Tumor Lysis SyndromePhase 3FLORENCENCT01724528
Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies
A Phase 3 study testing Febuxostat and Allopurinol in people with Tumor Lysis Syndrome, run by Menarini Group.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumor Lysis Syndrome
- What is being tested?
- Febuxostat and Allopurinol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 346 participants
- Where
- No sites listed yet
- Study dates
- Oct 2012to Oct 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official title: Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies: a Randomized, Double Blind, Phase III Study Versus Allopurinol
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
Read the 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
- Being tested
- Febuxostat, Allopurinol
- Keywords
- Febuxostat, Tumor lysis syndrome, leukemia, lymphoma
- Medical subject headings
- Tumor Lysis Syndrome, Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FebuxostatDrug
Also called Adenuric
Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)
AllopurinolDrug
Also called Zyloric
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)
| Study group | Role | What they receive |
|---|---|---|
| Febuxostat | Experimental | Febuxostat for 7-9 days Receives: Drug: Febuxostat |
| Allopurinol | Active comparator | Allopurinol for 7-9 days Receives: Drug: Allopurinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Uric Acid (sUA) Level Control
Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)
Measured: 8 days
Preservation of Renal Function
Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)
Measured: 8 days
Secondary outcomes (3)
Treatment Responder Rate
Assessment of treatment responder rate, where treatment response is defined as the maintenance of sUA ≤ 7.5 mg/dL from Day 3 to Day 8
Measured: 6 days
Assessment of Laboratory Tumor Lysis Syndrome (LTLS)
Assessment of LTLS, from Day 3 to Day 8. According to Cairo-Bishop definition LTLS is defined by the presence of 2 or more laboratory abnormalities including: a 25% increase or levels above normal for serum uric acid, potassium, and phosphate or a 25% decrease or levels below normal for calcium.
Measured: 6 days
Assessment of Clinical Tumor Lysis Syndrome (CTLS)
Assessment of CTLS, from Day 3 to Day 8. According to Cairo-Bishop definition, CTLS is defined by the presence of LTLS in addition to 1 or more of the following significant clinical complications: renal insufficiency, cardiac arrhythmias, sudden death and seizures. The grade of CTLS is defined by the maximal grade of the clinical manifestation
Measured: 6 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2012 (estimated)
- Study startOct 2012
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tumor Lysis SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 346 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menarini Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michele Spina, MD, Principal investigator, Centro Riferimento Oncologico (CRO) National Cancer Institute-Aviano-ItalyAngela Capriati, MD, PhD, Study director, Menarini Ricerche S.p.A. - Florence-Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01724528
- Sponsor's protocol ID
- FLO-01
- Other IDs
- 2012-000776-42
- Acronym
- FLORENCE
- Status last verified
- Oct 2014
- First submitted
- 7 Nov 2012
- Last updated
- 3 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 26216382
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies: a Randomized, Double Blind, Phase III Study Versus Allopurinol
- ClinicalTrials.gov ID
- NCT01724528
- Acronym / sponsor ID
- FLORENCE / FLO-01
- Conditions
- Tumor Lysis Syndrome
- Keywords
- Febuxostat, Tumor lysis syndrome, leukemia, lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 346 participants (actual)
- Lead sponsor
- Menarini GroupIndustry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 9 Nov 2012 (estimated)
- Results
- Posted 3 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Febuxostat | Experimental | Drug: FebuxostatFebuxostat for 7-9 days |
| Allopurinol | Active comparator | Drug: AllopurinolAllopurinol for 7-9 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FebuxostatAlso: AdenuricStandard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion) | Drug | Febuxostat |
| AllopurinolAlso: ZyloricStandard 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) | Drug | Allopurinol |
Primary outcome
Serum Uric Acid (sUA) Level Control
Time frame: 8 days
Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)
Preservation of Renal Function
Time frame: 8 days
Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)
3 secondary outcomes
Treatment Responder Rate
Time frame: 6 days
Assessment of Laboratory Tumor Lysis Syndrome (LTLS)
Time frame: 6 days
Assessment of Clinical Tumor Lysis Syndrome (CTLS)
Time frame: 6 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26216382Spina 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michele Spina, MD principal investigator
Centro Riferimento Oncologico (CRO) National Cancer Institute-Aviano-Italy
Angela Capriati, MD, PhD study director
Menarini Ricerche S.p.A. - Florence-Italy
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Febuxostat and Allopurinol in people with Tumor Lysis Syndrome, run by Menarini Group.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum Uric Acid (sUA) Level Control (time frame: 8 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01724528, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2014.