Clinical trial NCT01724528: Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies
Official title: Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies: a Randomized, Double Blind, Phase III Study Versus Allopurinol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tumor Lysis Syndrome
Keywords: Febuxostat, Tumor lysis syndrome, leukemia, lymphoma
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2012-11-09
Enrollment: 346
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Serum Uric Acid (sUA) Level Control
timeFrame: 8 days
measure: Preservation of Renal Function
timeFrame: 8 days
Secondary outcomes:
measure: Treatment Responder Rate
timeFrame: 6 days
measure: Assessment of Laboratory Tumor Lysis Syndrome (LTLS)
timeFrame: 6 days
measure: Assessment of Clinical Tumor Lysis Syndrome (CTLS)
timeFrame: 6 days
Other outcomes:
measure: Treatment Emergent Signs or Symptoms (TESS)
timeFrame: 14 ± 2 days
Locations:
Study officials:
affiliation: Centro Riferimento Oncologico (CRO) National Cancer Institute-Aviano-Italy
name: Michele Spina, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Menarini Ricerche S.p.A. - Florence-Italy
name: Angela Capriati, MD, PhD
role: STUDY_DIRECTOR
References:
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.