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

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