Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies

Tumor Lysis Syndrome Clinical Trial

— FLORENCE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01724528
• Other study ID #: FLO-01
• Secondary ID: 2012-000776-42
• Status: Completed
• Phase: Phase 3
• First received: November 7, 2012
• Last updated: October 27, 2014
• Start date: October 2012
• Est. completion date: October 2013

Study information

• Verified date: October 2014
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesRussia: Ministry of Health of the Russian FederationUkraine: State Pharmacological Center - Ministry of HealthSpain: Agencia Española de Medicamentos y Productos SanitariosBrazil: National Health Surveillance AgencyCroatia: Ministry of Health and Social CareCzech Republic: State Institute for Drug ControlHungary: National Institute of PharmacyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: National Agency for Medicines and Medical DevicesSerbia and Montenegro: Agency for Drugs and Medicinal Devices
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 346
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Syndrome
• Tumor Lysis Syndrome

Intervention

Drug:
• Febuxostat
Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Menarini Group

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Treatment Emergent Signs or Symptoms (TESS)	Incidence, severity, seriousness and treatment-causality of TESS	14 ± 2 days	Yes
Primary	Serum Uric Acid (sUA) Level Control	Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)	8 days	No
Primary	Preservation of Renal Function	Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)	8 days	No
Secondary	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	6 days	No
Secondary	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.	6 days	No
Secondary	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	6 days	No