Antibiotic Therapy With or Without G-CSF in Treating Children With Neutropenia and Fever Caused by Chemotherapy

Neutropenia Clinical Trial

Official title:

Randomized Comparison Between Antibiotics Alone and Antibiotics Plus Granulocyte-Colony Stimulating Factor in Pediatric Patients With Chemotherapy Induced Febrile Neutropenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003739
• Other study ID #: AS973
• Secondary ID: COG-AS973COG-S97
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: February 12, 2014
• Start date: March 1999
• Est. completion date: September 2006

Study information

• Verified date: February 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: Antibiotics may decrease the side effects of neutropenia and fever caused by chemotherapy. Colony-stimulating factors such as G-CSF may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. It is not yet known whether antibiotic therapy plus G-CSF is more effective than antibiotic therapy alone for treating side effects caused by chemotherapy.

PURPOSE: Randomized phase III trial to compare the effectiveness of antibiotic therapy with or without G-CSF in treating children who have neutropenia and fever that are caused by chemotherapy.

Description:

OBJECTIVES:

• Determine whether filgrastim (G-CSF) used in addition to standard antibiotic therapy accelerates time to resolution of febrile neutropenia in children receiving chemotherapy.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive standard antibiotic therapy.

• Arm II: Patients receive treatment as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously or IV once a day until at least 2 consecutive afebrile days have passed and absolute neutrophil count is at least 500/mm3.

Patients are followed for 3 days.

PROJECTED ACCRUAL: A total of 200 patients (100 per treatment arm) will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: September 2006
• Est. primary completion date: December 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically diagnosed cancer with fever and chemotherapy-induced neutropenia (absolute neutrophil count no greater than 500/mm3)

• Acute onset of fever of at least 38.8 degrees Celsius that is not related to the administration of blood products or pyrogenic substances

• No acute myelogenous leukemia

• No myelodysplastic syndrome

• No solid tumor with bone marrow involvement

PATIENT CHARACTERISTICS:

Age:

• 21 and under

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Creatinine less than 1.5 times upper limit of normal

Renal:

• Not specified

Other:

• No patients in septic shock

• No prolonged fever of unknown origin

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

• See Chemotherapy

Chemotherapy:

• No prior or concurrent myeloablative chemoradiotherapy with bone marrow or peripheral stem cell rescue

Endocrine therapy:

• Not specified

Radiotherapy:

• See Chemotherapy

• No prior radiotherapy to marrow reserves (i.e., craniospinal and/or pelvic irradiation)

Surgery:

• Not specified

Other:

• At least 7 days since prior IV antibiotics

Study Design

Allocation: Randomized, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Chemotherapy-Induced Febrile Neutropenia
• Fever
• Fever, Sweats, and Hot Flashes
• Hot Flashes
• Neutropenia
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Biological:
• filgrastim

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Brisbane	Queensland
Australia	Women's and Children's Hospital	North Adelaide	South Australia
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Sydney Children's Hospital	Randwick	New South Wales
Australia	Children's Hospital at Westmead	Westmead	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Children's Hospital	Hamilton	Ontario
Canada	Children's Hospital of Western Ontario	London	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	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Centre Hospitalier de L'Universite Laval	Sainte Foy	Quebec
Canada	Laval University Medical Center	Sainte-Foy	Quebec
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Janeway Children's Health and Rehabilitation Centre	St. John's	Newfoundland and Labrador
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Netherlands	Academisch Ziekenhuis Groningen	Groningen
New Zealand	Starship Children's Hospital	Auckland
Puerto Rico	University of Puerto Rico School of Medicine Medical Sciences Campus	San Juan
Puerto Rico	San Jorge Childrens Hospital	Santurce
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Swiss Pediatric Oncology Group Geneva	Geneva
Switzerland	Swiss Pediatric Oncology Group Lausanne	Lausanne
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Cancer Center of Albany Medical Center	Albany	New York
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	Texas Tech University Health Sciences Center School of Medicine	Amarillo	Texas
United States	Mott Children's Hospital	Ann Arbor	Michigan
United States	Mission Saint Joseph's Health System	Asheville	North Carolina
United States	Children's Healthcare of Atlanta - Scottish Rite	Atlanta	Georgia
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Medical College of Georgia Comprehensive Cancer Center	Augusta	Georgia
United States	Children's Hospital of Austin	Austin	Texas
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	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Mountain States Tumor Institute	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Floating Hospital for Children	Boston	Massachusetts
United States	Albert Einstein Clinical Cancer Center	Bronx	New York
United States	Brookdale University Hospital and Medical Center	Brooklyn	New York
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Maimonides Medical Center	Brooklyn	New York
United States	State University of New York Health Science Center at Brooklyn College of Medicine	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
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 Chicago Cancer Research Center	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	Palmetto Health South Carolina Cancer Center	Columbia	South Carolina
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Children's Medical Center - Dayton	Dayton	Ohio
United States	Childhood Hematology/Oncology Associates	Denver	Colorado
United States	Children's Hospital of Denver	Denver	Colorado
United States	Presbyterian-St Luke's Medical Center	Denver	Colorado
United States	John Stoddard Cancer Center	Des Moines	Iowa
United States	Raymond Blank Memorial Hospital for Children	Des Moines	Iowa
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	St. John Hospital and Medical Center	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	St. Mary's/Duluth Clinic Cancer Center	Duluth	Minnesota
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Michigan State University	East Lansing	Michigan
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Dakota Cancer Institute	Fargo	North Dakota
United States	University of Connecticut Health Center	Farmington	Connecticut
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	Spectrum Health and DeVos Children's Hospital	Grand Rapids	Michigan
United States	Bellin Memorial Hospital	Green Bay	Wisconsin
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
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	Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Joe DiMaggio Children's Hospital at Memorial	Hollywood	Florida
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	MBCCOP - Hawaii	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Cabell-Huntington Hospital, Inc	Huntington	West Virginia
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	St. Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa
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	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
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	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Jonathan Jaques Children's Cancer Center	Long Beach	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Medical Center of Central Georgia	Macon	Georgia
United States	Children's Hospital Central California	Madera	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Saint 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	University of Miami-Jackson Memorial Hospital	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics - Minneapolis	Minneapolis	Minnesota
United States	University of South Alabama Medical Center	Mobile	Alabama
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
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	Ochsner Clinic	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Columbia Presbyterian Hospital	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	New York Presbyterian Hospital - Cornell Campus	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Hope Children's Hospital	Oak Lawn	Illinois
United States	Children's Hospital of Oakland	Oakland	California
United States	Children's Hospital of Oklahoma	Oklahoma City	Oklahoma
United States	Children's Hospital of Omaha	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	Children's Hospital of Orange County	Orange	California
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Nemours Children's Clinic-Orlando	Orlando	Florida
United States	Lucile Packard Children's Hospital at Stanford	Palo Alto	California
United States	Lutheran General Hospital	Park Ridge	Illinois
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Sacred Heart Children's Hospital	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Doernbecher Children's Hospital	Portland	Oregon
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	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CCOP - Beaumont	Royal Oak	Michigan
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Medical Center	Sacramento	California
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Children's Hospitals and Clinics of Minnesota	Saint Paul	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Methodist Health Care System	San Antonio	Texas
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 - San Francisco Geary Campus	San Francisco	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Santa Barbara Cottage Hospital	Santa Barbara	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Memorial Health University Medical Center, Inc.	Savannah	Georgia
United States	Maine Children's Cancer Program	Scarborough	Maine
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Cooperative	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sioux Valley Hospital	Sioux Falls	South Dakota
United States	Deaconess Medical Center	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	All Children's Hospital	St. Petersburg	Florida
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	Atlantic Health System	Summit	New Jersey
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Mary Bridge Children's Health Center	Tacoma	Washington
United States	Tampa Children's Hospital	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Children's Hospital	Toledo	Ohio
United States	David Grant Medical Center	Travis Air Force Base	California
United States	Arizona Cancer Center	Tucson	Arizona
United States	CCOP - Oklahoma	Tulsa	Oklahoma
United States	Natalie Warren Bryant Cancer Center	Tulsa	Oklahoma
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	Lombardi Cancer Center	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	St. Mary's Hospital	West Palm Beach	Florida
United States	Wesley Medical Center	Wichita	Kansas
United States	Alfred I. Dupont Institute	Wilmington	Delaware
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
United States	Forum Health-Tod Childrens Hospital	Youngstown	Ohio

Sponsors (2)

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

Countries where clinical trial is conducted

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

References & Publications (2)

Ozkaynak MF, Krailo M, Chen N, et al.: Randomized comparison of antibiotics alone and with granulocyte colony-stimulating factor (G-CSF) in children with chemotherapy-induced febrile neutropenia: a report from the Children's Oncology Group. [Abstract] 200

Ozkaynak MF, Krailo M, Chen Z, Feusner J. Randomized comparison of antibiotics with and without granulocyte colony-stimulating factor in children with chemotherapy-induced febrile neutropenia: a report from the Children's Oncology Group. Pediatr Blood Can — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Resolution of Febrile Neutropenia	Time to Resolution of Febrile Neutropenia (Days of antibiotic treatment until the resolution of febrile neutropenia): The time to resolution of febrile neutropenia is defined as the number of days elapsed before the first day with both a temperature of less than 38.0oC and an ANC of equal to or greater than 500/µL.		No
Secondary	Incidence of Change of the Initial Empiric Antibiotic Treatment	The Incidence of Change of the Initial Empiric Antibiotic Treatment: Any change in the initial empiric broad spectrum antibiotic treatment made during the febrile neutropenia period. There may be changes made in the antibiotic(s) after the resolution of febrile neutropenia.		No