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

This study has been completed.
Information provided by (Responsible Party):
Menarini Group Identifier:
First received: November 7, 2012
Last updated: October 27, 2014
Last verified: October 2014
The purpose of this study is to determine whether febuxostat is superior to allopurinol in the prevention of tumor lysis syndrome (TLS) in patients with hematological malignancies at intermediate or high risk of TLS (according to Cairo-Bishop classification) who undergo chemotherapy

Condition Intervention Phase
Tumor Lysis Syndrome Drug: Febuxostat Drug: Allopurinol Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies: a Randomized, Double Blind, Phase III Study Versus Allopurinol

Resource links provided by NLM:

Further study details as provided by Menarini Group:

Primary Outcome Measures:
  • Serum Uric Acid (sUA) Level Control [ Time Frame: 8 days ]
    Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)

  • Preservation of Renal Function [ Time Frame: 8 days ]
    Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)

Secondary Outcome Measures:
  • Treatment Responder Rate [ Time Frame: 6 days ]
    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 ]
    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 ]
    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

Other Outcome Measures:
  • Treatment Emergent Signs or Symptoms (TESS) [ Time Frame: 14 ± 2 days ]
    Incidence, severity, seriousness and treatment-causality of TESS

Enrollment: 346
Study Start Date: October 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Febuxostat
Febuxostat for 7-9 days
Drug: Febuxostat
Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)
Other Name: Adenuric
Active Comparator: Allopurinol
Allopurinol for 7-9 days
Drug: Allopurinol
Standard dose, low dose or high dose (as per investigator's judgement at the time of randomization) from DAY 1 to DAY 7 (can be continued up to DAY 9 at investigator's discretion)
Other Name: Zyloric

Detailed Description:

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients scheduled for first cytotoxic chemotherapy cycle, regardless of the line of treatment, because of hematologic malignancies at intermediate or high risk of TLS (according to the TLS risk stratification, Cairo M et al, British Journal of Haematology, 2010)candidate to Allopurinol treatment or have no access to Rasburicase
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3
  • Life expectancy > 1 month

Exclusion Criteria:

  • Patients known to be hypersensitive to Febuxostat or Allopurinol or to any of the components of the formulations
  • Patients with sUA levels ≥ 10 mg/dL at randomization
  • Patients receiving Febuxostat, Allopurinol or any other urate lowering therapy (e.g. Rasburicase, probenecid) within 30 days prior to randomization
  • Patients with severe renal and/or hepatic insufficiency
  • Patients with diagnosis of LTLS or CTLS at randomization
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01724528

Sponsors and Collaborators
Menarini Group
Principal Investigator: Michele Spina, MD Centro Riferimento Oncologico (CRO) National Cancer Institute-Aviano-Italy
Study Director: Angela Capriati, MD, PhD Menarini Ricerche S.p.A. - Florence-Italy
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Menarini Group Identifier: NCT01724528     History of Changes
Other Study ID Numbers: FLO-01
2012-000776-42 ( EudraCT Number )
Study First Received: November 7, 2012
Results First Received: October 27, 2014
Last Updated: October 27, 2014

Keywords provided by Menarini Group:
Febuxostat, Tumor lysis syndrome, leukemia, lymphoma

Additional relevant MeSH terms:
Tumor Lysis Syndrome
Pathologic Processes
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Free Radical Scavengers
Protective Agents
Physiological Effects of Drugs processed this record on August 18, 2017