The purpose of this study is to compare the exposure of febuxostat in pediatric patients (≥6\<18 years of age) and in adults suffering from hematological malignancies at intermediate to high risk of TLS and to compare the effect in terms of serum uric acid levels.
In the FLORET study it is planned to enroll 3 groups of patients in order to receive oral administration (film-coated tablets) of two different dose levels of febuxostat: children (from 6 to less than 12 years of age) will receive two different dose levels respectively; adolescents (from 12 to less than 18 years of age) will receive 80 and 120 mg/day respectively and adults (equal or major than 18 years of age) will receive 120 mg/day. The two dose levels for children and adolescents groups were to be sequentially administered, whereas the groups that will receive the first dose levels will simultaneously start the treatment at the study beginning. The individual treatment duration will be of 7 to 9 days, according to chemotherapy duration, as per Investigator's judgement.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
30
Intervention is orally administered to patients in this arm.
University Hospital Tsaritsa Yoanna
Sofia, Bulgaria
Semmelweis Egyetem (paediatric)
Budapest, Hungary
Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/F)
Apparent clearance of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Time frame: 7 days
PK Parameter: Apparent Volume of Distribution (Vd/F)
Apparent volume of distribution of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Time frame: 7 days
PK Parameter: Absorption Rate Constant (Ka)
Absorption rate constant of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Time frame: 7 days
PK Parameter: Area Under Curve (AUC)
AUC of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Time frame: 7 days
PK Parameter: Maximum Plasma Concentration (Cmax)
Maximum plasma concentration of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Time frame: 7 days
PK Parameter: Tmax
Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Time frame: 7 days
Pharmacodynamic (PD) Parameter: Area Under the Curve of Serum Uric Acid (sUA)
Area under the curve of sUA from baseline (Visit 1, Day 1) to the Evaluation Visit (Visit 8, Day 8) (AUC sUA 1-8)
Time frame: 8 days
Assessment of Laboratory Tumor Lysis Syndrome (LTLS)
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Semmelweis Egyetem
Budapest, Hungary
Debreceni Egyetem Klinikai Központ
Debrecen, Hungary
SOC Oncologia Medica A - Centro di Riferimento Oncologico
Aviano, Pordenone, Italy
Policlinico S. Orsola Malpighi
Bologna, Italy
A.O.U.C. Azienda Ospedaliero - Universitaria Careggi
Florence, Italy
Azienda Ospedaliero Universitaria Meyer
Florence, Italy
Istituto G Gaslini Ospedale Pediatrico IRCCS
Genova, Italy
Azienda Ospedaliero-Universitaria Pisana
Pisa, Italy
...and 7 more locations
Assessment of LTLS at Visit 1 (Day 1) and from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8). LTLS is diagnosed if levels of 2 or more values of uric acid, potassium, phosphate or calcium are more than or less than normal at presentation or if they change by at least 25% from baseline.
Time frame: 7 days
Assessment of Clinical Tumor Lysis Syndrome (CTLS)
Assessment of CTLS at Visit 1 (Day 1) and from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8). CTLS is present when LTLS is accompanied by at least one of the following significant clinical complications: increased creatinine level ≥ 1.5 upper limit of normal, cardiac arrhythmia/sudden death or seizure.
Time frame: 7 days
Assessment of Treatment Emergent Signs and Symptoms (TESS)
Assessment of incidence, severity (through Mild/Moderate/Severe scale), seriousness and treatment-causality of TESS from Screening Visit to End of Study Visit. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. An adverse event was considered as TESS if it occured for the first time or if it worsened in terms of seriousness or severity after first study drug intake.
Time frame: Estimated maximum time frame: 27 days
Assessment of Participants Affected by Treatment Emergent Signs and Symptoms (TESS)
Number of participants affected by TESS from Screening Visit to End of Study Visit.
Time frame: Estimated maximum time frame: 27 days
Performance Status (PS) Evaluation
Quality of life was to be assessed by PS evaluation from Screening Visit to End of Study Visit. The Karnofsky Performance Status (KPS) scale was to be used for patients aged 16 years and older; the Lansky Play Performance Status (LPS) scale was to be used for patients aged less than 16 years. Both scales range from scores of 0 to 100 points at intervals of 10 where 0 points represent the worst outcome (KPS: 0 = death; LPS: 0 = unresponsive) and 100 points the best (KPS: 100 = normal, no complaints, no evidence of disease; LPS: 100 = fully active).
Time frame: Estimated maximum time frame: 27 days