<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01724528</url>
  </required_header>
  <id_info>
    <org_study_id>FLO-01</org_study_id>
    <secondary_id>2012-000776-42</secondary_id>
    <nct_id>NCT01724528</nct_id>
  </id_info>
  <brief_title>Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies</brief_title>
  <acronym>FLORENCE</acronym>
  <official_title>Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies: a Randomized, Double Blind, Phase III Study Versus Allopurinol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Menarini Group</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Menarini Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether febuxostat is superior to allopurinol in&#xD;
      the prevention of tumor lysis syndrome (TLS) in patients with hematological malignancies at&#xD;
      intermediate or high risk of TLS (according to Cairo-Bishop classification) who undergo&#xD;
      chemotherapy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is designed as a randomised, double-blind, active-controlled, parallel-group study&#xD;
      to be conducted in approximately 80 sites.&#xD;
&#xD;
      Approximately 340 male or female patients aged 18 or older suffering from hematologic&#xD;
      malignancies (de novo patients or relapsing patients) at intermediate to high risk of TLS and&#xD;
      scheduled for receiving the first cycle of cytotoxic chemotherapy, regardless of the line of&#xD;
      treatment, will be randomized in this study. Eligible patients (as per screening visit) will&#xD;
      be randomly allocated in a 1:1 ratio to Febuxostat or Allopurinol. The double-blind treatment&#xD;
      period starts two days prior to the planned beginning of chemotherapy and continues for 7 to&#xD;
      9 consecutive days, according to Investigator judgment and on the basis of the actual&#xD;
      duration of chemotherapy regimen administered to the patient. Along the study treatment, uric&#xD;
      acid levels, creatinine levels, Laboratory TLS/Clinical TLS and Adverse Events represent the&#xD;
      major clinical findings to be monitored on a daily basis. Overall the study encompasses 10 to&#xD;
      11 planned visits at site, including screening, randomisation, on treatment and final follow&#xD;
      up visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Serum Uric Acid (sUA) Level Control</measure>
    <time_frame>8 days</time_frame>
    <description>Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Preservation of Renal Function</measure>
    <time_frame>8 days</time_frame>
    <description>Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment Responder Rate</measure>
    <time_frame>6 days</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Laboratory Tumor Lysis Syndrome (LTLS)</measure>
    <time_frame>6 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Clinical Tumor Lysis Syndrome (CTLS)</measure>
    <time_frame>6 days</time_frame>
    <description>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</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Treatment Emergent Signs or Symptoms (TESS)</measure>
    <time_frame>14 ± 2 days</time_frame>
    <description>Incidence, severity, seriousness and treatment-causality of TESS</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">346</enrollment>
  <condition>Tumor Lysis Syndrome</condition>
  <arm_group>
    <arm_group_label>Febuxostat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Febuxostat for 7-9 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Allopurinol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Allopurinol for 7-9 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Febuxostat</intervention_name>
    <description>Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)</description>
    <arm_group_label>Febuxostat</arm_group_label>
    <other_name>Adenuric</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Allopurinol</intervention_name>
    <description>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)</description>
    <arm_group_label>Allopurinol</arm_group_label>
    <other_name>Zyloric</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients scheduled for first cytotoxic chemotherapy cycle, regardless of the line of&#xD;
             treatment, because of hematologic malignancies at intermediate or high risk of TLS&#xD;
             (according to the TLS risk stratification, Cairo M et al, British Journal of&#xD;
             Haematology, 2010)candidate to Allopurinol treatment or have no access to Rasburicase&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3&#xD;
&#xD;
          -  Life expectancy &gt; 1 month&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients known to be hypersensitive to Febuxostat or Allopurinol or to any of the&#xD;
             components of the formulations&#xD;
&#xD;
          -  Patients with sUA levels ≥ 10 mg/dL at randomization&#xD;
&#xD;
          -  Patients receiving Febuxostat, Allopurinol or any other urate lowering therapy (e.g.&#xD;
             Rasburicase, probenecid) within 30 days prior to randomization&#xD;
&#xD;
          -  Patients with severe renal and/or hepatic insufficiency&#xD;
&#xD;
          -  Patients with diagnosis of LTLS or CTLS at randomization&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michele Spina, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centro Riferimento Oncologico (CRO) National Cancer Institute-Aviano-Italy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Angela Capriati, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Menarini Ricerche S.p.A. - Florence-Italy</affiliation>
  </overall_official>
  <removed_countries>
    <country>Italy</country>
  </removed_countries>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>November 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 9, 2012</study_first_posted>
  <results_first_submitted>October 27, 2014</results_first_submitted>
  <results_first_submitted_qc>October 27, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 2, 2014</results_first_posted>
  <last_update_submitted>October 27, 2014</last_update_submitted>
  <last_update_submitted_qc>October 27, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 2, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Febuxostat, Tumor lysis syndrome, leukemia, lymphoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hematologic Neoplasms</mesh_term>
    <mesh_term>Tumor Lysis Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Allopurinol</mesh_term>
    <mesh_term>Febuxostat</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>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</recruitment_details>
      <pre_assignment_details>Subjects complying with inclusion/exclusion criteria were to be randomised to receive (blinded) standard, low or high dose of study treatment as per investigator's assessment (mainly based on renal function). Randomization was balanced by TLS risk and serum uric acid levels (≤ or &gt; 7.5 mg/dL)</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Febuxostat</title>
          <description>Febuxostat for 7-9 days&#xD;
Febuxostat: Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)</description>
        </group>
        <group group_id="P2">
          <title>Allopurinol</title>
          <description>Allopurinol for 7-9 days&#xD;
Allopurinol: 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)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="173"/>
                <participants group_id="P2" count="173"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="169"/>
                <participants group_id="P2" count="170"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient refused to attend last visit</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Febuxostat</title>
          <description>Febuxostat for 7-9 days&#xD;
Febuxostat: Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)</description>
        </group>
        <group group_id="B2">
          <title>Allopurinol</title>
          <description>Allopurinol for 7-9 days&#xD;
Allopurinol: 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)</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="173"/>
            <count group_id="B2" value="173"/>
            <count group_id="B3" value="346"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.5" spread="14.26"/>
                    <measurement group_id="B2" value="58.3" spread="13.26"/>
                    <measurement group_id="B3" value="58.4" spread="13.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="132"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="108"/>
                    <measurement group_id="B2" value="106"/>
                    <measurement group_id="B3" value="214"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>serum uric acid (sUA)</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt; or = 7.5 mg/dL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="151"/>
                    <measurement group_id="B2" value="152"/>
                    <measurement group_id="B3" value="303"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt; 7.5 mg/dL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>TLS risk</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Intermediate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="143"/>
                    <measurement group_id="B2" value="141"/>
                    <measurement group_id="B3" value="284"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>High</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Type of Hematologic Malignancy</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Acute leukemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chronic lymphocytic leukemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="80"/>
                    <measurement group_id="B2" value="94"/>
                    <measurement group_id="B3" value="174"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphoma</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59"/>
                    <measurement group_id="B2" value="54"/>
                    <measurement group_id="B3" value="113"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Serum Uric Acid (sUA) Level Control</title>
        <description>Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)</description>
        <time_frame>8 days</time_frame>
        <population>Intention to treat (ITT), defined as all randomized patients. Sample size calculation: at least an absolute reduction of 100 mg x h/dL for the AUCsUA1-8 in favour of febuxostat; 340 patients were sufficient to achieve approximately 80% power. Imputation method: last observation carried forward (LOCF); missing baseline values were not replaced.</population>
        <group_list>
          <group group_id="O1">
            <title>Febuxostat</title>
            <description>Febuxostat for 7-9 days&#xD;
Febuxostat: Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)</description>
          </group>
          <group group_id="O2">
            <title>Allopurinol</title>
            <description>Allopurinol for 7-9 days&#xD;
Allopurinol: 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)</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Uric Acid (sUA) Level Control</title>
          <description>Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)</description>
          <population>Intention to treat (ITT), defined as all randomized patients. Sample size calculation: at least an absolute reduction of 100 mg x h/dL for the AUCsUA1-8 in favour of febuxostat; 340 patients were sufficient to achieve approximately 80% power. Imputation method: last observation carried forward (LOCF); missing baseline values were not replaced.</population>
          <units>mg x hour/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="172"/>
                <count group_id="O2" value="172"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="514.0" spread="225.71"/>
                    <measurement group_id="O2" value="708.0" spread="234.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Treatment, TLS risk (intermediate/high) and sUA level at baseline (≤ 7.5 mg/dL and &gt; 7.5 mg/dL) were inserted in the ANCOVA model as covariates</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <param_type>Least squares means difference</param_type>
            <param_value>-196.794</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-238.600</ci_lower_limit>
            <ci_upper_limit>-154.988</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Preservation of Renal Function</title>
        <description>Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)</description>
        <time_frame>8 days</time_frame>
        <population>ITT. Sample size calculation: no change in mean serum creatinine level from baseline to the end of treatment for febuxostat group while allopurinol has a increase of 13%; 340 patients were sufficient to achieve approximately 80% power. Imputation method: LOCF; missing baseline values were not replaced</population>
        <group_list>
          <group group_id="O1">
            <title>Febuxostat</title>
            <description>Febuxostat for 7-9 days&#xD;
Febuxostat: Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)</description>
          </group>
          <group group_id="O2">
            <title>Allopurinol</title>
            <description>Allopurinol for 7-9 days&#xD;
Allopurinol: 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)</description>
          </group>
        </group_list>
        <measure>
          <title>Preservation of Renal Function</title>
          <description>Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)</description>
          <population>ITT. Sample size calculation: no change in mean serum creatinine level from baseline to the end of treatment for febuxostat group while allopurinol has a increase of 13%; 340 patients were sufficient to achieve approximately 80% power. Imputation method: LOCF; missing baseline values were not replaced</population>
          <units>change %</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="173"/>
                <count group_id="O2" value="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.83" spread="26.977"/>
                    <measurement group_id="O2" value="-4.92" spread="16.695"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Treatment, TLS risk (intermediate/high) and sUA level at baseline (≤ 7.5 mg/dL and &gt; 7.5 mg/dL) were inserted in the ANCOVA model as covariates</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0903</p_value>
            <method>ANCOVA</method>
            <param_type>Least squares means difference</param_type>
            <param_value>4.0970</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.6467</ci_lower_limit>
            <ci_upper_limit>8.8406</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment Responder Rate</title>
        <description>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</description>
        <time_frame>6 days</time_frame>
        <population>Intention to Treat (ITT; no imputation applied</population>
        <group_list>
          <group group_id="O1">
            <title>Febuxostat</title>
            <description>Febuxostat for 7-9 days&#xD;
Febuxostat: Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)</description>
          </group>
          <group group_id="O2">
            <title>Allopurinol</title>
            <description>Allopurinol for 7-9 days&#xD;
Allopurinol: 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)</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Responder Rate</title>
          <description>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</description>
          <population>Intention to Treat (ITT; no imputation applied</population>
          <units>% of patients who fail to respond</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="173"/>
                <count group_id="O2" value="173"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7"/>
                    <measurement group_id="O2" value="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1993</p_value>
            <method>Wilson's confidence interval</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>0.0231</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0153</ci_lower_limit>
            <ci_upper_limit>0.0654</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Assessment of Laboratory Tumor Lysis Syndrome (LTLS)</title>
        <description>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.</description>
        <time_frame>6 days</time_frame>
        <population>ITT; no imputation applied</population>
        <group_list>
          <group group_id="O1">
            <title>Febuxostat</title>
            <description>Febuxostat for 7-9 days&#xD;
Febuxostat: Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)</description>
          </group>
          <group group_id="O2">
            <title>Allopurinol</title>
            <description>Allopurinol for 7-9 days&#xD;
Allopurinol: 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)</description>
          </group>
        </group_list>
        <measure>
          <title>Assessment of Laboratory Tumor Lysis Syndrome (LTLS)</title>
          <description>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.</description>
          <population>ITT; no imputation applied</population>
          <units>% of patients with LTLS occurrence</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="173"/>
                <count group_id="O2" value="173"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1"/>
                    <measurement group_id="O2" value="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.8488</p_value>
            <method>Chi-squared</method>
            <param_type>Relative risk</param_type>
            <param_value>0.875</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.4408</ci_lower_limit>
            <ci_upper_limit>1.7369</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Assessment of Clinical Tumor Lysis Syndrome (CTLS)</title>
        <description>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</description>
        <time_frame>6 days</time_frame>
        <population>ITT; no imputation applied</population>
        <group_list>
          <group group_id="O1">
            <title>Febuxostat</title>
            <description>Febuxostat for 7-9 days&#xD;
Febuxostat: Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)</description>
          </group>
          <group group_id="O2">
            <title>Allopurinol</title>
            <description>Allopurinol for 7-9 days&#xD;
Allopurinol: 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)</description>
          </group>
        </group_list>
        <measure>
          <title>Assessment of Clinical Tumor Lysis Syndrome (CTLS)</title>
          <description>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</description>
          <population>ITT; no imputation applied</population>
          <units>% of patients with CTLS occurrence</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="173"/>
                <count group_id="O2" value="173"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7"/>
                    <measurement group_id="O2" value="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>1.0000</p_value>
            <method>Chi-squared</method>
            <param_type>Relative risk</param_type>
            <param_value>0.994</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.9691</ci_lower_limit>
            <ci_upper_limit>1.0199</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Treatment Emergent Signs or Symptoms (TESS)</title>
        <description>Incidence, severity, seriousness and treatment-causality of TESS</description>
        <time_frame>14 ± 2 days</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>14 ± 2 days</time_frame>
      <desc>Analysed for the Safety Population (all patients who received the study drug)</desc>
      <group_list>
        <group group_id="E1">
          <title>Febuxostat</title>
          <description>Febuxostat for 7-9 days&#xD;
Febuxostat: Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)</description>
        </group>
        <group group_id="E2">
          <title>Allopurinol</title>
          <description>Allopurinol for 7-9 days&#xD;
Allopurinol: 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)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="173"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="173"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Hypovolaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Tumour lysis syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral ischaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="116" subjects_at_risk="173"/>
                <counts group_id="E2" subjects_affected="112" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="48" subjects_affected="38" subjects_at_risk="173"/>
                <counts group_id="E2" events="31" subjects_affected="25" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="26" subjects_affected="25" subjects_at_risk="173"/>
                <counts group_id="E2" events="27" subjects_affected="27" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="32" subjects_affected="30" subjects_at_risk="173"/>
                <counts group_id="E2" events="42" subjects_affected="40" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="28" subjects_affected="25" subjects_at_risk="173"/>
                <counts group_id="E2" events="20" subjects_affected="19" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="16" subjects_affected="14" subjects_at_risk="173"/>
                <counts group_id="E2" events="12" subjects_affected="11" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="21" subjects_affected="16" subjects_at_risk="173"/>
                <counts group_id="E2" events="13" subjects_affected="11" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="25" subjects_affected="22" subjects_at_risk="173"/>
                <counts group_id="E2" events="23" subjects_affected="21" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="173"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="173"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="25" subjects_affected="23" subjects_at_risk="173"/>
                <counts group_id="E2" events="21" subjects_affected="18" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="173"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="173"/>
                <counts group_id="E2" events="10" subjects_affected="9" subjects_at_risk="173"/>
              </event>
              <event>
                <sub_title>Hyperphosphataemia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="173"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="14" subjects_affected="13" subjects_at_risk="173"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="173"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Angela Capriati, Corporate Clinical Research Director</name_or_title>
      <organization>Menarini Ricerche S.p.A.</organization>
      <phone>+39 055 5680 ext 9933</phone>
      <email>acapriati@menarini-ricerche.it</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01724528
org study id: FLO-01
secondary id: 2012-000776-42
nct id: NCT01724528
lead sponsor: 
has dmc: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Serum Uric Acid (sUA) Level Control
time frame: 8 days
description: Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8)
measure: Preservation of Renal Function
time frame: 8 days
description: Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8)
measure: Treatment Responder Rate
time frame: 6 days
description: 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
measure: Assessment of Laboratory Tumor Lysis Syndrome (LTLS)
time frame: 6 days
description: 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.
measure: Assessment of Clinical Tumor Lysis Syndrome (CTLS)
time frame: 6 days
description: 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
measure: Treatment Emergent Signs or Symptoms (TESS)
time frame: 14 ± 2 days
description: Incidence, severity, seriousness and treatment-causality of TESS
arm group label: Febuxostat
arm group type: Experimental
description: Febuxostat for 7-9 days
arm group label: Allopurinol
arm group type: Active Comparator
description: Allopurinol for 7-9 days
intervention type: Drug
intervention name: Febuxostat
description: Standard dose PO (per os) from Day 1 to Day 7 (can be continued up to DAY 9 at investigator's discretion)
arm group label: Febuxostat
other name: Adenuric
intervention type: Drug
intervention name: Allopurinol
description: 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)
arm group label: Allopurinol
other name: Zyloric
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michele Spina, MD
role: Principal Investigator
affiliation: Centro Riferimento Oncologico (CRO) National Cancer Institute-Aviano-Italy
last name: Angela Capriati, MD, PhD
role: Study Director
affiliation: Menarini Ricerche S.p.A. - Florence-Italy
country: Italy
responsible party type: Sponsor
mesh term: Hematologic Neoplasms
mesh term: Tumor Lysis Syndrome
mesh term: Syndrome
mesh term: Allopurinol
mesh term: Febuxostat
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 