<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/NCT02254551</url>
  </required_header>
  <id_info>
    <org_study_id>SCRI MM 50</org_study_id>
    <nct_id>NCT02254551</nct_id>
  </id_info>
  <brief_title>Safety/Efficacy Study of LDE225 (Sonidegib) Plus Bortezomib in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma</brief_title>
  <official_title>Phase II Trial of LDE225 (Sonidegib) Plus Bortezomib in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma With a Dose-Finding Lead-In</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SCRI Development Innovations, LLC</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>SCRI Development Innovations, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine whether the combination of LDE225 (sonidegib) plus&#xD;
      bortezomib is safe and effective in the treatment of relapsed or relapsed/refractory multiple&#xD;
      myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Although multiple myeloma (MM) is considered fatal, survival has dramatically improved with&#xD;
      the introduction of more effective treatment options. Despite these advances, all patients&#xD;
      eventually relapse and MM is generally considered incurable. LDE225 (Sonidegib) is an oral,&#xD;
      investigational smoothened (SMO) inhibitor that has shown anti-tumor activity in certain&#xD;
      cancers. Bortezomib is a highly active drug for the treatment of MM and has produced response&#xD;
      rates in relapsed and/or refractory patients. This study will investigate the tolerability&#xD;
      and feasibility of combining LDE225 with bortezomib in patients with bortezomib-sensitive&#xD;
      relapsed or relapsed/refractory MM.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Safety lead-in data did not support continuation of study.&#xD;
  </why_stopped>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</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>Maximum Tolerated Dose (MTD) of LDE225 Plus Bortezomib</measure>
    <time_frame>every 3 weeks up to 48 weeks</time_frame>
    <description>During the safety lead-in, a standard 3+3 dose escalation design was used to establish the MTD for LDE225 in combination with bortezomib. The MTD would be determined by the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during one cycle (21 days) of therapy. If 2 of 6 patients within a dose level experienced a DLT, that dose level would be defined as exceeding MTD and no further dose escalation would occur. The previous dose level would be considered the MTD.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Disease Progression</measure>
    <time_frame>every 3 weeks up to 48 weeks, then every 3 months thereafter up to 3 years from initiation of study treatment.</time_frame>
    <description>Time to progression (TTP) is measured from Day 1 of study drug administration to disease progression using International Myeloma Working Group (IMWG) Uniform Response Criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response</measure>
    <time_frame>Every 3 weeks up to 48 weeks</time_frame>
    <description>Number of patients with confirmed Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Progressive Disease (PD) or Stable Disease (SD) according to International Myeloma Working Group (IMWG) Uniform Response Criteria. CR=5% or less plasma cells in bone marrow, disappearance of soft tissue plasmacytoma, negative immunofixation on serum and urine. VGPR=Serum and urine M-protein detectable by immunofixation but not by electrophoresis, disappearance of any soft tissue plasmacytomas that were present at baseline. PR= at least 50% reduction from baseline in serum M-protein and at least 90% reduction from baseline in 24hr urinary M-protein. PD=Increase of 25% or more from nadir in serum or urine proteins. SD= not meeting criteria for CR, VGPR, PR or PD.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>LDE225 Plus Bortezomib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lead-In Portion: The lead-in portion of this study will investigate the safety and tolerability, and determine the MTD of LDE225, in combination with bortezomib in this patient population.&#xD;
Expansion Portion: Eligible patients will receive LDE225 orally once daily for 21 days with the dose-level determined in the lead-in portion of the study. Eligible patients will also receive a standard regimen of bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LDE225</intervention_name>
    <description>Lead-In: LDE225 will be administered orally at three dose levels starting at 400mg. If acceptable tolerability is demonstrated, escalations may continue up to 800 mg. LDE225 will be administered orally as a single daily dose for 21 days in combination with a fixed dose of bortezomib to be given on Days 1, 4, 8, 11 of each 21 day cycle.&#xD;
Dose Expansion: LDE225 will be given as a single oral daily dose for 21 days at the MTD determined in the lead-in phase.&#xD;
Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity.</description>
    <arm_group_label>LDE225 Plus Bortezomib</arm_group_label>
    <other_name>Sonidegib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <description>In both the lead-in and dose expansion portions of the study, bortezomib, 1.3 mg/m2, will be administered by subcutaneous injection (SQ) on Days 1, 4, 8, 11 of each 21 day cycle.</description>
    <arm_group_label>LDE225 Plus Bortezomib</arm_group_label>
    <other_name>Velcade</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have measurable MM requiring systemic therapy defined as at least one of&#xD;
             the following:&#xD;
&#xD;
               -  Serum M-protein ≥ 0.5 g/dL&#xD;
&#xD;
               -  Urine M-protein ≥ 200 mg/24 hrs&#xD;
&#xD;
               -  Serum free light chain assay: involved free light chain level ≥ 10 mg/dL provided&#xD;
                  the serum free light chain ratio is abnormal&#xD;
&#xD;
          2. Must have progressed during or after at least two previous treatment regimens.&#xD;
             Patients who have received previous high dose therapy or autologous stem cell&#xD;
             transplantation are eligible.&#xD;
&#xD;
          3. ECOG Performance Status score of 0-2.&#xD;
&#xD;
          4. Patients with adequate bone marrow, liver and renal function.&#xD;
&#xD;
          5. Patient is able to swallow and retain oral medication.&#xD;
&#xD;
          6. QTcF ≤450 msec for males and ≤ 470 msec for females on the screening ECG.&#xD;
&#xD;
          7. Female patients must not be of childbearing potential or must agree to use adequate&#xD;
             contraceptive measures.&#xD;
&#xD;
          8. Male patients willing to use adequate contraceptive measures.&#xD;
&#xD;
          9. Willingness and ability to comply with study and follow-up procedures.&#xD;
&#xD;
         10. Ability to understand the nature of this study and give written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received any treatment for myeloma-directed treatment within 21 days. Localized&#xD;
             radiation and dexamethasone must be completed within 7 days prior to study treatment&#xD;
&#xD;
          2. Refractory to bortezomib, defined as progression on or within 60 days of last&#xD;
             bortezomib dose.&#xD;
&#xD;
          3. Received any investigational drug within 28 days or 5 half-lives (whichever is longer)&#xD;
             prior to the first dose of LDE225. For other anti-neoplastic therapy (e.g.,&#xD;
             chemotherapy, targeted therapy or radiation), a minimum of 14 days between termination&#xD;
             of the study drug and administration of LDE225 is required.&#xD;
&#xD;
          4. Patients who have previously been treated with systemic LDE225 or with other Hedgehog&#xD;
             (Hh) pathway inhibitors.&#xD;
&#xD;
          5. Received major surgical procedures within 28 days of beginning study drug, or minor&#xD;
             surgical procedures within 7 days. No waiting is required following port-a-cath&#xD;
             placement.&#xD;
&#xD;
          6. Those who are pregnant or lactating.&#xD;
&#xD;
          7. Patients with concurrent uncontrolled medical conditions that may interfere with their&#xD;
             participation in the study or potentially affect the interpretation of the study data.&#xD;
&#xD;
          8. Patients with &gt; Grade 2 peripheral neuropathy (per NCI CTCAE V4.0) within 14 days&#xD;
             prior to study enrollment.&#xD;
&#xD;
          9. Patients with a presence of active gastrointestinal disease or other condition that&#xD;
             will interfere significantly with the absorption, distribution, metabolism, or&#xD;
             excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting,&#xD;
             diarrhea Grade ≥2, and malabsorption syndrome).&#xD;
&#xD;
         10. Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular&#xD;
             dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on&#xD;
             concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as&#xD;
             HMG CoA inhibitors (statins), clofibrate and gemfibrozil, and that cannot be&#xD;
             discontinued at least 2 weeks prior to starting LDE225 treatment. If it is essential&#xD;
             that the patient stays on a statin to control hyperlipidemia, only pravastatin may be&#xD;
             used with extra caution.&#xD;
&#xD;
         11. Patients who are planning on embarking on a new strenuous exercise regimen after&#xD;
             initiation of study treatment. Muscular activities, such as strenuous exercise, that&#xD;
             can result in significant increases in plasma CK levels should be avoided while on&#xD;
             LDE225 treatment.&#xD;
&#xD;
         12. Receiving treatment with medications known to be moderate and strong inhibitors or&#xD;
             inducers of CYP3A4 or CYP3A5, drugs that are BCRP substrates, or drugs metabolized by&#xD;
             CYP2B6 or CYP2C9 that have narrow therapeutic index, and that cannot be discontinued&#xD;
             before starting treatment with LDE225. Medications that are strong CYP3A4 or CYP3A5&#xD;
             inhibitors should be discontinued at least 7 days prior to starting LDE225. Strong&#xD;
             CYP3A4 or CYP3A5 inducers should be discontinued at least 2 weeks weeks weeks prior to&#xD;
             starting treatment with LDE225.&#xD;
&#xD;
         13. Therapeutic doses of warfarin sodium or any other warfarin-derivative anticoagulants&#xD;
             are not permitted since LDE225 is a competitive inhibitor of CYP2C9 based on the in&#xD;
             vitro data. In this situation therapeutic anticoagulation may be accomplished using&#xD;
             low molecular weight heparin (LMWH) or similar agents.&#xD;
&#xD;
         14. Those diagnosed with cardiac conditions currently or within last 6 months.&#xD;
&#xD;
         15. Those experiencing angina pectoris within 3 months.&#xD;
&#xD;
         16. Those who experienced acute myocardial infarction within 3 months.&#xD;
&#xD;
         17. Those with inadequately controlled hypertension defined as systolic blood pressure&#xD;
             [SBP] &gt; 180 mmHg or diastolic blood pressure (DBP) &gt; 100 mmHg. Patients with values&#xD;
             above these levels must have their blood pressure controlled with medication prior to&#xD;
             starting treatment. Patients with a history of labile hypertension, or a history of&#xD;
             poor compliance with an antihypertensive regimen are to be excluded.&#xD;
&#xD;
         18. Pregnant or lactating women, where pregnancy is confirmed by a positive human&#xD;
             chorionic gonadotropin (hCG) laboratory test.&#xD;
&#xD;
         19. Patients who are not willing to apply highly effective contraception during the study&#xD;
             and after the final dose of study treatment.&#xD;
&#xD;
         20. Sexually active males who are unwilling to use a condom during intercourse while&#xD;
             taking drug and for 6 months after stopping investigational medications and agree not&#xD;
             to father a child in this period.&#xD;
&#xD;
         21. Those with a serious active infection at the time of treatment, or another serious&#xD;
             underlying medical condition that would impair the ability of the patient to receive&#xD;
             protocol treatment.&#xD;
&#xD;
         22. Those presenting with other active cancers, or history of treatment for invasive&#xD;
             cancer within 3 years. Patients with Stage I cancer who have received definitive local&#xD;
             treatment and are considered unlikely to recur are eligible. All patients with&#xD;
             previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are&#xD;
             patients with history of non-melanoma skin cancer.&#xD;
&#xD;
         23. Those with psychological, familial, sociological, or geographical conditions that do&#xD;
             not permit compliance with the protocol.&#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>Jesus G. Berdeja, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>SCRI Development Innovations, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Colorado Blood Cancer Institute</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology Care</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology PLLC</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Transplant Institute/Methodist Healthcare</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <results_first_submitted>October 28, 2016</results_first_submitted>
  <results_first_submitted_qc>December 23, 2016</results_first_submitted_qc>
  <results_first_posted type="Actual">February 16, 2017</results_first_posted>
  <last_update_submitted>December 23, 2016</last_update_submitted>
  <last_update_submitted_qc>December 23, 2016</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>relapsed multiple myeloma</keyword>
  <keyword>refractory multiple myeloma</keyword>
  <keyword>LDE225</keyword>
  <keyword>Sonidegib</keyword>
  <keyword>bortezomib</keyword>
  <keyword>smoothened (SMO) inhibitors</keyword>
  <keyword>Velcade</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bortezomib</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The primary objective of this study was to investigate safety, tolerability and determine the maximum tolerated dose (MTD) of LDE225 to administer along with a fixed dose of bortezomib. Between March 2015 and September 2015, 7 patients were enrolled in the safety lead-in part of the study at 4 investigational sites in the U.S.</recruitment_details>
      <pre_assignment_details>7 patients received at least 1 cycle (21 days) of treatment on dose level 1.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>LDE225 Plus Bortezomib</title>
          <description>Safety Lead-In: To determine the maximum tolerated dose (MTD), LDE225 will be administered orally at three dose levels: 400mg, 600mg, and 800mg.&#xD;
Bortezomib will be administered by subcutaneous injection (SQ) at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Expansion: Patients will receive LDE225 orally once daily for 21 days at the MTD. Bortezomib will be administered SQ at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Dose Escalation</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Cohort 1: LDE225 400mg</title>
              <participants_list>
                <participants group_id="P1" count="7">1 patient was found to be refractory to bortezomib and deemed ineligible.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Cohort 2: LDE225 600mg</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Cohort 3: LDE225 800mg</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4">Due to toxicity and lack of efficacy, no other dose levels were examined.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Dose-limiting toxicity</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Expansion</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Maintenance</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </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>LDE225 Plus Bortezomib</title>
          <description>Safety Lead-In: To determine the maximum tolerated dose (MTD), LDE225 will be administered orally at three dose levels: 400mg, 600mg, and 800mg.&#xD;
Bortezomib will be administered by subcutaneous injection (SQ) at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Expansion: Patients will receive LDE225 orally once daily for 21 days at the MTD. Bortezomib will be administered SQ at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="79" lower_limit="52" upper_limit="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African AMerican</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Tolerated Dose (MTD) of LDE225 Plus Bortezomib</title>
        <description>During the safety lead-in, a standard 3+3 dose escalation design was used to establish the MTD for LDE225 in combination with bortezomib. The MTD would be determined by the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during one cycle (21 days) of therapy. If 2 of 6 patients within a dose level experienced a DLT, that dose level would be defined as exceeding MTD and no further dose escalation would occur. The previous dose level would be considered the MTD.</description>
        <time_frame>every 3 weeks up to 48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>LDE225 Plus Bortezomib</title>
            <description>Safety Lead-In: To determine the maximum tolerated dose (MTD), LDE225 will be administered orally at three dose levels: 400mg, 600mg, and 800mg.&#xD;
Bortezomib will be administered by subcutaneous injection (SQ) at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Expansion: Patients will receive LDE225 orally once daily for 21 days at the MTD. Bortezomib will be administered SQ at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose (MTD) of LDE225 Plus Bortezomib</title>
          <description>During the safety lead-in, a standard 3+3 dose escalation design was used to establish the MTD for LDE225 in combination with bortezomib. The MTD would be determined by the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during one cycle (21 days) of therapy. If 2 of 6 patients within a dose level experienced a DLT, that dose level would be defined as exceeding MTD and no further dose escalation would occur. The previous dose level would be considered the MTD.</description>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">The MTD was not reached. Due to lack of efficacy and toxicity seen during dose level 1, additional dose levels were not examined and the study was terminated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to Disease Progression</title>
        <description>Time to progression (TTP) is measured from Day 1 of study drug administration to disease progression using International Myeloma Working Group (IMWG) Uniform Response Criteria.</description>
        <time_frame>every 3 weeks up to 48 weeks, then every 3 months thereafter up to 3 years from initiation of study treatment.</time_frame>
        <population>This outcome measure was to be assessed during the expansion phase of the study. The study closed early and did not proceed to this phase of the study. There is no data to report for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>LDE225 Plus Bortezomib</title>
            <description>Safety Lead-In: LDE225 will be administered orally at three dose levels: 400mg, 600mg, and 800mg for 21 days.&#xD;
Bortezomib will be administered by subcutaneous injection (SQ) at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Expansion: Patients will receive LDE225 orally once daily for 21 days at the MTD. Bortezomib will be administered SQ at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Disease Progression</title>
          <description>Time to progression (TTP) is measured from Day 1 of study drug administration to disease progression using International Myeloma Working Group (IMWG) Uniform Response Criteria.</description>
          <population>This outcome measure was to be assessed during the expansion phase of the study. The study closed early and did not proceed to this phase of the study. There is no data to report for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response</title>
        <description>Number of patients with confirmed Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Progressive Disease (PD) or Stable Disease (SD) according to International Myeloma Working Group (IMWG) Uniform Response Criteria. CR=5% or less plasma cells in bone marrow, disappearance of soft tissue plasmacytoma, negative immunofixation on serum and urine. VGPR=Serum and urine M-protein detectable by immunofixation but not by electrophoresis, disappearance of any soft tissue plasmacytomas that were present at baseline. PR= at least 50% reduction from baseline in serum M-protein and at least 90% reduction from baseline in 24hr urinary M-protein. PD=Increase of 25% or more from nadir in serum or urine proteins. SD= not meeting criteria for CR, VGPR, PR or PD.</description>
        <time_frame>Every 3 weeks up to 48 weeks</time_frame>
        <population>Of 7 enrolled patients, 1 was deemed ineligible and was excluded from efficacy analyses. At a median follow-up of 6 weeks, 3 patients in Cohort 1 had progressive disease and 3 had stable disease. Study was terminated after reviewing data from this first lead-in cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>LDE225 Plus Bortezomib</title>
            <description>Safety Lead-In: LDE225 will be administered orally at three dose levels: 400mg, 600mg, and 800mg for 21 days.&#xD;
Bortezomib will be administered by subcutaneous injection (SQ) at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Expansion: Patients will receive LDE225 orally once daily for 21 days at the MTD. Bortezomib will be administered SQ at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.&#xD;
Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response</title>
          <description>Number of patients with confirmed Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Progressive Disease (PD) or Stable Disease (SD) according to International Myeloma Working Group (IMWG) Uniform Response Criteria. CR=5% or less plasma cells in bone marrow, disappearance of soft tissue plasmacytoma, negative immunofixation on serum and urine. VGPR=Serum and urine M-protein detectable by immunofixation but not by electrophoresis, disappearance of any soft tissue plasmacytomas that were present at baseline. PR= at least 50% reduction from baseline in serum M-protein and at least 90% reduction from baseline in 24hr urinary M-protein. PD=Increase of 25% or more from nadir in serum or urine proteins. SD= not meeting criteria for CR, VGPR, PR or PD.</description>
          <population>Of 7 enrolled patients, 1 was deemed ineligible and was excluded from efficacy analyses. At a median follow-up of 6 weeks, 3 patients in Cohort 1 had progressive disease and 3 had stable disease. Study was terminated after reviewing data from this first lead-in cohort.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Progressive Disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stable Disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment-emergent adverse events were collected on Days 1 and 8 of every 21-day cycle for up to 48 weeks (plus 30 days for end of treatment visit).</time_frame>
      <desc>All patients who received at least one dose of LDE225 plus bortezomib.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1: LDE225 400mg/m^2</title>
          <description>Cohort 1 will receive LDE225 orally on a daily basis, at 400mg/m^2 every 21 days.&#xD;
Bortezomib will be administered by subcutaneous injection (SQ) at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2: LDE225 600mg/m^2</title>
          <description>Cohort 2 will receive LDE225 orally on a daily basis, at 600 mg every 21 days. Bortezomib will be administered by subcutaneous injection (SQ) at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.</description>
        </group>
        <group group_id="E3">
          <title>Cohort 3: LDE225 800mg/m^2</title>
          <description>Cohort 3 will receive LDE225 orally on a daily basis, at 800mg/m^2 every 21 days.&#xD;
Bortezomib will be administered by subcutaneous injection (SQ) at a fixed dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE 4.03</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="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral Gastroenteritis</sub_title>
                <description>Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events 4.03</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>NCI CTCAE 4.03</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="6" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title vocab="CTCAE 4.03">Thrombocytopenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Increased creatinine</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Decreased creatinine clearance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Cyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </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 sponsor can review/embargo results communications prior to public release for a period that is &gt;60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Early termination of study during dose-escalation did not support continuation of study.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Charles Davis, Sr Mgr Regulatory Strategy &amp; Operations</name_or_title>
      <organization>Sarah Cannon Development Innovations</organization>
      <phone>615-524-4341</phone>
      <email>charles.davis2@scri-innovations.com</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/NCT02254551
org study id: SCRI MM 50
nct id: NCT02254551
lead sponsor: 
collaborator: 
has dmc: No
The purpose of the study is to determine whether the combination of LDE225 (sonidegib) plus
      bortezomib is safe and effective in the treatment of relapsed or relapsed/refractory multiple
      myeloma.
Although multiple myeloma (MM) is considered fatal, survival has dramatically improved with
      the introduction of more effective treatment options. Despite these advances, all patients
      eventually relapse and MM is generally considered incurable. LDE225 (Sonidegib) is an oral,
      investigational smoothened (SMO) inhibitor that has shown anti-tumor activity in certain
      cancers. Bortezomib is a highly active drug for the treatment of MM and has produced response
      rates in relapsed and/or refractory patients. This study will investigate the tolerability
      and feasibility of combining LDE225 with bortezomib in patients with bortezomib-sensitive
      relapsed or relapsed/refractory MM.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) of LDE225 Plus Bortezomib
time frame: every 3 weeks up to 48 weeks
description: During the safety lead-in, a standard 3+3 dose escalation design was used to establish the MTD for LDE225 in combination with bortezomib. The MTD would be determined by the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during one cycle (21 days) of therapy. If 2 of 6 patients within a dose level experienced a DLT, that dose level would be defined as exceeding MTD and no further dose escalation would occur. The previous dose level would be considered the MTD.
measure: Time to Disease Progression
time frame: every 3 weeks up to 48 weeks, then every 3 months thereafter up to 3 years from initiation of study treatment.
description: Time to progression (TTP) is measured from Day 1 of study drug administration to disease progression using International Myeloma Working Group (IMWG) Uniform Response Criteria.
measure: Overall Response
time frame: Every 3 weeks up to 48 weeks
description: Number of patients with confirmed Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Progressive Disease (PD) or Stable Disease (SD) according to International Myeloma Working Group (IMWG) Uniform Response Criteria. CR=5% or less plasma cells in bone marrow, disappearance of soft tissue plasmacytoma, negative immunofixation on serum and urine. VGPR=Serum and urine M-protein detectable by immunofixation but not by electrophoresis, disappearance of any soft tissue plasmacytomas that were present at baseline. PR= at least 50% reduction from baseline in serum M-protein and at least 90% reduction from baseline in 24hr urinary M-protein. PD=Increase of 25% or more from nadir in serum or urine proteins. SD= not meeting criteria for CR, VGPR, PR or PD.
arm group label: LDE225 Plus Bortezomib
arm group type: Experimental
description: Lead-In Portion: The lead-in portion of this study will investigate the safety and tolerability, and determine the MTD of LDE225, in combination with bortezomib in this patient population.
Expansion Portion: Eligible patients will receive LDE225 orally once daily for 21 days with the dose-level determined in the lead-in portion of the study. Eligible patients will also receive a standard regimen of bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21 day cycle.
Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity.
intervention type: Drug
intervention name: LDE225
description: Lead-In: LDE225 will be administered orally at three dose levels starting at 400mg. If acceptable tolerability is demonstrated, escalations may continue up to 800 mg. LDE225 will be administered orally as a single daily dose for 21 days in combination with a fixed dose of bortezomib to be given on Days 1, 4, 8, 11 of each 21 day cycle.
Dose Expansion: LDE225 will be given as a single oral daily dose for 21 days at the MTD determined in the lead-in phase.
Maintenance Therapy: Patients who complete 16 cycles of therapy with stable disease or better will be eligible for single agent maintenance therapy of LDE225 at the MTD orally for up to 2 years or until progressive disease or unacceptable toxicity.
arm group label: LDE225 Plus Bortezomib
other name: Sonidegib
intervention type: Drug
intervention name: Bortezomib
description: In both the lead-in and dose expansion portions of the study, bortezomib, 1.3 mg/m2, will be administered by subcutaneous injection (SQ) on Days 1, 4, 8, 11 of each 21 day cycle.
arm group label: LDE225 Plus Bortezomib
other name: Velcade
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jesus G. Berdeja, M.D.
role: Study Chair
affiliation: SCRI Development Innovations, LLC
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Bortezomib
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Early termination of study during dose-escalation did not support continuation of study.
point of contact: 