Clinical Trial: Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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)

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 Summary:

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 twi
Sponsor: Children's Oncology Group

Current Primary Outcome: Occurrence of at least 1 episode of true bacteremia among AL and HSCT subjects, respectively [ Time Frame: Up to 60 days ]

Original Primary Outcome: Occurrence of at least 1 episode of true bacteremia during the study timeframe of 2 courses of chemotherapy or 1 transplant procedure among AL and HSCT subjects, respectively

Current Secondary Outcome:

• Susceptibility of E. coli, K. pneumoniae, and P. aeruginosa stool or peri-rectal swab isolates to cefepime, imipenem, and levofloxacin [ Time Frame: Up to 1 year ]
• Susceptibility of S. mitis peri-rectal swab isolates to cefepime, levofloxacin, and penicillin [ Time Frame: Up to 1 year ]
• Presence of carbapenem-resistant Enterobacteriaceae [ Time Frame: Up to 1 year ]
• Resistance patterns for the gastrointestinal isolates colonizing each patient [ Time Frame: Up to 1 year ]
• Resistance patterns of bacterial isolates from all sterile site cultures [ Time Frame: Up to 1 year ]
• Duration of parenteral antibiotic administration [ Time Frame: During 2 courses of chemotherapy or 1 transplantation procedure ]
  Compared between the 2 arms using 2-sample t-test. Wilcoxon rank sum test will also be considered. Estimated using linear regression models.
• Incidence of febrile neutropenia [ Time Frame: Up to 1 year ]
  Compared between arms using the Chi-square test. Evaluated using logistic regression models. Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0.
• Incidence of severe infection [ Time Frame: Up to 1 year ]
  Compared between arms using the Chi-square test. Evaluated using logistic regression models. Graded using the NCI CTCAE v. 4.0.
• Incidence of death from bacterial infection [ Time Frame: Up to 1 year ]
  Compared between arms using the Chi-square test. Evaluated using logistic regression models. Graded using the NCI CTCAE v. 4.0.
• Incidence of musculoskeletal adverse events [ Time Frame: Up to 1 year ]
  Compared between arms using the Chi-square test. Evaluated using logistic regression models. Graded using the NCI CTCAE v. 4.0.
• Incidence of tendinopathy (tendonitis and tendon rupture) [ Time Frame: Up to 1 year ]
  Separate levofloxacin patients into those with/without concurrent steroid use and comparing them separately to control patients, or adjusting for concurrent steroid use as covariate in logistic regression models.
• Incidence of CDAD, defined as a positive C. difficile toxin assay result and diarrhea, CTCAE version 4, grade 2 and higher [ Time Frame: Up to 1 year ]
  Compared by separating levofloxacin patients into those with/without concurrent steroid use or adjusting for concurrent steroid use as a covariate in logistic regression models.

Original Secondary Outcome:

• Susceptibility of E. coli, K. pneumoniae, and P. aeruginosa to cefepime, imipenem, and levofloxacin and the susceptibility of S. mitis to cefepime, levofloxacin, and penicillin at the start and end of each treatment period
• Incidence of febrile neutropenia, severe infection, and death from bacterial infection
• Safety of levofloxacin with special attention to musculoskeletal disorders, particularly tendinopathy and tendon rupture, as assessed by CTCAE v. 4.0 every 6 months for 2 years and annually thereafter
• Duration of parenteral antibiotic administration during 2 courses of chemotherapy or 1 transplantation procedure

Information By: Children's Oncology Group

Dates:
Date Received: June 4, 2011
Date Started: June 2011
Date Completion:
Last Updated: February 13, 2017
Last Verified: February 2017