<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/NCT01686165</url>
  </required_header>
  <id_info>
    <org_study_id>12-0288-04</org_study_id>
    <secondary_id>NCI-2012-01131</secondary_id>
    <secondary_id>1200000288</secondary_id>
    <secondary_id>P30CA023074</secondary_id>
    <nct_id>NCT01686165</nct_id>
  </id_info>
  <brief_title>Belinostat and Yttrium Y 90 Ibritumomab Tiuxetan in Patients W/Relapsed Aggressive B-Cell NHL</brief_title>
  <official_title>A Phase II Exploratory Study of PXD-101(Belinostat) Followed by Zevalin in Patients With Relapsed Aggressive High-Risk Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Arizona</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Arizona</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study looks at what effects (good and bad) a drug called PXD-101 (belinostat) in&#xD;
      combination with the radioactive drug Zevalin (yttrium Y 90 ibritumomab tiuxetan) has on&#xD;
      patients with relapsed aggressive (high-risk) non-Hodgkin lymphoma. Studies in the laboratory&#xD;
      suggest that drugs such as PXD101 can act upon specific cancer cell processes to cause either&#xD;
      death of the cancer cells or prevention of their growth. In human studies with a small number&#xD;
      of patients with this lymphoma, PXD-101 has shown the ability to shrink and slow tumor&#xD;
      growth. When Zevalin is delivered directly to the tumor, the lymphoma cells are destroyed and&#xD;
      this may result in the disappearance of the tumor (remission)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To document the complete response rate and overall response for patients with relapsed&#xD;
      aggressive high-risk non-Hodgkin's lymphoma treated with two cycles PXD-101 followed by one&#xD;
      cycle of Zevalin.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate 2-year progression-free survival in patients with relapsed aggressive&#xD;
      high-risk non-Hodgkin's lymphoma treated with two cycles PXD-101 followed by one cycle of&#xD;
      Zevalin.&#xD;
&#xD;
      II. To evaluate the toxicity of two cycles PXD-101 and one cycle of Zevalin in patients with&#xD;
      relapsed aggressive high-risk non-Hodgkin's lymphoma.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive belinostat intravenously (IV) over 30-60 minutes on days 1-5. Treatment with&#xD;
      belinostat repeats every 21 days for 2 courses. Patients then receive rituximab IV on days 1&#xD;
      and either 7, 8, or 9, and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 50.&#xD;
      Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 2 years and&#xD;
      then every 6 months for 3 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 31, 2012</start_date>
  <completion_date type="Actual">November 9, 2017</completion_date>
  <primary_completion_date type="Actual">February 9, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete Response Rate</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>To document the complete response rate for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma (NHL) treated with two cycles PXD-101 followed by one cycle of the Zevalin regimen.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Response</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>To document the overall response for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma (NHL) treated with two cycles PXD-101 followed by one cycle of the Zevalin regimen.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>2 years</time_frame>
    <description>Will be estimated using a Kaplan-Meier estimate. The observed 2-year progression-free survival rate will be estimated (with a 95% confidence interval) from the Kaplan-Meier curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Adverse Events and Serious Adverse Events</measure>
    <time_frame>Up to 30 days after patient receives last dose of study drug</time_frame>
    <description>The proportion of patients with a given adverse event will be tabulated and the 95% confidence interval computed.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Anaplastic Large Cell Lymphoma</condition>
  <condition>Recurrent Adult Diffuse Large Cell Lymphoma</condition>
  <condition>Recurrent Mantle Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Belinostat Yttrium Ibritumomab Tiuxetan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive belinostat IV over 30-60 minutes on days 1-5. Treatment with belinostat repeats every 21 days for 2 courses. Patients then receive rituximab IV on days 1 and either 7, 8, or 9, and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 50. Treatment continues in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>belinostat</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Belinostat Yttrium Ibritumomab Tiuxetan</arm_group_label>
    <other_name>PXD101</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>rituximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Belinostat Yttrium Ibritumomab Tiuxetan</arm_group_label>
    <other_name>IDEC-C2B8</other_name>
    <other_name>IDEC-C2B8 monoclonal antibody</other_name>
    <other_name>Mabthera</other_name>
    <other_name>MOAB IDEC-C2B8</other_name>
    <other_name>Rituxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>yttrium Y 90 ibritumomab tiuxetan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Belinostat Yttrium Ibritumomab Tiuxetan</arm_group_label>
    <other_name>90Y ibritumomab tiuxetan</other_name>
    <other_name>IDEC Y2B8</other_name>
    <other_name>Y90 Zevalin</other_name>
    <other_name>Y90-labeled ibritumomab tiuxetan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biopsy confirmed, CD20 positive diffuse large B-cell lymphoma, primary mediastinal&#xD;
             b-cell lymphoma, mantel cell lymphoma, transformed indolent lymphoma, high&#xD;
             grade-B-cell lymphoma; AND bone marrow must show =&lt; 20% CD20+ B-cells with &gt;= 15%&#xD;
             cellularity within 42 days of study registration&#xD;
&#xD;
          -  Any stage disease&#xD;
&#xD;
          -  Patients must have been previously treated:&#xD;
&#xD;
               -  &gt;= 3rd line if bone marrow transplant (BMT) candidate OR&#xD;
&#xD;
               -  &gt;= 2nd line if not BMT candidate OR&#xD;
&#xD;
               -  &gt;= 2nd relapse for BMT candidate OR&#xD;
&#xD;
               -  &gt;= 1st relapse for non- BMT candidate&#xD;
&#xD;
          -  Must have a diagnostic quality CT scan of the chest, abdomen and pelvis OR baseline&#xD;
             PET-CT scan performed within 28 days prior to registration&#xD;
&#xD;
          -  Must have bidimensionally measurable disease with lesions at least 1.5 cm in one&#xD;
             dimension ALL measurable disease must be assessed within 28 days of registration&#xD;
&#xD;
          -  To determine prior drug regimens: radiation therapy counts as 1 treatment, BMT&#xD;
             including induction counts as one treatment, radioimmunotherapy is not considered a&#xD;
             chemotherapy regimen, rituximab alone is not considered a treatment; all prior therapy&#xD;
             must have been completed at least 30 days prior to registration; patients should not&#xD;
             have taken valproic acid, or any other histone deacetylase inhibitor (eg., vorinostat,&#xD;
             romidepsin), for at least 30 days prior to registration; patients must have recovered&#xD;
             from any toxicities related to therapies prior to registration&#xD;
&#xD;
          -  No clinical evidence of CNS involvement by lymphoma, any lab (eg., LDH or radiographic&#xD;
             tests performed to access CNS involvement must be negative and must be performed&#xD;
             within 42 days prior to registration&#xD;
&#xD;
          -  Unilateral or bilateral bone marrow biopsy performed within 42 days prior to&#xD;
             registration&#xD;
&#xD;
          -  Life expectancy of greater than 3 months&#xD;
&#xD;
          -  Karnofsky performance status &gt;= 60%&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  AST (SGOT)/ALT(SGPT) =&lt; 2.5 X institutional upper limit of normal&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 X institutional upper limit of normal (unless associated with&#xD;
             Gilbert's syndrome)&#xD;
&#xD;
          -  Serum creatinine &lt; 2 x institutional upper limit of normal OR&#xD;
&#xD;
          -  Measured creatinine clearance &gt;= 60 mL/min&#xD;
&#xD;
          -  LDH &lt; 1.50 X institutional upper limit of normal&#xD;
&#xD;
          -  EKG with no significant abnormalities within 28 days prior to registration&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had chemotherapy or radiotherapy within 30 days (6 weeks for&#xD;
             nitrosoureas or mitomycin C) prior to study screening or those who have not recovered&#xD;
             from adverse events due to agents administered more than 4 weeks earlier&#xD;
&#xD;
          -  Prior radioimmunotherapy&#xD;
&#xD;
          -  Pregnant or nursing&#xD;
&#xD;
          -  Clinical evidence of CNS involvement by lymphoma&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to PXD-101 or Zevalin or other agents used in the study&#xD;
&#xD;
          -  Concomitant medication that may cause Torsade de Pointes, i.e. prolongation of the QT&#xD;
             interval &gt; 500 msec&#xD;
&#xD;
          -  Significant cardiovascular disease including unstable angina pectoris, uncontrolled&#xD;
             hypertension, congestive heart failure related to primary cardiac disease, any&#xD;
             condition requiring anti-arrhythmic therapy, ischemic or valvular heart disease, or a&#xD;
             myocardial infarction within the past 6 months&#xD;
&#xD;
          -  Current long QT syndrome or baseline prolongation of QT/QTcF interval, i.e.&#xD;
             demonstration of a QTcF interval &gt; 450 msec&#xD;
&#xD;
          -  Clinical evidence of severe peripheral vascular disease, diabetic ulcers or venous&#xD;
             stasis ulcers, or history of deep venous or arterial thrombosis within 3 months prior&#xD;
             to screening&#xD;
&#xD;
          -  Known to be human immunodeficiency virus (HIV) positive or with known acquired&#xD;
             immunodeficiency syndrome (AIDS) syndrome&#xD;
&#xD;
          -  Patients may not be receiving any other investigational agents&#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>Daniel O. Persky, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Arizona</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Arizona Cancer Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724-5024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2012</study_first_posted>
  <results_first_submitted>July 2, 2018</results_first_submitted>
  <results_first_submitted_qc>July 2, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">July 31, 2018</results_first_posted>
  <last_update_submitted>July 30, 2018</last_update_submitted>
  <last_update_submitted_qc>July 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Lymphoma, Large-Cell, Anaplastic</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Belinostat</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>PXD-101 (d1-d5) for 2 Cycles &gt; Zevalin 1 Cycle</title>
          <description>Treatment with PXD101 will be administered intravenously** at a dose of 1,000 mg/m2 IV days 1-5 every 21 days for 2 cycles. Yttrium-90 ibritumomab tiuxetan (Zevalin®) Administration. Y-90 Zevalin will be administered to all subjects in accordance with the approved Zevalin product labeling. Treatment will be administered on an outpatient basis.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>PXD-101 (d1-d5) for 2 Cycles &gt; Zevalin 1 Cycle</title>
          <description>Treatment with PXD101 will be administered intravenously** at a dose of 1,000 mg/m2 IV days 1-5 every 21 days for 2 cycles. Yttrium-90 ibritumomab tiuxetan (Zevalin®) Administration. Y-90 Zevalin will be administered to all subjects in accordance with the approved Zevalin product labeling. Treatment will be administered on an outpatient basis.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Complete Response Rate</title>
        <description>To document the complete response rate for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma (NHL) treated with two cycles PXD-101 followed by one cycle of the Zevalin regimen.</description>
        <time_frame>Up to 5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>PXD-101 (d1-d5) for 2 Cycles &gt; Zevalin 1 Cycle</title>
            <description>Treatment with PXD101 will be administered intravenously** at a dose of 1,000 mg/m2 IV days 1-5 every 21 days for 2 cycles. Yttrium-90 ibritumomab tiuxetan (Zevalin®) Administration. Y-90 Zevalin will be administered to all subjects in accordance with the approved Zevalin product labeling. Treatment will be administered on an outpatient basis.</description>
          </group>
        </group_list>
        <measure>
          <title>Complete Response Rate</title>
          <description>To document the complete response rate for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma (NHL) treated with two cycles PXD-101 followed by one cycle of the Zevalin regimen.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Response</title>
        <description>To document the overall response for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma (NHL) treated with two cycles PXD-101 followed by one cycle of the Zevalin regimen.</description>
        <time_frame>Up to 5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>PXD-101 (d1-d5) for 2 Cycles &gt; Zevalin 1 Cycle</title>
            <description>Treatment with PXD101 will be administered intravenously** at a dose of 1,000 mg/m2 IV days 1-5 every 21 days for 2 cycles. Yttrium-90 ibritumomab tiuxetan (Zevalin®) Administration. Y-90 Zevalin will be administered to all subjects in accordance with the approved Zevalin product labeling. Treatment will be administered on an outpatient basis.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response</title>
          <description>To document the overall response for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma (NHL) treated with two cycles PXD-101 followed by one cycle of the Zevalin regimen.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival</title>
        <description>Will be estimated using a Kaplan-Meier estimate. The observed 2-year progression-free survival rate will be estimated (with a 95% confidence interval) from the Kaplan-Meier curve.</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>PXD-101 (d1-d5) for 2 Cycles &gt; Zevalin 1 Cycle</title>
            <description>Treatment with PXD101 will be administered intravenously** at a dose of 1,000 mg/m2 IV days 1-5 every 21 days for 2 cycles. Yttrium-90 ibritumomab tiuxetan (Zevalin®) Administration. Y-90 Zevalin will be administered to all subjects in accordance with the approved Zevalin product labeling. Treatment will be administered on an outpatient basis.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>Will be estimated using a Kaplan-Meier estimate. The observed 2-year progression-free survival rate will be estimated (with a 95% confidence interval) from the Kaplan-Meier curve.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Adverse Events and Serious Adverse Events</title>
        <description>The proportion of patients with a given adverse event will be tabulated and the 95% confidence interval computed.</description>
        <time_frame>Up to 30 days after patient receives last dose of study drug</time_frame>
        <group_list>
          <group group_id="O1">
            <title>PXD-101 (d1-d5) for 2 Cycles &gt; Zevalin 1 Cycle</title>
            <description>Treatment with PXD101 will be administered intravenously** at a dose of 1,000 mg/m2 IV days 1-5 every 21 days for 2 cycles. Yttrium-90 ibritumomab tiuxetan (Zevalin®) Administration. Y-90 Zevalin will be administered to all subjects in accordance with the approved Zevalin product labeling. Treatment will be administered on an outpatient basis.</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Adverse Events and Serious Adverse Events</title>
          <description>The proportion of patients with a given adverse event will be tabulated and the 95% confidence interval computed.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Three years, six months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>PXD-101 (d1-d5) for 2 Cycles &gt; Zevalin 1 Cycle</title>
          <description>Treatment with PXD101 will be administered intravenously** at a dose of 1,000 mg/m2 IV days 1-5 every 21 days for 2 cycles. Yttrium-90 ibritumomab tiuxetan (Zevalin®) Administration. Y-90 Zevalin will be administered to all subjects in accordance with the approved Zevalin product labeling. Treatment will be administered on an outpatient basis.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Deep Venous Thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Increased Serum Creatinine</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Otitis Media</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea/Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Transaminitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Sensory Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Edema - lower extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Daniel Persky, M.D.</name_or_title>
      <organization>University of Arizona Cancer Center</organization>
      <phone>520-626-8908</phone>
      <email>dpersky@uacc.arizona.edu</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/NCT01686165
org study id: 12-0288-04
secondary id: NCI-2012-01131
secondary id: 1200000288
secondary id: P30CA023074
nct id: NCT01686165
lead sponsor: 
collaborator: 
has dmc: Yes
This study looks at what effects (good and bad) a drug called PXD-101 (belinostat) in
      combination with the radioactive drug Zevalin (yttrium Y 90 ibritumomab tiuxetan) has on
      patients with relapsed aggressive (high-risk) non-Hodgkin lymphoma. Studies in the laboratory
      suggest that drugs such as PXD101 can act upon specific cancer cell processes to cause either
      death of the cancer cells or prevention of their growth. In human studies with a small number
      of patients with this lymphoma, PXD-101 has shown the ability to shrink and slow tumor
      growth. When Zevalin is delivered directly to the tumor, the lymphoma cells are destroyed and
      this may result in the disappearance of the tumor (remission)
PRIMARY OBJECTIVES:

      I. To document the complete response rate and overall response for patients with relapsed
      aggressive high-risk non-Hodgkin's lymphoma treated with two cycles PXD-101 followed by one
      cycle of Zevalin.

      SECONDARY OBJECTIVES:

      I. To estimate 2-year progression-free survival in patients with relapsed aggressive
      high-risk non-Hodgkin's lymphoma treated with two cycles PXD-101 followed by one cycle of
      Zevalin.

      II. To evaluate the toxicity of two cycles PXD-101 and one cycle of Zevalin in patients with
      relapsed aggressive high-risk non-Hodgkin's lymphoma.

      OUTLINE:

      Patients receive belinostat intravenously (IV) over 30-60 minutes on days 1-5. Treatment with
      belinostat repeats every 21 days for 2 courses. Patients then receive rituximab IV on days 1
      and either 7, 8, or 9, and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 50.
      Treatment continues in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years and
      then every 6 months for 3 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete Response Rate
time frame: Up to 5 years
description: To document the complete response rate for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma (NHL) treated with two cycles PXD-101 followed by one cycle of the Zevalin regimen.
measure: Overall Response
time frame: Up to 5 years
description: To document the overall response for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma (NHL) treated with two cycles PXD-101 followed by one cycle of the Zevalin regimen.
measure: Progression-free Survival
time frame: 2 years
description: Will be estimated using a Kaplan-Meier estimate. The observed 2-year progression-free survival rate will be estimated (with a 95% confidence interval) from the Kaplan-Meier curve.
measure: Occurrence of Adverse Events and Serious Adverse Events
time frame: Up to 30 days after patient receives last dose of study drug
description: The proportion of patients with a given adverse event will be tabulated and the 95% confidence interval computed.
arm group label: Belinostat Yttrium Ibritumomab Tiuxetan
arm group type: Experimental
description: Patients receive belinostat IV over 30-60 minutes on days 1-5. Treatment with belinostat repeats every 21 days for 2 courses. Patients then receive rituximab IV on days 1 and either 7, 8, or 9, and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 50. Treatment continues in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: belinostat
description: Given IV
arm group label: Belinostat Yttrium Ibritumomab Tiuxetan
other name: PXD101
intervention type: Biological
intervention name: rituximab
description: Given IV
arm group label: Belinostat Yttrium Ibritumomab Tiuxetan
other name: IDEC-C2B8
other name: IDEC-C2B8 monoclonal antibody
other name: Mabthera
other name: MOAB IDEC-C2B8
other name: Rituxan
intervention type: Radiation
intervention name: yttrium Y 90 ibritumomab tiuxetan
description: Given IV
arm group label: Belinostat Yttrium Ibritumomab Tiuxetan
other name: 90Y ibritumomab tiuxetan
other name: IDEC Y2B8
other name: Y90 Zevalin
other name: Y90-labeled ibritumomab tiuxetan
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel O. Persky, MD
role: Principal Investigator
affiliation: University of Arizona
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Lymphoma, Large-Cell, Anaplastic
mesh term: Recurrence
mesh term: Rituximab
mesh term: Belinostat
mesh term: Antibodies, Monoclonal
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 