Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies (FLORENCE)
Primary Purpose
Tumor Lysis Syndrome
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Febuxostat
Allopurinol
Sponsored by
About this trial
This is an interventional prevention trial for Tumor Lysis Syndrome focused on measuring Febuxostat, Tumor lysis syndrome, leukemia, lymphoma
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Febuxostat
Allopurinol
Arm Description
Febuxostat for 7-9 days
Allopurinol for 7-9 days
Outcomes
Primary Outcome Measures
Serum Uric Acid (sUA) Level Control
Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)
Preservation of Renal Function
Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)
Secondary Outcome Measures
Treatment Responder Rate
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)
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)
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01724528
Brief Title
Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies
Acronym
FLORENCE
Official Title
Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies: a Randomized, Double Blind, Phase III Study Versus Allopurinol
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Menarini Group
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tumor Lysis Syndrome
Keywords
Febuxostat, Tumor lysis syndrome, leukemia, lymphoma
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
346 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Febuxostat
Arm Type
Experimental
Arm Description
Febuxostat for 7-9 days
Arm Title
Allopurinol
Arm Type
Active Comparator
Arm Description
Allopurinol for 7-9 days
Intervention Type
Drug
Intervention Name(s)
Febuxostat
Other Intervention Name(s)
Adenuric
Intervention Description
Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Other Intervention Name(s)
Zyloric
Intervention Description
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)
Primary Outcome Measure Information:
Title
Serum Uric Acid (sUA) Level Control
Description
Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)
Time Frame
8 days
Title
Preservation of Renal Function
Description
Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)
Time Frame
8 days
Secondary Outcome Measure Information:
Title
Treatment Responder Rate
Description
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
Time Frame
6 days
Title
Assessment of Laboratory Tumor Lysis Syndrome (LTLS)
Description
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.
Time Frame
6 days
Title
Assessment of Clinical Tumor Lysis Syndrome (CTLS)
Description
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
Time Frame
6 days
Other Pre-specified Outcome Measures:
Title
Treatment Emergent Signs or Symptoms (TESS)
Description
Incidence, severity, seriousness and treatment-causality of TESS
Time Frame
14 ± 2 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michele Spina, MD
Organizational Affiliation
Centro Riferimento Oncologico (CRO) National Cancer Institute-Aviano-Italy
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Angela Capriati, MD, PhD
Organizational Affiliation
Menarini Ricerche S.p.A. - Florence-Italy
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
26216382
Citation
Spina M, Nagy Z, Ribera JM, Federico M, Aurer I, Jordan K, Borsaru G, Pristupa AS, Bosi A, Grosicki S, Glushko NL, Ristic D, Jakucs J, Montesinos P, Mayer J, Rego EM, Baldini S, Scartoni S, Capriati A, Maggi CA, Simonelli C; FLORENCE Study Group. FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk. Ann Oncol. 2015 Oct;26(10):2155-61. doi: 10.1093/annonc/mdv317. Epub 2015 Jul 27.
Results Reference
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Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies
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