Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Infants With Malignant Brain or Spinal Cord Tumors
- Conditions
- Brain TumorsCentral Nervous System TumorsNeuroblastomaSarcoma
- Interventions
- Biological: filgrastimProcedure: conventional surgeryProcedure: peripheral blood stem cell transplantation
- Registration Number
- NCT00003141
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctors to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating infants with malignant brain or spinal cord tumors.
- Detailed Description
OBJECTIVES:
* Determine the maximum tolerated dose of thiotepa in infants with malignant brain or spinal cord tumors receiving intensive chemotherapy.
* Determine the feasibility and toxicity of intensive chemotherapy with peripheral blood stem cell (PBSC) rescue in these patients.
* Assess the feasibility of harvesting PBSCs in these patients.
* Determine the complete response rate and overall event-free survival rate in patients treated with this regimen.
OUTLINE: This is a pilot, multicenter study.
Patients undergo surgery for diagnosis and maximal tumor resection.
Within 6 weeks of surgery or when stable, patients begin induction chemotherapy comprising cisplatin IV over 6 hours on day 0; vincristine IV on days 0, 7, and 14; cyclophosphamide IV over 1 hour on days 1-2; and etoposide IV over 1 hour on days 0-2. Twenty four hours after the last cyclophosphamide dose, patients receive filgrastim (G-CSF) subcutaneously (SC) and undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Within 6 weeks after induction chemotherapy, patients receive consolidation chemotherapy comprising carboplatin IV over 2 hours on days 0-1 followed immediately by escalating doses of thiotepa IV over 2 hours. Patients then undergo peripheral blood stem cell transplantation 48 hours after the last thiotepa dose. Patients receive G-CSF SC daily on days 3 to 21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Patients experiencing dose-limiting toxicity due to thiotepa are removed from the study.
Patients are followed at 4 weeks, every 3 months for 1 year, every 6 months for 3 years, and then annually for 3 years or until relapse.
PROJECTED ACCRUAL: A total of 83 patients will be accrued for this study within 1 year.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 94
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (combination chemotherapy, PBSC transplant) peripheral blood stem cell transplantation Pts undergo conventional surgery for diagnosis \& max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) \& undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse. Treatment (combination chemotherapy, PBSC transplant) filgrastim Pts undergo conventional surgery for diagnosis \& max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) \& undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse. Treatment (combination chemotherapy, PBSC transplant) carboplatin Pts undergo conventional surgery for diagnosis \& max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) \& undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse. Treatment (combination chemotherapy, PBSC transplant) cisplatin Pts undergo conventional surgery for diagnosis \& max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) \& undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse. Treatment (combination chemotherapy, PBSC transplant) thiotepa Pts undergo conventional surgery for diagnosis \& max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) \& undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse. Treatment (combination chemotherapy, PBSC transplant) conventional surgery Pts undergo conventional surgery for diagnosis \& max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) \& undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse. Treatment (combination chemotherapy, PBSC transplant) vincristine sulfate Pts undergo conventional surgery for diagnosis \& max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) \& undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse. Treatment (combination chemotherapy, PBSC transplant) cyclophosphamide Pts undergo conventional surgery for diagnosis \& max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) \& undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse. Treatment (combination chemotherapy, PBSC transplant) etoposide Pts undergo conventional surgery for diagnosis \& max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) \& undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse.
- Primary Outcome Measures
Name Time Method Feasibility Up to 4 weeks after completion of study treatment Demonstrate the feasibility of administering this regimen, to select an acceptable Thiotepa dose for Consolidation therapy, and to document significant toxicities and estimate their overall rates
Maximal tolerated dose of thiotepa for consolidation therapy 9 weeks The dose level will be assigned within 3 working days prior to beginning Consolidation.
Overall rates of significant toxicities including grade IV ototoxicity, electrolytic wasting (grade IV), and hemorrhagic cystitis (grade IV) Up to 6 years Estimates will be obtained using life-table methods with an event defined as the first occurrence of toxicity. Graded using the CCG Toxicity and Complications Criteria.
- Secondary Outcome Measures
Name Time Method Event Free Survival From the time of study entry to the first occurrence of death by any cause, progression or recurrence of disease or occurrence of a second malignant neoplasm, assessed up
Trial Locations
- Locations (71)
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Lucille P. Markey Cancer Center at University of Kentucky
🇺🇸Lexington, Kentucky, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
🇺🇸Atlanta, Georgia, United States
Medical University of Ohio Cancer Center
🇺🇸Toledo, Ohio, United States
Kaiser Permanente Medical Center - Oakland
🇺🇸Sacramento, California, United States
Overlook Hospital
🇺🇸Morristown, New Jersey, United States
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
C.S. Mott Children's Hospital at University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Masonic Cancer Center at University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Butterworth Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
NYU Cancer Institute at New York University Medical Center
🇺🇸New York, New York, United States
MBCCOP - Medical College of Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
Children's Hospitals and Clinics of Minnesota - St. Paul
🇺🇸St. Paul, Minnesota, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸New York, New York, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Texas Tech University Health Sciences Center School of Medicine - Amarillo
🇺🇸Amarillo, Texas, United States
Beth Israel Medical Center - Petrie Division
🇺🇸New York, New York, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Presbyterian - St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Knight Cancer Institute at Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Children's Hospital and Research Center Oakland
🇺🇸Oakland, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Jonsson Comprehensive Cancer Center at UCLA
🇺🇸Los Angeles, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Children's Hospital Center for Cancer and Blood Disorders
🇺🇸Aurora, Colorado, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
CCOP - Kalamazoo
🇺🇸Kalamazoo, Michigan, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
St. Joseph's Hospital and Medical Center
🇺🇸Paterson, New Jersey, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸Sioux Falls, South Dakota, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Group Health Central Hospital
🇺🇸Seattle, Washington, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Carol G. Simon Cancer Center at Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
CCOP - MeritCare Hospital
🇺🇸Fargo, North Dakota, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Dayton Children's - Dayton
🇺🇸Dayton, Ohio, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Deaconess Medical Center
🇺🇸Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center - Tacoma
🇺🇸Tacoma, Washington, United States
Allan Blair Cancer Centre at Pasqua Hospital
🇨🇦Regina, Saskatchewan, Canada
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Children's & Women's Hospital of British Columbia
🇨🇦Vancouver, British Columbia, Canada