Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies

NCT ID: NCT01724528

Last Updated: 2014-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 346 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2013-10-31

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.

Conditions

Tumor Lysis Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Febuxostat

Febuxostat for 7-9 days

Group Type: EXPERIMENTAL

Febuxostat

Intervention Type: DRUG

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

Allopurinol

Allopurinol for 7-9 days

Group Type: ACTIVE_COMPARATOR

Allopurinol

Intervention Type: DRUG

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)

Interventions

Febuxostat

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

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)

Intervention Type: DRUG

Other Intervention Names

Adenuric; Zyloric

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Menarini Group

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michele Spina, MD

Role: PRINCIPAL_INVESTIGATOR

Centro Riferimento Oncologico (CRO) National Cancer Institute-Aviano-Italy

Angela Capriati, MD, PhD

Role: STUDY_DIRECTOR

Menarini Ricerche S.p.A. - Florence-Italy

References

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.

Reference Type: DERIVED

PMID: 26216382 (View on PubMed)

Other Identifiers

2012-000776-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FLO-01

Identifier Type: -

Identifier Source: org_study_id