NCT03605212

Brief Summary

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Feb 2017

Geographic Reach
4 countries

17 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 27, 2017

Completed
1.2 years until next milestone

First Submitted

Initial submission to the registry

May 29, 2018

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 25, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 25, 2018

Completed
5 days until next milestone

First Posted

Study publicly available on registry

July 30, 2018

Completed
2.8 years until next milestone

Results Posted

Study results publicly available

June 3, 2021

Completed
Last Updated

June 3, 2021

Status Verified

January 1, 2019

Enrollment Period

1.4 years

First QC Date

May 29, 2018

Results QC Date

January 27, 2021

Last Update Submit

May 10, 2021

Conditions

Tumor Lysis Syndrome

Keywords

TLSFLO-02Hematological Malignancies

Outcome Measures

Primary Outcomes (6)

  • Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/F)

    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)

    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)

    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)

    AUC of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

    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)

    7 days

  • PK Parameter: Tmax

    Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

    7 days

Secondary Outcomes (6)

  • Pharmacodynamic (PD) Parameter: Area Under the Curve of Serum Uric Acid (sUA)

    8 days

  • Assessment of Laboratory Tumor Lysis Syndrome (LTLS)

    7 days

  • Assessment of Clinical Tumor Lysis Syndrome (CTLS)

    7 days

  • Assessment of Treatment Emergent Signs and Symptoms (TESS)

    Estimated maximum time frame: 27 days

  • Assessment of Participants Affected by Treatment Emergent Signs and Symptoms (TESS)

    Estimated maximum time frame: 27 days

  • +1 more secondary outcomes

Study Arms (5)

Cohort 1

EXPERIMENTAL

Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days

Drug: Febuxostat

Cohort 2

EXPERIMENTAL

Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days

Drug: Febuxostat

Cohort 3

EXPERIMENTAL

Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg)

Drug: Febuxostat

Cohort 4

EXPERIMENTAL

Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg)

Drug: Febuxostat

Adults

ACTIVE COMPARATOR

Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg)

Drug: Febuxostat

Interventions

FebuxostatDRUG

Intervention is orally administered to patients in this arm.

AdultsCohort 1Cohort 2Cohort 3Cohort 4

Eligibility Criteria

Age6 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

University Hospital Tsaritsa Yoanna

Sofia, 1527, Bulgaria

Location

Semmelweis Egyetem (paediatric)

Budapest, 1083, Hungary

Location

Semmelweis Egyetem

Budapest, 1085, Hungary

Location

Debreceni Egyetem Klinikai Központ

Debrecen, 4032, Hungary

Location

SOC Oncologia Medica A - Centro di Riferimento Oncologico

Aviano, Pordenone, 33081, Italy

Location

Policlinico S. Orsola Malpighi

Bologna, 40138, Italy

Location

A.O.U.C. Azienda Ospedaliero - Universitaria Careggi

Florence, 50134, Italy

Location

Azienda Ospedaliero Universitaria Meyer

Florence, 50139, Italy

Location

Istituto G Gaslini Ospedale Pediatrico IRCCS

Genova, 16147, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, 56126, Italy

Location

IRCCS Ospedale Pediatrico Bambino Gesù

Rome, 00165, Italy

Location

Ospedale Infantile Regina Margherita

Torino, 10126, Italy

Location

Azienda Ospedaliera Universitaria Integrata di Verona

Verona, 37126, Italy

Location

Hospital de San Pedro de Alcantara

Cáceres, 10002, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Tumor Lysis SyndromeHematologic Neoplasms

Interventions

Febuxostat

Condition Hierarchy (Ancestors)

Lymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesNeoplasms by SiteNeoplasmsHematologic Diseases

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Limitations and Caveats

Data for all outcome measures were not collected due to the paucity of data in the minor patient population and in agreement with EMA with the exceptions of the secondary outcome Assessment of Treatment Emergent Signs and Symptoms (TESS).

Results Point of Contact

Title
Angela Capriati, MD PhD - Corporate Director Clinical Sciences
Organization
Menarini Group
acapriati@menarini-ricerche.it
+39 055 5680

Study Officials

  • Franco Locatelli, Prof, MD

    IRCCS Ospedale Pediatrico Bambino Gesù, Piazza Sant'Onofrio, 4, 00165 Rome, IT

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 29, 2018

First Posted

July 30, 2018

Study Start

February 27, 2017

Primary Completion

July 25, 2018

Study Completion

July 25, 2018

Last Updated

June 3, 2021

Results First Posted

June 3, 2021

Record last verified: 2019-01

Locations

IT(9)ES(4)HU(3)BU(1)