Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies (FLORENCE)

• serum uric acid (sUA) level control [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)
  
  
• Preservation of renal function [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)
  
  

• Treatment responder rate [ Time Frame: 6 days ] [ Designated as safety issue: No ]
  Assessment of treatment responder rate, where treatment response is defined as the maintenance of sUA < 7.5 mg/dL from Day 3 to Day 8
  
  
• Assessment of laboratory tumor lysis syndrome (LTLS) [ Time Frame: 6 days ] [ Designated as safety issue: No ]
  Assessment of LTLS, from Day 3 to Day 8. According to Cairo-Bishop definition LTLS is defined by the presence of 2 or more laboratory abnormalities including: a 25% increase or levels above normal for serum uric acid, potassium, and phosphate or a 25% decrease or levels below normal for calcium.
  
  
• Assessment of clinical tumor lysis syndrome (CTLS) [ Time Frame: 6 days ] [ Designated as safety issue: No ]
  Assessment of CTLS, from Day 3 to Day 8. According to Cairo-Bishop definition, CTLS is defined by the presence of LTLS in addition to 1 or more of the following significant clinical complications: renal insufficiency, cardiac arrhythmias, sudden death and seizures. The grade of CTLS is defined by the maximal grade of the clinical manifestation
  
  

• Treatment emergent signs or symptoms (TESS) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  Incidence, severity, seriousness and treatment-causality of TESS
  
  

This study is designed as a randomised, double-blind, active-controlled, parallel-group study to be conducted in approximately 80 sites.

Approximately 340 male or female patients aged 18 or older suffering from hematologic malignancies (de novo patients or relapsing patients) at intermediate to high risk of TLS and scheduled for receiving the first cycle of cytotoxic chemotherapy, regardless of the line of treatment, will be randomized in this study. Eligible patients (as per screening visit) will be randomly allocated in a 1:1 ratio to Febuxostat or Allopurinol. The double-blind treatment period starts two days prior to the planned beginning of chemotherapy and continues for 7 to 9 consecutive days, according to Investigator judgment and on the basis of the actual duration of chemotherapy regimen administered to the patient. Along the study treatment, uric acid levels, creatinine levels, Laboratory TLS/Clinical TLS and Adverse Events represent the major clinical findings to be monitored on a daily basis. Overall the study encompasses 10 to 11 planned visits at site, including screening, randomisation, on treatment and final follow up visits.