RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so that they stop growing or die. bone marrow transplantation and peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by bone marrow transplantation and/or peripheral stem cell transplantation in treating patients who have recurrent medulloblastoma or CNS germ cell tumors.

Condition	Treatment or Intervention	Phase
recurrent childhood brain tumor childhood central nervous system germ cell tumor recurrent childhood medulloblastoma	Drug: cyclophosphamide  Drug: melphalan  Drug: sargramostim  Procedure: autologous bone marrow transplantation  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: high-dose chemotherapy  Procedure: peripheral blood stem cell transplantation	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the response and progression-free survival in patients with recurrent medulloblastoma or CNS germ cell tumors treated with intensive melphalan and cyclophosphamide followed by autologous bone marrow and/or peripheral blood stem cell rescue.
• Determine the acute and delayed toxic effects of this regimen in these patients.

OUTLINE: Autologous bone marrow and/or peripheral blood stem cells (PBSC) are harvested. Patients then receive intensive cyclophosphamide IV over 1 hour on days -8 to -5 and melphalan IV over 15 minutes on days -4 to -2. Bone marrow is reinfused on day 0. PBSC are reinfused on day 0 if used alone or on day 1 if used after autologous bone marrow transplantation (ABMT). Sargramostim (GM-CSF) is administered IV over 2 hours daily beginning 4 hours after ABMT and continuing until blood counts recover.

Patients are followed every 6 months through year 4 and then annually thereafter.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 2.5 years.

Ages Eligible for Study:  2 Years   -   25 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of recurrent medulloblastoma or CNS germ cell tumor
• Histologic review of the primary intracranial or spinal cord tumor required
• Biopsy and reduction of tumor bulk prior to study encouraged but not required
• No more than 1 prior primary therapy (radiotherapy or chemoradiotherapy) and/or 1 prior salvage therapy
• Patients with progression on salvage therapy ineligible
• Minimal residual disease (tumor bulk no more than 1.5 cm) or in second clinical complete remission (CR)
• Bone marrow infiltration with or without mass lesions or isolated abnormal CSF cytology as the only manifestation of recurrent disease allowed if a clinical CR is first achieved with conventional therapy

PATIENT CHARACTERISTICS: Age:

• 2 to 25

Performance status:

• Karnofsky 80-100%

Life expectancy:

• More than 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• SGPT less than 80 IU

Renal:

• Creatinine less than 1.2 mg/dL

Cardiovascular:

• LVEF normal

Other:

• No infection
• Able to tolerate vigorous hydration
• Not pregnant
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• Prior cyclophosphamide or ifosfamide allowed

Endocrine therapy:

• No concurrent dexamethasone as an antiemetic
• Other concurrent corticosteroids allowed

Radiotherapy:

• See Disease Characteristics
• Pretransplantation radiotherapy boost allowed

Surgery:

• See Disease Characteristics
• Pretransplantation surgery allowed

Other:

• At least 4 weeks since prior therapy except corticosteroids

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35233,  United States
      University of South Alabama Medical Center, Mobile,  Alabama,  36604,  United States
Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      Children's Hospital San Diego, San Diego,  California,  92123-4282,  United States
      Kaiser Permanente Medical Center - Santa Clara, Santa Clara,  California,  95051-5386,  United States
      Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego, San Diego,  California,  92120,  United States
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States
      Stanford University Medical Center, Stanford,  California,  94305-5208,  United States
      Sutter Cancer Center, Sacramento,  California,  95816,  United States
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States
Connecticut
      Yale Comprehensive Cancer Center, New Haven,  Connecticut,  06520-8028,  United States
District of Columbia
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States
Florida
      All Children's Hospital, St. Petersburg,  Florida,  33701,  United States
      Baptist Hospital of Miami, Miami,  Florida,  33176-2197,  United States
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States
      Children's Hospital of Southwest Florida, Fort Myers,  Florida,  33908,  United States
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States
      Joe DiMaggio Children's Hospital at Memorial, Hollywood,  Florida,  33021,  United States
      Miami Children's Hospital, Miami,  Florida,  33155-4069,  United States
      Nemours Children's Clinic, Jacksonville,  Florida,  32207,  United States
      Nemours Children's Clinic-Orlando, Orlando,  Florida,  32806,  United States
      Sacred Heart Children's Hospital, Pensacola,  Florida,  32504,  United States
      Shands Hospital and Clinics, University of Florida, Gainesville,  Florida,  32610-100277,  United States
      St. Mary's Hospital, West Palm Beach,  Florida,  33407,  United States
      Sylvester Cancer Center, University of Miami, Miami,  Florida,  33136,  United States
      Tampa Children's Hospital, Tampa,  Florida,  33677-4227,  United States
Georgia
      Children's Healthcare of Atlanta - Scottish Rite, Atlanta,  Georgia,  30342,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813,  United States
      Tripler Army Medical Center, Honolulu,  Hawaii,  96859-5000,  United States
Illinois
      Advocate Hope Children's Hospital, Oak Lawn,  Illinois,  60453,  United States
      Children's Memorial Hospital - Chicago, Chicago,  Illinois,  60614,  United States
      Rush-Presbyterian-St. Luke's Medical Center, Chicago,  Illinois,  60612,  United States
      Saint Jude Midwest Affiliate, Peoria,  Illinois,  61637,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
      Via Christi Regional Medical Center, Wichita,  Kansas,  67214,  United States
      Wesley Medical Center, Wichita,  Kansas,  67214,  United States
Louisiana
      Children's Hospital of New Orleans, New Orleans,  Louisiana,  70118,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Ochsner Clinic Foundation, New Orleans,  Louisiana,  70121,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maine
      Eastern Maine Medical Center, Bangor,  Maine,  04401,  United States
      Maine Children's Cancer Program, Scarborough,  Maine,  04074-9308,  United States
Maryland
      Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201-1595,  United States
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      Floating Hospital for Children, Boston,  Massachusetts,  02111,  United States
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States
      University of Massachusetts Memorial Medical Center - University Campus, Worcester,  Massachusetts,  01655,  United States
Michigan
      Children's Hospital of Michigan, Detroit,  Michigan,  48201,  United States
      Hurley Medical Center, Flint,  Michigan,  48503,  United States
      St. John Hospital and Medical Center, Detroit,  Michigan,  48236,  United States
Mississippi
      Keesler Medical Center - Keesler AFB, Keesler AFB,  Mississippi,  39534-2511,  United States
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
Missouri
      Cardinal Glennon Children's Hospital, Saint Louis,  Missouri,  63104,  United States
      University of Missouri-Columbia Hospital and Clinics, Columbia,  Missouri,  65212,  United States
      Washington University Medical Center, Saint Louis,  Missouri,  63105,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States
New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
New Mexico
      University of New Mexico Cancer Research and Treatment Center, Albuquerque,  New Mexico,  87131,  United States
New York
      Beth Israel Hospital North, New York,  New York,  10128,  United States
      James P. Wilmot Cancer Center, Rochester,  New York,  14642,  United States
      Mount Sinai School of Medicine, New York,  New York,  10029,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      Schneider Children's Hospital, New Hyde Park,  New York,  11042,  United States
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
      State University of New York Health Sciences Center - Stony Brook, Stony Brook,  New York,  11790-7775,  United States
North Carolina
      Carolinas Medical Center, Charlotte,  North Carolina,  28232-2861,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1081,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      East Carolina University School of Medicine, Greenville,  North Carolina,  27858-4354,  United States
      Mission St. Joseph's Health System, Asheville,  North Carolina,  28801,  United States
      Presbyterian Healthcare, Charlotte,  North Carolina,  28233,  United States
Oklahoma
      University of Oklahoma Health Sciences Center, Oklahoma City,  Oklahoma,  73104,  United States
      Warren Clinic, Tulsa,  Oklahoma,  74136,  United States
Oregon
      Legacy Emanuel Hospital and Health Center, Portland,  Oregon,  97227,  United States
Pennsylvania
      St. Christopher's Hospital for Children, Philadelphia,  Pennsylvania,  19134-1095,  United States
Rhode Island
      Rhode Island Hospital, Providence,  Rhode Island,  02818,  United States
South Carolina
      Children's Hospital of Greenville Hospital System, Greenville,  South Carolina,  29605,  United States
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
Tennessee
      East Tennessee State University Cancer Center at JCMC, Johnson City,  Tennessee,  37604,  United States
      St. Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States
Texas
      Cook Children's Medical Center - Fort Worth, Fort Worth,  Texas,  76104,  United States
      Driscoll Children's Hospital, Corpus Christi,  Texas,  78466,  United States
      Medical City Dallas Hospital, Dallas,  Texas,  75230,  United States
      San Antonio Military Pediatric Cancer and Blood Disorders Center, Lackland Air Force Base,  Texas,  78236,  United States
      Scott and White Memorial Hospital, Temple,  Texas,  76508,  United States
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States
      Texas Children's Cancer Center, Houston,  Texas,  77030-2399,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78207,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-0361,  United States
Vermont
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
Virginia
      Cancer Center at the University of Virginia, Charlottesville,  Virginia,  22908,  United States
      Carilion Medical Center for Children, Roanoke,  Virginia,  24029,  United States
      Inova Fairfax Hospital, Falls Church,  Virginia,  22042-3300,  United States
      Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Naval Medical Center, Portsmouth, Portsmouth,  Virginia,  23708-5100,  United States
Washington
      Madigan Army Medical Center, Tacoma,  Washington,  98431-5000,  United States
West Virginia
      West Virginia University - Charleston, Charleston,  West Virginia,  25302,  United States
      West Virginia University Hospitals, Morgantown,  West Virginia,  26506-9300,  United States
Wisconsin
      Midwest Children's Cancer Center, Milwaukee,  Wisconsin,  53226,  United States
      St. Vincent Hospital, Green Bay,  Wisconsin,  54307-9070,  United States
Australia, New South Wales
      Children's Hospital at Westmead, Westmead,  New South Wales,  2145,  Australia
Australia, Queensland
      Royal Children's Hospital, Brisbane,  Queensland,  4029,  Australia
Australia, Victoria
      Royal Children's Hospital, Parkville,  Victoria,  3052,  Australia
Canada, Alberta
      Alberta Children's Hospital, Calgary,  Alberta,  T2T 5C7,  Canada
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
Canada, Ontario
      Chedoke-McMaster Hospitals, Hamilton,  Ontario,  L8N 3Z5,  Canada
      Children's Hospital of Eastern Ontario, Ottawa,  Ontario,  K1H 8L1,  Canada
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada
Canada, Quebec
      Centre de Recherche du Centre Hospitalier de l'Universite Laval, Sainte-Foy,  Quebec,  GIV 4G2,  Canada
      Hopital Sainte Justine, Montreal,  Quebec,  H3T 1C5,  Canada
      McGill University Health Center - Montreal Children's Hospital, Montreal,  Quebec,  H3G 1A4,  Canada
Netherlands
      Academisch Ziekenhuis Groningen, Groningen,  9700 RB,  Netherlands
Puerto Rico
      San Jorge Childrens Hospital, Santurce,  00912,  Puerto Rico
Switzerland
      Swiss Pediatric Oncology Group Bern, Bern,  CH 3010,  Switzerland
      Swiss Pediatric Oncology Group Geneva, Geneva,  CH 1211,  Switzerland

Study chairs or principal investigators

Donald H. Mahoney, MD,  Study Chair,  Texas Children's Cancer Center   

Study ID Numbers:  CDR0000063784; COG-P9430; POG-9430
Record last reviewed:  November 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002594
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08