<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/NCT01713400</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-16743</org_study_id>
    <nct_id>NCT01713400</nct_id>
  </id_info>
  <brief_title>Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease</brief_title>
  <acronym>Ustekinumab</acronym>
  <official_title>Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>H. Lee Moffitt Cancer Center and Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gateway for Cancer Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>H. Lee Moffitt Cancer Center and Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine whether treatment with ustekinumab will alter the ratio of T Regulatory Cell&#xD;
      (Treg)/total cluster of differentiation 4 (CD4)+ cells in peripheral blood at day 30&#xD;
      post-hematopoietic cell transplantation (HCT).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a comparative study to assess the biologic and clinical activity of the agent&#xD;
      ustekinumab when given in concert with our established regimen of SIR/TAC. Patients will be&#xD;
      randomly assigned between the standard regimen of tacrolimus/sirolimus (TAC/SIR + placebo)&#xD;
      vs. the investigational regimen of tacrolimus/sirolimus/ustekinumab (TAC/SIR/U) in a 1:1&#xD;
      scheme.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 25, 2013</start_date>
  <completion_date type="Actual">June 14, 2018</completion_date>
  <primary_completion_date type="Actual">October 27, 2014</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio</measure>
    <time_frame>30 days post transplant</time_frame>
    <description>Median Blood Treg/Total CD4+ Ratio at day 30 following hematopoietic cell transplantation (HCT). Comparison between study arms: Ustekinumab vs. Placebo. From NCI Dictionary: &quot;T reg&quot; - A type of immune cell that blocks the actions of some other types of lymphocytes, to keep the immune system from becoming over-active. T regs are being studied in the treatment of cancer. A T reg is a type of white blood cell and a type of lymphocyte. Also called regulatory T cell, suppressor T cell, and T-regulatory cell.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Acute Graft vs. Host Disease (AGVHD)</measure>
    <time_frame>100 days post transplant</time_frame>
    <description>Cumulative incidence of Grade II - IV AGVHD to be characterized weekly from day of transplant to day 100 using the 1995 updated grading scheme for Graft vs. Host Disease (GVHD) developed by Glucksberg, et al.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Graft vs. Host Disease</condition>
  <arm_group>
    <arm_group_label>Ustekinumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ustekinumab</intervention_name>
    <description>One subcutaneous injection administered on day -1 and repeated on day +20 after transplant</description>
    <arm_group_label>Ustekinumab</arm_group_label>
    <other_name>STELARA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subcutaneous injection of sterile saline (identical volume to that of ustekinumab) administered via the identical route and schedule as ustekinumab.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>saline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus (TAC)</intervention_name>
    <description>Administered starting day -3 according to Blood and Marrow Transplant (BMT) Program standard operating procedures. TAC levels to be monitored and maintained at a target range of 3-7 given concurrent administration with sirolimus. Specific dose adjustments within this therapeutic range to be determined by the treating physician.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Ustekinumab</arm_group_label>
    <other_name>TAC</other_name>
    <other_name>Protopic</other_name>
    <other_name>Prograf</other_name>
    <other_name>Hecoria</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sirolimus</intervention_name>
    <description>Administered initially as an oral loading dose on day -1. Thereafter, SIR to be administered as an oral regimen daily. The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program. SIR levels to be monitored according to standard procedures. Dose adjustments to be made according to drug levels, with target range of 5-14ng/mL (therapeutic range by Abbott Architect instrument at Moffitt).</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Ustekinumab</arm_group_label>
    <other_name>SIR</other_name>
    <other_name>Rapamune</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Hematologic disorder requiring allogeneic hematopoietic cell transplantation&#xD;
&#xD;
          -  Adequate vital organ function:&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) &gt;/= 45% by multigated acquisition (MUGA)&#xD;
             scan&#xD;
&#xD;
          -  FEV1, FVC, and diffusing lung capacity oxygenation (DLCO) &gt;/= 50% of predicted values&#xD;
             on pulmonary function tests&#xD;
&#xD;
          -  Transaminases (AST, ALT) &lt; 3 times upper limit of normal values&#xD;
&#xD;
          -  Creatinine clearance &gt;/= 50 cc/min.&#xD;
&#xD;
          -  Performance status: Karnofsky Performance Status Score &gt;/= 60%.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active infection not controlled with appropriate antimicrobial therapy&#xD;
&#xD;
          -  HIV, hepatitis B, or hepatitis C infection&#xD;
&#xD;
          -  Sorror's co-morbidity factors with total score &gt; 3&#xD;
&#xD;
          -  Important modification to co-morbidity index calculation: DLCO will not be included in&#xD;
             assessment of pulmonary risk, excepting those with DLCO &lt; 50%, who will merit a score&#xD;
             of 3 and thereby be excluded from the trial.&#xD;
&#xD;
          -  Anti-thymocyte globulin (ATG) as part of the conditioning regimen&#xD;
&#xD;
          -  Cyclophosphamide as part of the conditioning regimens&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joseph Pidala, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>H. Lee Moffitt Cancer Center and Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center &amp; Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.moffitt.org/</url>
    <description>H. Lee Moffitt Cancer Center &amp; Research Institute</description>
  </link>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 24, 2012</study_first_posted>
  <results_first_submitted>July 15, 2015</results_first_submitted>
  <results_first_submitted_qc>August 10, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 10, 2015</results_first_posted>
  <last_update_submitted>March 2, 2020</last_update_submitted>
  <last_update_submitted_qc>March 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute Graft vs. Host Disease (aGVHD)</keyword>
  <keyword>Graft vs. Host Disease (GVHD)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Ustekinumab</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>54 participants (potential donors and recipients) were enrolled at Moffitt Cancer Center from 3/15/2013 through 5/22/2014.</recruitment_details>
      <pre_assignment_details>30 eligible recipients were randomly assigned 1:1 (Ustekinumab n=15, Placebo n=15) with stratification for donor type. Results Data pertains to recipients only.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ustekinumab</title>
          <description>Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participating recipients</population>
      <group_list>
        <group group_id="B1">
          <title>Ustekinumab</title>
          <description>Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</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="15"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="30"/>
          </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </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="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="19"/>
                  </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="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio</title>
        <description>Median Blood Treg/Total CD4+ Ratio at day 30 following hematopoietic cell transplantation (HCT). Comparison between study arms: Ustekinumab vs. Placebo. From NCI Dictionary: &quot;T reg&quot; - A type of immune cell that blocks the actions of some other types of lymphocytes, to keep the immune system from becoming over-active. T regs are being studied in the treatment of cancer. A T reg is a type of white blood cell and a type of lymphocyte. Also called regulatory T cell, suppressor T cell, and T-regulatory cell.</description>
        <time_frame>30 days post transplant</time_frame>
        <population>All participating recipients</population>
        <group_list>
          <group group_id="O1">
            <title>Ustekinumab</title>
            <description>Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
          </group>
        </group_list>
        <measure>
          <title>T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio</title>
          <description>Median Blood Treg/Total CD4+ Ratio at day 30 following hematopoietic cell transplantation (HCT). Comparison between study arms: Ustekinumab vs. Placebo. From NCI Dictionary: &quot;T reg&quot; - A type of immune cell that blocks the actions of some other types of lymphocytes, to keep the immune system from becoming over-active. T regs are being studied in the treatment of cancer. A T reg is a type of white blood cell and a type of lymphocyte. Also called regulatory T cell, suppressor T cell, and T-regulatory cell.</description>
          <population>All participating recipients</population>
          <units>ratio</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13" lower_limit="2" upper_limit="22"/>
                    <measurement group_id="O2" value="11" lower_limit="3" upper_limit="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Acute Graft vs. Host Disease (AGVHD)</title>
        <description>Cumulative incidence of Grade II - IV AGVHD to be characterized weekly from day of transplant to day 100 using the 1995 updated grading scheme for Graft vs. Host Disease (GVHD) developed by Glucksberg, et al.</description>
        <time_frame>100 days post transplant</time_frame>
        <population>All participating recipients</population>
        <group_list>
          <group group_id="O1">
            <title>Ustekinumab</title>
            <description>Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Acute Graft vs. Host Disease (AGVHD)</title>
          <description>Cumulative incidence of Grade II - IV AGVHD to be characterized weekly from day of transplant to day 100 using the 1995 updated grading scheme for Graft vs. Host Disease (GVHD) developed by Glucksberg, et al.</description>
          <population>All participating recipients</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3"/>
                    <measurement group_id="O2" value="40.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year, 6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Ustekinumab</title>
          <description>Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>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="4" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other, TMA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other, Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastric hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Acute cholecystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, GVHD of gut</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatobiliary disorders - Other, VOD</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Portal hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bladder infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, HHV6 infection affecting CNS</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hallucinations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, elevated creatinine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, renal failure-dialysis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, GVHD of skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <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="8" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood and lymphatic disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="7" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="8" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatobiliary disorders - Other</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Rhinitis infective</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="5" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>GGT increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchopulmonary hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Laryngeal mucositis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </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>Dr. Joseph Pidala</name_or_title>
      <organization>H. Lee Moffitt Cancer Center and Research Institute</organization>
      <phone>813-745-2556</phone>
      <email>joseph.pidala@moffitt.org</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/NCT01713400
org study id: MCC-16743
nct id: NCT01713400
lead sponsor: 
collaborator: 
has dmc: Yes
To determine whether treatment with ustekinumab will alter the ratio of T Regulatory Cell
      (Treg)/total cluster of differentiation 4 (CD4)+ cells in peripheral blood at day 30
      post-hematopoietic cell transplantation (HCT).
This is a comparative study to assess the biologic and clinical activity of the agent
      ustekinumab when given in concert with our established regimen of SIR/TAC. Patients will be
      randomly assigned between the standard regimen of tacrolimus/sirolimus (TAC/SIR + placebo)
      vs. the investigational regimen of tacrolimus/sirolimus/ustekinumab (TAC/SIR/U) in a 1:1
      scheme.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio
time frame: 30 days post transplant
description: Median Blood Treg/Total CD4+ Ratio at day 30 following hematopoietic cell transplantation (HCT). Comparison between study arms: Ustekinumab vs. Placebo. From NCI Dictionary: "T reg" - A type of immune cell that blocks the actions of some other types of lymphocytes, to keep the immune system from becoming over-active. T regs are being studied in the treatment of cancer. A T reg is a type of white blood cell and a type of lymphocyte. Also called regulatory T cell, suppressor T cell, and T-regulatory cell.
measure: Incidence of Acute Graft vs. Host Disease (AGVHD)
time frame: 100 days post transplant
description: Cumulative incidence of Grade II - IV AGVHD to be characterized weekly from day of transplant to day 100 using the 1995 updated grading scheme for Graft vs. Host Disease (GVHD) developed by Glucksberg, et al.
arm group label: Ustekinumab
arm group type: Experimental
description: Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.
intervention type: Drug
intervention name: Ustekinumab
description: One subcutaneous injection administered on day -1 and repeated on day +20 after transplant
arm group label: Ustekinumab
other name: STELARA
intervention type: Drug
intervention name: Placebo
description: Subcutaneous injection of sterile saline (identical volume to that of ustekinumab) administered via the identical route and schedule as ustekinumab.
arm group label: Placebo
other name: saline
intervention type: Drug
intervention name: Tacrolimus (TAC)
description: Administered starting day -3 according to Blood and Marrow Transplant (BMT) Program standard operating procedures. TAC levels to be monitored and maintained at a target range of 3-7 given concurrent administration with sirolimus. Specific dose adjustments within this therapeutic range to be determined by the treating physician.
arm group label: Placebo
arm group label: Ustekinumab
other name: TAC
other name: Protopic
other name: Prograf
other name: Hecoria
intervention type: Drug
intervention name: Sirolimus
description: Administered initially as an oral loading dose on day -1. Thereafter, SIR to be administered as an oral regimen daily. The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program. SIR levels to be monitored according to standard procedures. Dose adjustments to be made according to drug levels, with target range of 5-14ng/mL (therapeutic range by Abbott Architect instrument at Moffitt).
arm group label: Placebo
arm group label: Ustekinumab
other name: SIR
other name: Rapamune
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Joseph Pidala, MD, MS
role: Principal Investigator
affiliation: H. Lee Moffitt Cancer Center and Research Institute
facility: 
country: United States
url: http://www.moffitt.org/
description: H. Lee Moffitt Cancer Center & Research Institute
responsible party type: Sponsor
mesh term: Graft vs Host Disease
mesh term: Sirolimus
mesh term: Ustekinumab
mesh term: Tacrolimus
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 