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Dayton Children's Hospital
Dayton, Ohio, United States
Mercy Children's Hospital
Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Penn State Children's Hospital
Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Rhode Island Hospital
Providence, Rhode Island, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Prisma Health Richland Hospital
Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
Greenville Cancer Treatment Center
Greenville, South Carolina, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States
Driscoll Children's Hospital
Corpus Christi, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 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
Primary Children's Hospital
Salt Lake City, Utah, United States
Seattle Children's Hospital
Seattle, Washington, United States
West Virginia University Charleston Division
Charleston, West Virginia, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Royal Children's Hospital
Parkville, Victoria, Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
Alberta Children's Hospital
Calgary, Alberta, Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada
Kingston Health Sciences Centre
Kingston, Ontario, Canada
Hospital for Sick Children
Toronto, Ontario, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Mazzarella J, Heathcock JC. A Randomized Feasibility Study of Rehabilitation Targeting Upper Extremity Function and Participation Using Hippotherapy and the Equine Environment for Children with Cerebral Palsy and Autism Spectrum Disorder. J Integr Complement Med. 2025 Feb;31(2):196-208. doi: 10.1089/jicm.2024.0292. Epub 2024 Nov 8.
Reddy AT, Krailo MD, Buxton AB, Strother DR, Huang A, Zhou T, Judkins AR, Burger PC, Pollack IF, Williams-Hughes C, Fouladi M, Ho B, Mazewski CM, Lewis VA, Vezina LG, Booth TN, Mahajan A. Reply to S.A. Upadhyaya. J Clin Oncol. 2020 Oct 1;38(28):3353-3354. doi: 10.1200/JCO.20.01573. Epub 2020 Jul 30. No abstract available.
Related Links
Access external resources that provide additional context or updates about the study.
Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2009-00337
Identifier Type: REGISTRY
Identifier Source: secondary_id
CDR0000592812
Identifier Type: -
Identifier Source: secondary_id
09-0058
Identifier Type: -
Identifier Source: secondary_id
COG-ACNS0333
Identifier Type: -
Identifier Source: secondary_id
ACNS0333
Identifier Type: OTHER
Identifier Source: secondary_id
ACNS0333
Identifier Type: OTHER
Identifier Source: secondary_id
ACNS0333
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.