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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Menarini Group
ClinicalTrials.gov Identifier:
NCT01724528
First received: November 7, 2012
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 ] [ 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)


Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • Treatment emergent signs or symptoms (TESS) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ClinicalTrials.gov identifier: NCT01724528

Sponsors and Collaborators
Menarini Group
Investigators
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

No publications provided

Responsible Party: Menarini Group
ClinicalTrials.gov Identifier: NCT01724528     History of Changes
Other Study ID Numbers: FLO-01, 2012-000776-42
Study First Received: November 7, 2012
Last Updated: February 12, 2014
Health Authority: Italy: The Italian Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Russia: Ministry of Health of the Russian Federation
Ukraine: State Pharmacological Center - Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Brazil: National Health Surveillance Agency
Croatia: Ministry of Health and Social Care
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Serbia and Montenegro: Agency for Drugs and Medicinal Devices

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

Additional relevant MeSH terms:
Tumor Lysis Syndrome
Hematologic Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Neoplasms
Hematologic Diseases
Allopurinol
Febuxostat
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Antimetabolites
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014