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
- Conditions
- Central Nervous System TumorBrain Tumor
- Interventions
- Biological: filgrastimProcedure: autologous bone marrow transplantationProcedure: peripheral blood stem cell transplantation
- Registration Number
- NCT00078988
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin, thiotepa, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Isotretinoin may be effective in preventing recurrence of glioma. It is not yet known which regimen of chemotherapy plus autologous stem cell transplantation with or without isotretinoin is more effective in treating recurrent high-grade glioma.
PURPOSE: This randomized phase III trial is studying high-dose chemotherapy or intermediate-dose chemotherapy followed by autologous stem cell transplantation to see how well it works compared to high-dose chemotherapy or intermediate-dose chemotherapy followed by autologous stem cell transplantation and isotretinoin in treating young patients with recurrent high-grade glioma.
- Detailed Description
OBJECTIVES:
* Compare the event-free survival and overall survival of pediatric patients with recurrent high-grade gliomas treated with a single course of high-dose carboplatin, etoposide, and thiotepa and autologous stem cell transplantation vs multiple courses of intermediate-dose carboplatin and thiotepa and autologous stem cell transplantation with or without isotretinoin.
* Compare the number of hospital days and time to engraftment in patients treated with these regimens.
* Compare the toxic death rate in patients treated with these regimens.
* Compare the tolerability of isotretinoin in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to pathologic diagnosis (glioblastoma multiforme vs anaplastic astrocytoma vs other high-grade glioma).
* Chemotherapy and autologous stem cell reinfusion (ASCR): Patients are randomized to 1 of 2 treatment arms.
* Arm I (high-dose chemotherapy and ASCR): Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 1 and continuing until blood counts recover. Autologous peripheral blood stem cells (PBSC) or bone marrow are reinfused on day 0.
* Arm II (intermediate-dose chemotherapy and ASCR): Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses.
* Maintenance therapy: After recovery from chemotherapy (approximately day 30 post-transplantation), all patients are further randomized to 1 of 2 maintenance arms.
* Arm I: Patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.
* Arm II: Patients do not receive maintenance therapy. In all arms, treatment continues in the absence of disease progression.
Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 80-150 patients (40-75 per treatment arm) will be accrued for this study within 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (high-dose chemotherapy and ASCR) filgrastim Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0. Arm I (high-dose chemotherapy and ASCR) peripheral blood stem cell transplantation Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0. Arm I (high-dose chemotherapy and ASCR) autologous bone marrow transplantation Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0. Arm II (intermediate-dose chemotherapy and ASCR) filgrastim Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses. Arm II (intermediate-dose chemotherapy and ASCR) peripheral blood stem cell transplantation Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses. Arm II (intermediate-dose chemotherapy and ASCR) autologous bone marrow transplantation Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses. Arm III (isotretinoin) isotretinoin Patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses. Arm I (high-dose chemotherapy and ASCR) carboplatin Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0. Arm I (high-dose chemotherapy and ASCR) etoposide Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0. Arm I (high-dose chemotherapy and ASCR) isotretinoin Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0. Arm I (high-dose chemotherapy and ASCR) thiotepa Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0. Arm II (intermediate-dose chemotherapy and ASCR) carboplatin Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses. Arm II (intermediate-dose chemotherapy and ASCR) thiotepa Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses.
- Primary Outcome Measures
Name Time Method Event-free survival om study entry to disease progression, disease relapse, occurrence of a second malignant neoplasm, or death from any cause. assessed up to 4 years The primary endpoint for the evaluation of treatment efficacy will be event-free survival (EFS)
Toxic death attributable to complications of treatment in the absence of tumor progression as assessed by NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 Up to 4 years after completion of study treatment Toxic death will be monitored separately in each of the two chemotherapy groups
- Secondary Outcome Measures
Name Time Method Overall survival (OS) ondary e ndpoints include overall survival (OS), which is defined as the time from study entry to death from any cause assessed up to 4 years Secondary endpoints include overall survival (OS), which is defined as the time from study entry to death from any cause, assessed up to 4 years
Trial Locations
- Locations (59)
Children's Hospital and Health Center - San Diego
🇺🇸San Diego, California, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
Fairview University Medical Center - University Campus
🇺🇸Minneapolis, Minnesota, United States
University of Florida Shands Cancer Center
🇺🇸Gainesville, Florida, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Miami Children's Hospital
🇺🇸Miami, Florida, United States
St. Vincent Indianapolis Hospital
🇺🇸Indianapolis, Indiana, United States
All Children's Hospital
🇺🇸St. Petersburg, Florida, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Siteman Cancer Center at Barnes-Jewish Hospital
🇺🇸St. Louis, Missouri, United States
NYU Cancer Institute at New York University Medical Center
🇺🇸New York, New York, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
CancerCare of Maine at Eastern Maine Medial Center
🇺🇸Bangor, Maine, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Montreal Children's Hospital at McGill University Health Center
🇨🇦Montreal, Quebec, Canada
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Sioux Valley Hospital and University of South Dakota Medical Center
🇺🇸Sioux Falls, South Dakota, United States
Children's Hospital Cancer Center
🇺🇸Denver, Colorado, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital
🇺🇸Tampa, Florida, United States
Emory University Hospital - Atlanta
🇺🇸Atlanta, Georgia, United States
Children's Hospital and Research Center - Oakland
🇺🇸Oakland, California, United States
Kaplan Cancer Center at St. Mary's Medical Center
🇺🇸West Palm Beach, Florida, United States
Columbus Children's Hospital
🇺🇸Columbus, Ohio, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Cancer Research Center of Hawaii
🇺🇸Honolulu, Hawaii, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Floating Hospital for Children at Tufts - New England Medical Center
🇺🇸Boston, Massachusetts, United States
Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Children's Medical Center - Dayton
🇺🇸Dayton, Ohio, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
INOVA Fairfax Hospital
🇺🇸Fairfax, Virginia, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Centre Hospitalier Universitaire de Quebec
🇨🇦Ste-Foy, Quebec, Canada
Oklahoma University Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Herbert Irving Comprehensive Cancer Center at Columbia University
🇺🇸New York, New York, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
Children's Hospital of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Spectrum Health Cancer Care - Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
New York Medical College
🇺🇸Valhalla, New York, United States
University of California Davis Cancer Center
🇺🇸Sacramento, California, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Children's Hospital of the King's Daughters
🇺🇸Norfolk, Virginia, United States
Massey Cancer Center at Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Children's & Women's Hospital of British Columbia
🇨🇦Vancouver, British Columbia, Canada
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia