Combination Chemotherapy Followed by Bone Marrow and/or Peripheral Stem Cell Transplantation in Treating Patients With Recurrent Medulloblastoma or CNS Germ Cell Tumors

Dose-Intensive Melphalan and Cyclophosphamide With Autologous Bone Marrow Rescue for Recurrent Medulloblastoma and Germ Cell Tumors

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.

Study Overview

• Status: Completed
• Conditions: Brain Tumor; Central Nervous System Tumor
• Intervention / Treatment: Drug: cyclophosphamide; Procedure: peripheral blood stem cell transplantation; Procedure: autologous bone marrow transplantation; Drug: melphalan; Procedure: bone marrow ablation with stem cell support; Biological: Sargramostim

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ablative chemo followed by autologous bone marrow (ABM) rescue; 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.

Drug: cyclophosphamide; Given IV; Other Names: Cytoxan; NSC #026271; IND #7089; Procedure: peripheral blood stem cell transplantation; Procedure: autologous bone marrow transplantation; Drug: melphalan; Given IV; Other Names: Alkeran; L-PAM; L-sarcolysin; NSC #8806; ylalanine mustard; Procedure: bone marrow ablation with stem cell support; Biological: Sargramostim; Given IV; Other Names: Leukine; Prokine; GM-CSF; Granulocyte macrophage-colony stimulating factor; M-CSF; NSC #6137

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	1-2 years

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Donald H. Mahoney, MD, Texas Children's Cancer Center

Publications and helpful links

General Publications

• Kadota RP, Mahoney DH, Doyle J, Duerst R, Friedman H, Holmes E, Kun L, Zhou T, Pollack IF. Dose intensive melphalan and cyclophosphamide with autologous hematopoietic stem cells for recurrent medulloblastoma or germinoma. Pediatr Blood Cancer. 2008 Nov;51(5):675-8. doi: 10.1002/pbc.21655.

Study record dates

Study Major Dates

• Study Start: September 1, 1994
• Primary Completion (Actual): September 1, 2003
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 24, 2014
• Last Update Submitted That Met QC Criteria: July 23, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: recurrent childhood brain tumor; recurrent childhood medulloblastoma; childhood central nervous system germ cell tumor
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neoplasms; Neoplasms, Germ Cell and Embryonal; Brain Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Medulloblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Melphalan; Sargramostim; Molgramostim
• Other Study ID Numbers: 9430; COG-P9430 (Other Identifier: Children's Oncology Group); POG-9430 (Other Identifier: Pediatric Oncology Group); CDR0000063784 (Other Identifier: NCI)