Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Giving antibiotics may be effective in preventing or controlling early infection in patients receiving chemotherapy or undergoing stem cell transplant for acute leukemia. It is not yet known whether levofloxacin is effective in preventing infection.

PURPOSE: This randomized phase III trial studies how well levofloxacin works in preventing infection in young patients receiving chemotherapy for acute leukemia or undergoing stem cell transplant.

Further Study Information

OBJECTIVES:

Primary

• To determine whether levofloxacin given prophylactically during periods of neutropenia to patients being treated with chemotherapy for acute leukemia (AL) or undergoing hematopoietic stem cell transplantation (HSCT) will decrease the incidence of bacteremia.

Secondary

• To determine the effect of prophylactic levofloxacin on resistance patterns of bacterial isolates from all sterile site cultures, and the evolution of antimicrobial resistance from peri-rectal swab isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Streptococcus mitis.

• To determine the effect of levofloxacin prophylaxis on total number of days of antibiotic administration (prophylactic, empiric, and treatment) in children undergoing therapy for AL or HSCT.

• To determine whether levofloxacin prophylaxis reduces the incidence of fever with neutropenia, severe infection, and death from bacterial infection.

• To assess the safety of levofloxacin prophylaxis, with specific attention to musculoskeletal disorders including tendinopathy and tendon rupture.

• To assess the impact of prophylactic levofloxacin on the incidence of Clostridium difficile-associated diarrhea (CDAD), and the incidence of microbiologically documented invasive fungal infections (IFI).

OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (de novo acute myeloid leukemia [AML] vs secondary AML vs relapsed AML vs relapsed acute lymphoblastic leukemia [ALL]), and therapy (undergoing autologous HSCT vs undergoing allogeneic HSCT). Patients are randomized to 1 of 2 treatment groups.

• Arm I: Patients receive levofloxacin orally (PO) or IV over 60-90 minutes once or twice daily beginning on day 1 during 2 consecutive courses of chemotherapy or beginning on day -2 during hematopoietic stem cell transplantation (HSCT) and continuing until blood counts recover.

• Arm II: Patients receive established standard of care and receive chemotherapy or HSCT as patients in arm 1.

Musculoskeletal assessment is conducted at baseline and at 2 and 12 months.

Patients may undergo perirectal or stool swab collection for ancillary studies.

After completion of study therapy, patients are followed up for 1 year.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Patients must fit 1 of the following categories:

• Chemotherapy patients

• Scheduled to receive at least 2 consecutive courses (not required to be the first 2 courses) of intensive chemotherapy for de novo, relapsed, or secondary acute myeloid leukemia (AML), or relapsed acute lymphoblastic leukemia (ALL)

• For the purposes of this study, "intensive chemotherapy" is defined as regimens that are predicted by the local Investigator to cause neutropenia for > 7 days including, but not limited to:

• Treatment with "4-drug induction" (anthracycline, vincristine, asparaginase, and steroid)

• High-dose cytarabine, anthracycline/cytarabine, or ifosfamide/etoposide

• Clofarabine-containing regimens

• Stem cell transplantation patients*

• Scheduled to receive at least 1 myeloablative autologous or allogeneic hematopoietic stem cell transplantation (HSCT)

• For the purposes of this study, myeloablative autologous and allogeneic HSCT are those in which the conditioning regimen is predicted by the local Investigator to cause neutropenia for > 7 days NOTE: *Patients with AML or ALL who were enrolled on this study during intensive chemotherapy are not eligible to be enrolled during HSCT.

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Creatinine clearance or radioisotope GFR > 70 mL/min OR serum creatinine based on age and/or gender as follows:

• 0.5 mg/dL (6 months to < 1 year of age)

• 0.6 mg/dL (1 to < 2 years of age)

• 0.8 mg/dL (2 to < 6 years of age)

• 1.0 mg/dL (6 to < 10 years of age)

• 1.2 mg/dL (10 to < 13 years of age)

• 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

• 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

• No patients with an allergy to quinolones

• No patients with chronic active arthritis

• No patients with a known pathologic prolongation of the QTc

• No females who are pregnant or breast feeding

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No patients scheduled to receive non-intensive or palliative chemotherapy

• No patients undergoing non-myeloablative hematopoietic stem cell transplantation (HSCT)

• No patients being treated with antibacterial agents, other than cotrimoxazole for Pneumocystitis jiroveci (PCP) prophylaxis

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

Sarah Alexander

Study Chair

U.S.A.
Arkansas
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		David L Becton	Ph: 501-364-7373
California
	Arcadia
	Children's Oncology Group
		Sarah W Alexander	Ph: 416-813-7654
			Email: sarah.alexander@sickkids.ca
	Downey
	Southern California Permanente Medical Group
		Robert M Cooper	Ph: 626-564-3455
	Duarte
	City of Hope Comprehensive Cancer Center
		Anna B Pawlowska	Ph: 800-826-4673
			Email: becomingapatient@coh.org
	Loma Linda
	Loma Linda University Cancer Institute at Loma Linda University Medical Center
		Antranik A Bedros	Ph: 909-558-3375
	Long Beach
	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
		Amanda M Termuhlen	Ph: 562-933-5437
	Los Angeles
	Childrens Hospital Los Angeles
		Leo Mascarenhas	Ph: 323-361-4110
	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
		Carole H Hurvitz	Ph: 310-423-8965
	San Diego
	Rady Children's Hospital - San Diego
		William D Roberts	Ph: 858-966-5934
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Christopher C Dvorak	Ph: 877-827-3222
Delaware
	Wilmington
	Alfred I. duPont Hospital for Children
		Christopher N Frantz	Ph: 302-651-5755
District of Columbia
	Washington
	Children's National Medical Center
		Jeffrey S Dome	Ph: 202-884-2549
Florida
	Fort Myers
	Lee Cancer Care of Lee Memorial Health System
		Emad K Salman	Ph: 239-343-5333
	Jacksonville
	Nemours Children's Clinic
		Eric S Sandler	Ph: 904-697-3529
	Orlando
	Nemours Children's Clinic - Orlando
		Ramamoorthy Nagasubramanian	Ph: 407-650-7150
	Pensacola
	Nemours Children's Clinic - Pensacola
		Jeffrey H Schwartz	Ph: 904-697-3529
	Saint Petersburg
	All Children's Hospital
		Gregory A Hale	Ph: 727-767-2423
			Email: HamblinF@allkids.org
Georgia
	Atlanta
	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
		Howard M Katzenstein	Ph: 888-785-1112
	Augusta
	Medical College of Georgia Cancer Center
		Colleen H McDonough	Ph: 706-721-1663
			Email: cancer@georgiahealth.edu
Illinois
	Chicago
	University of Illinois Cancer Center
		Mary L Schmidt	Ph: 312-355-3046
Indiana
	Indianapolis
	Riley's Children Cancer Center at Riley Hospital for Children
		Robert J Fallon	Ph: 317-274-2552
	St. Vincent Indianapolis Hospital
		Bassem I Razzouk	Ph: 317-338-2194
Iowa
	Des Moines
	Blank Children's Hospital
		Wendy L Woods-Swafford	Ph: 888-823-5923
			Email: ctsucontact@westat.com
Kentucky
	Lexington
	University of Kentucky Chandler Medical Center
		Martha F Greenwood	Ph: 859-257-3379
	Louisville
	Kosair Children's Hospital
		Alexandra C Cheerva	Ph: 866-530-5516
Louisiana
	New Orleans
	Ochsner Cancer Institute at Ochsner Clinic Foundation
		Craig Lotterman	Ph: 888-562-4763
	Tulane Cancer Center at Tulane University Hospital and Clinic
		Tammuella C Singleton	Ph: 504-988-6121
Maryland
	Baltimore
	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
		Joseph M Wiley	Ph: 410-601-6120
			Email: pridgely@lifebridgehealth.org
	Greenebaum Cancer Center at University of Maryland Medical Center
		Teresa A York	Ph: 800-888-8823
Michigan
	Lansing
	Breslin Cancer Center at Ingham Regional Medical Center
		Renuka Gera	Ph: 517-334-2765
Minnesota
	Minneapolis
	Children's Hospitals and Clinics of Minnesota - Minneapolis
		Bruce C Bostrom	Ph: 612-813-5193
Mississippi
	Jackson
	University of Mississippi Cancer Clinic
		Gail C Megason	Ph: 601-815-6700
Missouri
	Saint Louis
	David C. Pratt Cancer Center at St. John's Mercy
		Bethany G. Sleckman	Ph: 913-948-5588
Nebraska
	Omaha
	Children's Hospital
		Minnie Abromowitch	Ph: 402-955-3949
	UNMC Eppley Cancer Center at the University of Nebraska Medical Center
		Peter F Coccia	Ph: 800-999-5465
Nevada
	Las Vegas
	CCOP - Nevada Cancer Research Foundation
		Jonathan Bernstein	Ph: 702-384-0013
New Jersey
	Hackensack
	Hackensack University Medical Center Cancer Center
		Steven H Diamond	Ph: 201-996-2879
	New Brunswick
	Saint Peter's University Hospital
		Stanley Calderwood	Ph: 732-745-8600ext6163
			Email: kcovert@saintpetersuh.com
New Mexico
	Albuquerque
	University of New Mexico Cancer Center
		Koh B Boayue	Ph: 505-272-6972
New York
	Bronx
	Montefiore Medical Center
		Rosanna J Ricafort	Ph: 718-904-2730
			Email: aecc@aecom.yu.edu
	Buffalo
	Roswell Park Cancer Institute
		Barbara J Bambach	Ph: 877-275-7724
North Carolina
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		Thomas W McLean	Ph: 336-713-6771
Ohio
	Akron
	Akron Children's Hospital
		Steven J Kuerbitz	Ph: 330-543-3193
	Columbus
	Nationwide Children's Hospital
		Mark A Ranalli	Ph: 614-722-2708
	Dayton
	Dayton Children's - Dayton
		Emmett H Broxson	Ph: 800-228-4055
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Rene Y McNall-Knapp	Ph: 405-271-4272
			Email: julie-traylor@ouhsc.edu
Pennsylvania
	Danville
	Geisinger Cancer Institute at Geisinger Health
		Jeffrey S Taylor	Ph: 570-271-5251
	Philadelphia
	Children's Hospital of Philadelphia
		L. C Bailey	Ph: 215-590-2810
	Pittsburgh
	Children's Hospital of Pittsburgh of UPMC
		Arthur K Ritchey	Ph: 412-692-5573
South Carolina
	Columbia
	Palmetto Health South Carolina Cancer Center
		Ronnie W. Neuberg	Ph: 803-434-3680
South Dakota
	Sioux Falls
	Sanford Cancer Center at Sanford USD Medical Center
		Kayelyn J Wagner	Ph: 605-328-1367
Texas
	Corpus Christi
	Driscoll Children's Hospital
		M. C Johnson	Ph: 361-694-5311
	Dallas
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Naomi J Winick	Ph: 214-648-7097
	Fort Worth
	Cook Children's Medical Center - Fort Worth
		Mary Meaghan P Granger	Ph: 682-885-2103
	San Antonio
	Methodist Children's Hospital of South Texas
		Jaime Estrada	Ph: 210-575-7000
	University of Texas Health Science Center at San Antonio
		Anne-Marie R Langevin	Ph: 210-567-0653
			Email: che@uthscsa.edu
Virginia
	Norfolk
	Children's Hospital of The King's Daughters
		Eric J Lowe	Ph: 757-668-7243
Washington
	Tacoma
	Madigan Army Medical Center - Tacoma
		Melissa A Forouhar	Ph: 253-968-0129
			Email: mamcdci@amedd.army.mil
Wisconsin
	Marshfield
	Marshfield Clinic - Marshfield Center
		Michael J McManus	Ph: 715-389-4457
Canada
Ontario
	Kingston
	Cancer Centre of Southeastern Ontario at Kingston General Hospital
		Mariana P Silva	Ph: 613-544-2630
	Toronto
	Hospital for Sick Children
		Ronald M Grant	Ph: 416-813-7654ext2027
			Email: jason.mcguire@sickkids.ca
Quebec
	Montreal
	Montreal Children's Hospital at McGill University Health Center
		Sharon B Abish	Ph: 514-412-4445
			Email: info@thechildren.com

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01371656
Information obtained from ClinicalTrials.gov on November 25, 2012