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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01371656
Other study ID # ACCL0934
Secondary ID NCI-2011-02636CD
Status Completed
Phase Phase 3
First received
Last updated
Start date September 2011
Est. completion date June 2017

Study information

Verified date June 2018
Source Children's Oncology Group
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 624
Est. completion date June 2017
Est. primary completion date June 2017
Accepts healthy volunteers No
Gender All
Age group 6 Months to 21 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
levofloxacin
Given PO or IV

Locations

Country Name City State
Canada McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario
Canada Cancer Centre of Southeastern Ontario at Kingston General Hospital Kingston Ontario
Canada The Montreal Children's Hospital of the MUHC Montreal Quebec
Canada Janeway Child Health Centre Saint John's Newfoundland and Labrador
Canada Hospital for Sick Children Toronto Ontario
Canada CancerCare Manitoba Winnipeg Manitoba
United States Children's Hospital Medical Center of Akron Akron Ohio
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States C S Mott Children's Hospital Ann Arbor Michigan
United States Mission Hospital-Memorial Campus Asheville North Carolina
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Georgia Regents University Augusta Georgia
United States Sinai Hospital of Baltimore Baltimore Maryland
United States Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Floating Hospital for Children at Tufts Medical Center Boston Massachusetts
United States Montefiore Medical Center Bronx New York
United States Roswell Park Cancer Institute Buffalo New York
United States University of Illinois Chicago Illinois
United States Cleveland Clinic Foundation Cleveland Ohio
United States Palmetto Health Richland Columbia South Carolina
United States Nationwide Children's Hospital Columbus Ohio
United States Driscoll Children's Hospital Corpus Christi Texas
United States University of Texas Southwestern Medical Center Dallas Texas
United States Geisinger Medical Center Danville Pennsylvania
United States The Children's Medical Center of Dayton Dayton Ohio
United States Blank Children's Hospital Des Moines Iowa
United States Southern California Permanente Medical Group Downey California
United States City of Hope Medical Center Duarte California
United States Golisano Children's Hospital of Southwest Florida Fort Myers Florida
United States Brooke Army Medical Center Fort Sam Houston Texas
United States Cook Children's Medical Center Fort Worth Texas
United States Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan
United States Hackensack University Medical Center Hackensack New Jersey
United States Connecticut Children's Medical Center Hartford Connecticut
United States Baylor College of Medicine Houston Texas
United States Riley Hospital for Children Indianapolis Indiana
United States Saint Vincent Hospital and Health Services Indianapolis Indiana
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic - Jacksonville Jacksonville Florida
United States Michigan State University - Breslin Cancer Center Lansing Michigan
United States Nevada Cancer Research Foundation CCOP Las Vegas Nevada
United States University of Kentucky Lexington Kentucky
United States Arkansas Children's Hospital Little Rock Arkansas
United States Loma Linda University Medical Center Loma Linda California
United States Miller Children's Hospital Long Beach California
United States Cedars-Sinai Medical Center Los Angeles California
United States Children's Hospital Los Angeles Los Angeles California
United States Kosair Children's Hospital Louisville Kentucky
United States Marshfield Clinic Marshfield Wisconsin
United States Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota
United States Saint Peter's University Hospital New Brunswick New Jersey
United States UMDNJ - Robert Wood Johnson University Hospital New Brunswick New Jersey
United States Children's Hospital-Main Campus New Orleans Louisiana
United States Ochsner Medical Center New Orleans Louisiana
United States Tulane University Health Sciences Center New Orleans Louisiana
United States Columbia University Medical Center New York New York
United States New York University Langone Medical Center New York New York
United States Childrens Hospital-King's Daughters Norfolk Virginia
United States Advocate Children's Hospital-Oak Lawn Oak Lawn Illinois
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Children's Hospital and Medical Center of Omaha Omaha Nebraska
United States University of Nebraska Medical Center Omaha Nebraska
United States Nemours Children's Hospital Orlando Florida
United States Nemours Children's Clinic - Pensacola Pensacola Florida
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania
United States University of Rochester Rochester New York
United States Saint John's Mercy Medical Center Saint Louis Missouri
United States All Children's Hospital Saint Petersburg Florida
United States Methodist Children's Hospital of South Texas San Antonio Texas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States Rady Children's Hospital - San Diego San Diego California
United States University of California San Francisco Medical Center-Parnassus San Francisco California
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington
United States Madigan Army Medical Center Tacoma Washington
United States The Toledo Hospital/Toledo Children's Hospital Toledo Ohio
United States Ny Cancer% Valhalla New York
United States Children's National Medical Center Washington District of Columbia
United States Lombardi Comprehensive Cancer Center at Georgetown University Washington District of Columbia
United States Saint Mary's Hospital West Palm Beach Florida
United States Alfred I duPont Hospital for Children Wilmington Delaware
United States Wake Forest University Health Sciences Winston-Salem North Carolina

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Comparison of the Percentage of Patients Having Bacteremia Incidence Between Levofloxacin vs. No Prophylaxis Arms A bacteremia incidence is defined as an occurrence of at least 1 episode of true (centrally reviewed) bacteremia among Acute Leukemia (AL) and Hematopoietic stem cell transplantation (HSCT) patients. Up to 60 days after enrollment or receiving levofloxacin
Secondary Comparison of the Percentage of Patients Having Antibiotic Exposures Between Arms Exposure to antibiotics was considered during the infection observation period(s) was defined a priori as follows: Gram positive agents = vancomycin, linezolid, daptomycin or quinupristin/dalfopristin; Aminoglycosides = amikacin, gentamicin or tobramycin; Third or fourth generation cephalosporins = cefepime, ceftazidime, ceftriaxone or cefotaxime; Empiric antibiotics for fever and neutropenia = imipenem, meropenem, cefepime, ceftazidime or piperacillin/tazobactam Up to 60 days after enrollment or receiving levofloxacin
Secondary Comparison of the Percentage of Patients Having Incidence of Fever and Febrile Neutropenia Between Arms Fever and febrile neutropenia defined as Absolute Neutrophil Count (ANC) < 1000/mm3 with a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >= 38 degrees C (100.4 degrees F) for more than one hour. Up to 60 days after enrollment or receiving levofloxacin
Secondary Comparison of the Percentage of Patients Having Severe Infection Between Arms Severe infection defined as any grade 4 or 5 CTCAE catheter-related infection, enterocolitis, lung infection, sepsis, small intestine infection and other infections or infestations Up to 60 days after enrollment or receiving levofloxacin
Secondary Comparison of the Percentage of Patients That Died Due to Bacterial Infection Between Arms Up to 60 days after enrollment or receiving levofloxacin
Secondary Comparison of the Percentage of Patients Having Incidence of Musculoskeletal Adverse Events Including Tendinopathy (Tendonitis and Tendon Rupture) Between Arms Musculoskeletal conditions included at least one occurrence of arthralgia, arthritis, gait abnormality or tendinopathy. Enrollment, 2 months and 12 months post infection observation period
Secondary Comparison of the Percentage of Patients Having Incidence of CDAD Between Arms Clostridium Difficile Associated Disease (CDAD) is defined as a positive C. difficile toxin assay result and diarrhea, CTCAE version 4, grade 2 and higher. Up to 60 days after enrollment or receiving levofloxacin
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