Febuxostat for Tumor Lysis Syndrome Prevention in Hematological Malignancies of Paediatric Patients and Adults (FLORET)

May 10, 2021 updated by: Menarini Group

Open Label, Multi-centre, Parallel Group Study to Compare the Pharmacokinetics (PK), Pharmacodynamics (PD) and Safety of Febuxostat Between Pediatric Patients (≥6<18 Years of Age) and Adults

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Sofia, Bulgaria, 1527
        • University Hospital Tsaritsa Yoanna
  • Hungary
      • Budapest, Hungary, 1085
        • Semmelweis Egyetem
      • Budapest, Hungary, 1083
        • Semmelweis Egyetem (paediatric)
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont
  • Italy
      • Bologna, Italy, 40138
        • Policlinico S. Orsola Malpighi
      • Firenze, Italy, 50139
        • Azienda Ospedaliero Universitaria Meyer
      • Firenze, Italy, 50134
        • A.O.U.C. Azienda Ospedaliero - Universitaria Careggi
      • Genova, Italy, 16147
        • Istituto G Gaslini Ospedale Pediatrico IRCCS
      • Pisa, Italy, 56126
        • Azienda Ospedaliero-Universitaria Pisana
      • Rome, Italy, 00165
        • IRCCS Ospedale Pediatrico Bambino Gesù
      • Torino, Italy, 10126
        • Ospedale Infantile Regina Margherita
      • Verona, Italy, 37126
        • Azienda Ospedaliera Universitaria Integrata di Verona
    • Pordenone
      • Aviano, Pordenone, Italy, 33081
        • SOC Oncologia Medica A - Centro di Riferimento Oncologico
  • Spain
      • Caceres, Spain, 10002
        • Hospital de San Pedro de Alcantara
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañon
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

male and female children of 6 to less than 12 years of age, adolescents of 12 to less than 18 years of age and adults from 18 years:

  • scheduled for first cytotoxic chemotherapy cycle because of hematologic malignancies
  • and at intermediate or high risk of TLS
  • and with no access to rasburicase

Exclusion Criteria:

  • patients with contraindications as per febuxostat summary of product characteristics
  • patients with severe renal insufficiency
  • patients with severe hepatic insufficiency
  • patients with diagnosis of Laboratory TLS (LTLS) or Clinical TLS (CTLS)

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1
Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days
Drug: Febuxostat
Intervention is orally administered to patients in this arm.
Experimental: Cohort 2
Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days
Drug: Febuxostat
Intervention is orally administered to patients in this arm.
Experimental: Cohort 3
Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg)
Drug: Febuxostat
Intervention is orally administered to patients in this arm.
Experimental: Cohort 4
Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg)
Drug: Febuxostat
Intervention is orally administered to patients in this arm.
Active Comparator: Adults
Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg)
Drug: Febuxostat
Intervention is orally administered to patients in this arm.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/F)
Time Frame: 7 days
Apparent clearance of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
7 days
PK Parameter: Apparent Volume of Distribution (Vd/F)
Time Frame: 7 days
Apparent volume of distribution of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
7 days
PK Parameter: Absorption Rate Constant (Ka)
Time Frame: 7 days
Absorption rate constant of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
7 days
PK Parameter: Area Under Curve (AUC)
Time Frame: 7 days
AUC of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
7 days
PK Parameter: Maximum Plasma Concentration (Cmax)
Time Frame: 7 days
Maximum plasma concentration of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
7 days
PK Parameter: Tmax
Time Frame: 7 days
Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
7 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacodynamic (PD) Parameter: Area Under the Curve of Serum Uric Acid (sUA)
Time Frame: 8 days
Area under the curve of sUA from baseline (Visit 1, Day 1) to the Evaluation Visit (Visit 8, Day 8) (AUC sUA 1-8)
8 days
Assessment of Laboratory Tumor Lysis Syndrome (LTLS)
Time Frame: 7 days
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.
7 days
Assessment of Clinical Tumor Lysis Syndrome (CTLS)
Time Frame: 7 days
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.
7 days
Assessment of Treatment Emergent Signs and Symptoms (TESS)
Time Frame: Estimated maximum time frame: 27 days
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.
Estimated maximum time frame: 27 days
Assessment of Participants Affected by Treatment Emergent Signs and Symptoms (TESS)
Time Frame: Estimated maximum time frame: 27 days
Number of participants affected by TESS from Screening Visit to End of Study Visit.
Estimated maximum time frame: 27 days
Performance Status (PS) Evaluation
Time Frame: Estimated maximum time frame: 27 days
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).
Estimated maximum time frame: 27 days

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Menarini Group

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Franco Locatelli, Prof, MD, IRCCS Ospedale Pediatrico Bambino Gesù, Piazza Sant'Onofrio, 4, 00165 Rome, IT

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 27, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 25, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 25, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 29, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 19, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 30, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 3, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FLO-02
  • 2016-001445-61 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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