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

October 27, 2014 updated by: Menarini Group

Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies: a Randomized, Double Blind, Phase III Study Versus Allopurinol

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

346

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Zyloric

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
6 days
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.
6 days
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
6 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment Emergent Signs or Symptoms (TESS)
Time Frame: 14 ± 2 days
Incidence, severity, seriousness and treatment-causality of TESS
14 ± 2 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

October 1, 2013

Study Registration Dates

First Submitted

November 7, 2012

First Submitted That Met QC Criteria

November 7, 2012

First Posted (Estimate)

November 9, 2012

Study Record Updates

Last Update Posted (Estimate)

November 2, 2014

Last Update Submitted That Met QC Criteria

October 27, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FLO-01
  • 2012-000776-42 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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