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