A Phase 3 interventional study of Febuxostat and Allopurinol in Tumor Lysis Syndrome, sponsored by Menarini Group. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-11-03.
Sponsored by Menarini Group · Phase 3, Interventional, and Prevention
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
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.
5,475 studies on the registry are indexed under Leukemia; 629 are open to participants now.
This study's enrollment of 346 is above the median of 38 across 4,268 interventional studies indexed under Leukemia.
Browse Leukemia studies →Menarini Group is the lead sponsor of 28 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Febuxostat for 7-9 days
Drug: Febuxostat
Allopurinol for 7-9 days
Drug: Allopurinol
Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)
Also known as: Adenuric
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)
Also known as: Zyloric
Serum Uric Acid (sUA) Level Control
Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)
Time frame: 8 days
Preservation of Renal Function
Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)
Time frame: 8 days
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
Time frame: 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.
Time frame: 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
Time frame: 6 days
Treatment Emergent Signs or Symptoms (TESS)
Incidence, severity, seriousness and treatment-causality of TESS
Time frame: 14 ± 2 days
First patient in (screening) 01 Oct 2012, last patient out 11 Oct 2013. At 79 sites across 11 European countries (Croatia, Czech Republic, Germany, Hungary, Italy, Poland, Romania, Russia, Serbia, Spain and Ukraine) and Brazil
| Milestone | Febuxostat | Allopurinol |
|---|---|---|
| Started | 173 | 173 |
| Completed | 169 | 170 |
| Not completed | 4 | 3 |
| Withdrew: Death | 3 | 0 |
| Withdrew: Withdrawal by subject | 0 | 2 |
| Withdrew: Protocol violation | 0 | 1 |
| Withdrew: Patient refused to attend last visit | 1 | 0 |
Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)
| mg x hour/dL | Febuxostat | Allopurinol |
|---|---|---|
| Serum Uric Acid (sUA) Level Control | 514.0 ± 225.71 | 708.0 ± 234.42 |
Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)
| change % | Febuxostat | Allopurinol |
|---|---|---|
| Preservation of Renal Function | -0.83 ± 26.977 | -4.92 ± 16.695 |
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
| % of patients who fail to respond | Febuxostat | Allopurinol |
|---|---|---|
| Treatment Responder Rate | 1.7 | 4.0 |
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.
| % of patients with LTLS occurrence | Febuxostat | Allopurinol |
|---|---|---|
| Assessment of Laboratory Tumor Lysis Syndrome (LTLS) | 8.1 | 9.2 |
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
| % of patients with CTLS occurrence | Febuxostat | Allopurinol |
|---|---|---|
| Assessment of Clinical Tumor Lysis Syndrome (CTLS) | 1.7 | 1.2 |
Incidence, severity, seriousness and treatment-causality of TESS
Results for this outcome have not been posted.
Collected over 14 ± 2 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Febuxostat | — | 21/173 (12.1%) | 116/173 (67.1%) |
| Allopurinol | — | 6/173 (3.5%) | 112/173 (64.7%) |
| Event | Febuxostat | Allopurinol |
|---|---|---|
| PneumoniaInfections and infestations | 5/173 | 2/173 |
| Febrile neutropeniaBlood and lymphatic system disorders | 3/173 | 1/173 |
| SepsisInfections and infestations | 3/173 | 0/173 |
| LeukopeniaBlood and lymphatic system disorders | 2/173 | 0/173 |
| Atrial FibrillationCardiac disorders | 2/173 | 0/173 |
| HeadacheNervous system disorders | 2/173 | 0/173 |
| AnaemiaBlood and lymphatic system disorders | 1/173 | 0/173 |
| NeutropeniaBlood and lymphatic system disorders | 1/173 | 1/173 |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/173 | 1/173 |
| Cardiac failure acuteCardiac disorders | 1/173 | 0/173 |
| Event | Febuxostat | Allopurinol |
|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 30/173 | 40/173 |
| AnaemiaBlood and lymphatic system disorders | 38/173 | 25/173 |
| LeukopeniaBlood and lymphatic system disorders | 25/173 | 27/173 |
| ThrombocytopeniaBlood and lymphatic system disorders | 25/173 | 19/173 |
| PyrexiaGeneral disorders | 23/173 | 18/173 |
| NauseaGastrointestinal disorders | 22/173 | 21/173 |
| DiarrhoeaGastrointestinal disorders | 16/173 | 11/173 |
| ConstipationGastrointestinal disorders | 14/173 | 11/173 |
| HeadacheNervous system disorders | 13/173 | 5/173 |
| VomitingGastrointestinal disorders | 10/173 | 12/173 |
| Age, Continuous(years) | Febuxostat | Allopurinol | Total |
|---|---|---|---|
| Mean | 58.5 ± 14.26 | 58.3 ± 13.26 | 58.4 ± 13.75 |
| Sex: Female, Male(Participants) | Febuxostat | Allopurinol | Total |
|---|---|---|---|
| Female | 65 | 67 | 132 |
| Male | 108 | 106 | 214 |
| serum uric acid (sUA)(participants) | Febuxostat | Allopurinol | Total |
|---|---|---|---|
| < or = 7.5 mg/dL | 151 | 152 | 303 |
| > 7.5 mg/dL | 22 | 21 | 43 |
| TLS risk(participants) | Febuxostat | Allopurinol | Total |
|---|---|---|---|
| Intermediate | 143 | 141 | 284 |
| High | 30 | 32 | 62 |
| Type of Hematologic Malignancy(participants) | Febuxostat | Allopurinol | Total |
|---|---|---|---|
| Acute leukemia | 34 | 25 | 59 |
| Chronic lymphocytic leukemia | 80 | 94 | 174 |
| Lymphoma | 59 | 54 | 113 |
No study locations are listed for this record.
This study is completed, as verified in Oct 2014. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Febuxostat