RATIONALE: Levofloxacin may be effective in reducing fever and controlling other symptoms of neutropenia in patients who are being treated for cancer. It is not yet known whether levofloxacin is more effective than cefepime in reducing fever and controlling symptoms of neutropenia. PURPOSE: Randomized phase III trial to compare the effectiveness of levofloxacin with that of cefepime in reducing fever and controlling symptoms of neutropenia in patients who are being treated for cancer.

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma Eye Cancer	Drug: cefepime  Drug: levofloxacin	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the safety and efficacy of levofloxacin versus cefepime in cancer patients with fever and neutropenia. II. Compare the percentage of patients whose fever defervesces and who have no signs or symptoms of infection with and without therapeutic modification. III. Compare the percentage of survival of patients treated with these 2 regimens with no therapeutic modifications. IV. Compare the overall survival of patients treated with these 2 regimens regardless of therapeutic modifications. V. Compare the time to resolution of fever in patients treated with these regimens. VI. Compare the microbiologic response by pathogen and site of infection in patients treated with these regimens. VII. Compare the percentage of patients whose fever defervesces only after resolution of neutropenia (absolute neutrophil count at least 500/mm3) with no therapeutic modification.

PROTOCOL OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to type of malignancy (solid tumor, including lymphoma vs leukemia), prior prophylactic antibiotics (yes vs no), and participating center. Patients are randomized to one of two treatment arms. Arm I: Patients receive levofloxacin IV over 90 minutes once daily for 14-28 days. Arm II: Patients receive cefepime IV over 30 minutes every 8 hours for 14-28 days. Patients may receive additional antifungal, antibacterial, or antiviral therapy if condition has deteriorated, no response is seen in 72 hours, or and infection is suspected or documented. Patients are followed at 1-3 and 7-12 days and then at 3-4 weeks.

PROJECTED ACCRUAL: Approximately 260-400 patients (130-200 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of malignancy; Solid tumor (including lymphoma) or leukemia
• Hospitalized and anticipated to remain hospitalized during study
• Febrile defined as oral temperature of at least 100.4 degrees F (38 degrees C) on 2 occasions within 24 hours OR at least 100.8 degrees F (38.2 degrees C) on a single reading; No obvious noninfectious cause of fever (e.g., platelet transfusion)
• Neutropenic, defined as absolute neutrophil count (ANC) currently less than 500/mm3 OR anticipated to be less than 500/mm3 within 24 hours of study entry; Anticipated ANC to be less than 500/mm3 for at least 72 hours; No neutropenia unassociated with malignancy; No chronic neutropenia; No neutropenia anticipated to last more than 14 days
• No acute myelogenous leukemia unless receiving consolidation chemotherapy or induction dose that does not prolong neutropenia for more than 3 weeks
• No infection due to an identified organism
• No high likelihood of infection due to anaerobic organisms, including intra-abdominal infections or perirectal abscess at admission
• No known osteomyelitis
• No requirement for new antifungal agent

--Prior/Concurrent Therapy--

• Biologic therapy: No prior sargramostim (GM-CSF) or filgrastim (G-CSF) for current course of chemotherapy; Concurrent GM-CSF or G-CSF allowed if neutropenia lasts at least 3 days
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified
• Other: No prior treatment under this protocol; No prior prophylactic anti-infectives other than acyclovir or sulfamethoxazole with trimethoprim; At least 72 hours since prior systemic antibiotics (except prophylactic sulfamethoxazole with trimethoprim); At least 30 days since prior experimental drug or medical device (except drugs currently marketed in the United States for the treatment of the malignancy); No other concurrent systemic antibacterial agents; No concurrent topical antimicrobial agents

--Patient Characteristics--

• Age: 18 and over
• Performance status: Not specified
• Life expectancy: At least 14 days
• Hematopoietic: See Disease Characteristics
• Hepatic: Not specified
• Renal: Creatinine clearance at least 20 mL/min; No oliguria (urine output less than 20 mL/hour) unresponsive to fluid challenge
• Cardiovascular: No shock or hypotension (supine systolic blood pressure less than 80 mmHg) unresponsive to fluid challenge
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No HIV infection with CD4 counts less than 200/mm3; No significant risk for seizures; No unstable psychiatric disorder; Weight greater than 40 kg; No prior allergic or severe adverse reaction to study drugs or to any member of the quinolone or beta-lactam class of antibacterials; No disorder or disease that would preclude study

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States

Study chairs or principal investigators

Mary Carol Territo,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068726; UCLA-0006093; NCI-G01-1965; MCNEIL-CAPSS-118
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  July 11, 2001
ClinicalTrials.gov Identifier:  NCT00020865
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08