Clinical trial NCT01371656: Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
Official title: A Randomized Trial of Levofloxacin to Prevent Bacteremia in Children Being Treated for Acute Leukemia (AL) or Undergoing Hematopoietic Stem Cell Transplantation (HSCT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Leukemias of Ambiguous Lineage
Bacterial Infection
Diarrhea
Fungal Infection
Musculoskeletal Complications
Neutropenia
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-06-13
Enrollment: 624
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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

Detailed description: PRIMARY OBJECTIVES:

I. 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 OBJECTIVES:

I. 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 Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Streptococcus mitis.

II. 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.

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

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

V. 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: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive levofloxacin orally (PO) or intravenously (IV) over 60-90 minutes once daily (QD) or twice daily (BID) beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

ARM II: Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.

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

Eligibility criteria: Inclusion Criteria:

* Patient must fit 1 of the following 2 categories:

  * Chemotherapy patients

    * Planned to receive at least 2 consecutive cycles (not required to be the first 2 cycles) of intensive chemotherapy for either:

      * De novo, relapsed or secondary acute myeloid leukemia (AML), or acute leukemia of ambiguous lineage treated with standard AML therapy
      * 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; examples include, but are not limited to, treatment with "4-drug induction" (anthracycline, vincristine, asparaginase, and steroid), high dose cytarabine, anthracycline/cytarabine, ifosfamide/etoposide, and clofarabine-containing regimens
  * Stem cell transplantation patients

    * Planned to receive at least 1 myeloablative autologous or allogeneic 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
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \> 70 mL/min/1.73 m\^2 OR serum creatinine based on age/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)/1.4 mg/dL (female) (13 to \< 16 years of age)
  * 1.7 mg/dL (male)/1.4 mg/dL (female) (\>= 16 years of age)
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

* Patients previously enrolled on the trial are not eligible; therefore, patients with AL who were on study during intensive chemotherapy are not eligible to be enrolled during the HSCT
* Patients with an allergy to quinolones
* Patients with chronic active arthritis
* Patients with a known pathologic prolongation of the corrected QT (QTc)
* Females who are pregnant or breast feeding
* Patients being treated with antibacterial agents, other than any of the following:

  * Cotrimoxazole or other agents including dapsone, atovaquone, and pentamidine administered for Pneumocystitis jiroveci (PCP) prophylaxis
  * Topical antibiotics
  * Central venous catheter antibiotic lock therapy
  * Note: prophylactic antifungal therapy is NOT an exclusion criterion
* Patients currently enrolled on the ACCL1034 study are not eligible until they have completed the 90 day observation period of that study

Primary outcomes:
measure: Comparison of the Percentage of Patients Having Bacteremia Incidence Between Levofloxacin vs. No Prophylaxis Arms
timeFrame: Up to 60 days after enrollment or receiving levofloxacin
Secondary outcomes:
measure: Comparison of the Percentage of Patients Having Antibiotic Exposures Between Arms
timeFrame: Up to 60 days after enrollment or receiving levofloxacin
measure: Comparison of the Percentage of Patients Having Incidence of Fever and Febrile Neutropenia Between Arms
timeFrame: Up to 60 days after enrollment or receiving levofloxacin
measure: Comparison of the Percentage of Patients Having Severe Infection Between Arms
timeFrame: Up to 60 days after enrollment or receiving levofloxacin
measure: Comparison of the Percentage of Patients That Died Due to Bacterial Infection Between Arms
timeFrame: Up to 60 days after enrollment or receiving levofloxacin
measure: Comparison of the Percentage of Patients Having Incidence of Musculoskeletal Adverse Events Including Tendinopathy (Tendonitis and Tendon Rupture) Between Arms
timeFrame: Enrollment, 2 months and 12 months post infection observation period
measure: Comparison of the Percentage of Patients Having Incidence of CDAD Between Arms
timeFrame: Up to 60 days after enrollment or receiving levofloxacin
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Downey
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Long Beach
country: United States
facility: Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center-Parnassus
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University
state: District of Columbia
city: Fort Myers
country: United States
facility: Golisano Children's Hospital of Southwest Florida
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic - Jacksonville
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic - Pensacola
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: West Palm Beach
country: United States
facility: Saint Mary's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Children's Hospital-Oak Lawn
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Services
state: Indiana
city: Des Moines
country: United States
facility: Blank Children's Hospital
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Children's Hospital-Main Campus
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Boston
country: United States
facility: Floating Hospital for Children at Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital at Spectrum Health
state: Michigan
city: Lansing
country: United States
facility: Michigan State University - Breslin Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Saint John's Mercy Medical Center
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital and Medical Center of Omaha
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation CCOP
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: UMDNJ - Robert Wood Johnson University Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Valhalla
country: United States
facility: Ny Cancer%
state: New York
city: Asheville
country: United States
facility: Mission Hospital-Memorial Campus
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: The Children's Medical Center of Dayton
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital/Toledo Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Bethlehem
country: United States
facility: Lehigh Valley Hospital - Muhlenberg
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Norfolk
country: United States
facility: Childrens Hospital-King's Daughters
state: Virginia
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John's
country: Canada
facility: Janeway Child Health Centre
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: The Montreal Children's Hospital of the MUHC
state: Quebec
Study officials:
affiliation: Children's Oncology Group
name: Sarah Alexander, MD
role: PRINCIPAL_INVESTIGATOR
References: