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

Brain Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002594
• Other study ID #: 9430
• Secondary ID: COG-P9430POG-943
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: July 23, 2014
• Start date: September 1994
• Est. completion date: March 2007

Study information

• Verified date: July 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: March 2007
• Est. primary completion date: September 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 25 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumor
• Central Nervous System Neoplasms
• Central Nervous System Tumor
• Medulloblastoma
• Neoplasms
• Nervous System Neoplasms

Intervention

Biological:
• Sargramostim
Given IV

Drug:
• cyclophosphamide
Given IV
• melphalan
Given IV

Procedure:
• autologous bone marrow transplantation

• bone marrow ablation with stem cell support

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Brisbane	Queensland
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Children's Hospital at Westmead	Westmead	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Chedoke-McMaster Hospitals	Hamilton	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	McGill University Health Center - Montreal Children's Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre de Recherche du Centre Hospitalier de l'Universite Laval	Sainte Foy	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Puerto Rico	San Jorge Childrens Hospital	Santurce
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Swiss Pediatric Oncology Group Geneva	Geneva
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	Mission St. Joseph's Health System	Asheville	North Carolina
United States	Children's Healthcare of Atlanta - Scottish Rite	Atlanta	Georgia
United States	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Floating Hospital for Children	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University - Charleston	Charleston	West Virginia
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Healthcare	Charlotte	North Carolina
United States	Cancer Center at the University of Virginia	Charlottesville	Virginia
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	University of Missouri-Columbia Hospital and Clinics	Columbia	Missouri
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	St. John Hospital and Medical Center	Detroit	Michigan
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Hurley Medical Center	Flint	Michigan
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Shands Hospital and Clinics, University of Florida	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Children's Hospital of Greenville Hospital System	Greenville	South Carolina
United States	East Carolina University School of Medicine	Greenville	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Joe DiMaggio Children's Hospital at Memorial	Hollywood	Florida
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Texas Children's Cancer Center	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	East Tennessee State University Cancer Center at JCMC	Johnson City	Tennessee
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Baptist Hospital of Miami	Miami	Florida
United States	Miami Children's Hospital	Miami	Florida
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	University of South Alabama Medical Center	Mobile	Alabama
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	Yale Comprehensive Cancer Center	New Haven	Connecticut
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	Children's Hospital of New Orleans	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Beth Israel Hospital North	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Advocate Hope Children's Hospital	Oak Lawn	Illinois
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Nemours Children's Clinic-Orlando	Orlando	Florida
United States	Sacred Heart Children's Hospital	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Naval Medical Center, Portsmouth	Portsmouth	Virginia
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Massey Cancer Center	Richmond	Virginia
United States	Carilion Medical Center for Children	Roanoke	Virginia
United States	James P. Wilmot Cancer Center	Rochester	New York
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University Medical Center	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Children's Hospital San Diego	San Diego	California
United States	Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego	San Diego	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Maine Children's Cancer Program	Scarborough	Maine
United States	All Children's Hospital	St. Petersburg	Florida
United States	Stanford University Medical Center	Stanford	California
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Tampa Children's Hospital	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Arizona Cancer Center	Tucson	Arizona
United States	Warren Clinic	Tulsa	Oklahoma
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	St. Mary's Hospital	West Palm Beach	Florida
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Netherlands,  Puerto Rico,  Switzerland, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		1-2 years	No