<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/NCT01695330</url>
  </required_header>
  <id_info>
    <org_study_id>X05384</org_study_id>
    <nct_id>NCT01695330</nct_id>
  </id_info>
  <brief_title>Subcutaneous (SC) Bortezomib-Regimens for Patients With RR MM Failing Prior IV Bortezomib-Containing Regimens</brief_title>
  <official_title>A Phase II Study of Subcutaneous (SC) Bortezomib-Regimens for Patients With Relapsed/Refractory Multiple Myeloma (MM) Failing Prior Intravenous (IV) Bortezomib-Containing Regimens</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oncotherapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Millennium Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Oncotherapeutics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 2, multicenter, open label, nonrandomized study for patients with MM who will&#xD;
      receive treatment with a SC bortezomib-containing combination regimen that does not contain&#xD;
      thalidomide or vincristine. The patients will be required to have received a prior IV&#xD;
      bortezomib containing combination regimen that did not contain thalidomide or vincristine and&#xD;
      that differs from the SC bortezomib-containing one. In between the time that the patient&#xD;
      received the IV bortezomib-based combination regimen and enrollment onto this study, patients&#xD;
      may have received other non-bortezomib-based regimens as long as these treatments did not&#xD;
      contain thalidomide or vincristine. This study will enroll patients who have relapsed or have&#xD;
      become refractory to their prior IV-administered bortezomib-containing combination regimen as&#xD;
      demonstrated by progressive disease while on or following that regimen. Patients must have&#xD;
      received 4 doses of a minimum of 1.0 mg/m2 of bortezomib administered IV in no more than 4&#xD;
      weeks per cycle. Patients must have received at least one cycle meeting this definition and&#xD;
      have shown progressive disease to be considered eligible. Patients who have relapsed or have&#xD;
      become refractory to their most recent IV bortezomib-containing combination regimen are&#xD;
      eligible regardless of when they received that regimen, as long as they meet the above&#xD;
      criteria.&#xD;
&#xD;
      The study will consist of a screening period, followed by up to eight open label treatment&#xD;
      cycles, a final assessment to occur 28 days after the end of the last treatment cycle, and a&#xD;
      follow-up period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives:&#xD;
&#xD;
      • To establish the safety and tolerability of treatment with a SC bortezomib containing&#xD;
      combination regimen for MM patients who have demonstrated progressive disease from a prior&#xD;
      and different IV bortezomib containing combination regimen:&#xD;
&#xD;
        -  To compare the incidence of PN between IV bortezomib and treatment with SC bortezomib in&#xD;
           a subsequent anti-MM combination regimen&#xD;
&#xD;
        -  To compare the severity of PN between IV bortezomib and treatment with SC bortezomib in&#xD;
           a subsequent combination anti-MM regimen&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To compare the overall response rate [combined CR + very good partial response (VGPR) +&#xD;
           PR + MR] following treatment with a SC bortezomib-containing combination regimen for MM&#xD;
           patients who have demonstrated progressive disease from a prior and different IV&#xD;
           bortezomib containing combination regimen&#xD;
&#xD;
        -  To compare disease parameters following treatment with a SC bortezomib containing&#xD;
           combination regimen for MM patients who have demonstrated progressive disease from a&#xD;
           prior and different IV bortezomib containing combination regimen as follows:&#xD;
&#xD;
             -  time to progression&#xD;
&#xD;
             -  progression free survival&#xD;
&#xD;
             -  time to first response&#xD;
&#xD;
             -  duration of response&#xD;
&#xD;
             -  overall survival&#xD;
&#xD;
        -  To determine the incidence and severity of injection-site reactions with SC&#xD;
           administration of bortezomib&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated by Sponsor of this study.&#xD;
  </why_stopped>
  <start_date>May 2012</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>The Primary Objective of This Study Will be to Investigate the Incidence and Severity of Peripheral Neuropathy Caused by a Prior Intravenous VELCADE-containing Regimen in Comparison to That Caused by a Subcutaneous VELCADE-containing Regimen.</measure>
    <time_frame>Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.</time_frame>
    <description>Definition of incidence: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.&#xD;
Definition of severity: the severity of any treatment-emergent peripheral neuropathy experienced by a patient on-study. Peripheral neuropathy severity is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as the End of Study visit and is graded on a 0-4 scale based on CTCAE criteria.&#xD;
Incidence of Peripheral Neuropathy Definition: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare Overall Response Rate (CR + VGPR + PR + MR), Compare Disease Parameters, &amp; Determine Incidence and Severity of Injection-site Reactions.</measure>
    <time_frame>Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.</time_frame>
    <description>Compare overall response rate [combined CR + very good partial response (VGPR) + PR + MR] and disease parameters [time to progression, -progression free survival, -time to first response, -duration of response, -overall survival] following treatment with a SC bortezomib-containing combination regimen for MM patients who have demonstrated progressive disease form a prior or different IV bortezomib-containing combination regimen. Determine incidence and severity of injection-site reactions with CS administration of bortezomib by number of patients with injection site reaction specific adverse events.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Subcutaneous bortezomib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Subcutaneous bortezomib</intervention_name>
    <description>Bortezomib will be administered SC at a dose of 1.0 mg/m2. Doses are to be administered on days 1, 4, 8, and 11 of a 28-day cycle. All other drugs used in combination with the SC bortezomib as well as their doses and schedules will be at the discretion of the Principal Investigator.</description>
    <arm_group_label>Subcutaneous bortezomib</arm_group_label>
    <other_name>Velcade</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (Crit.):&#xD;
&#xD;
          1. Has a diagnosis of MM based on the following:&#xD;
&#xD;
             Major crit.:&#xD;
&#xD;
               1. plasmacytomas on tissue biopsy&#xD;
&#xD;
               2. bone marrow plasmacytosis (&gt; 30% plasma cells)&#xD;
&#xD;
               3. m-spike on serum electrophoresis IgG &gt; 3.5 g/dL or IgA &gt; 2.0 g/dL; kappa or&#xD;
                  lambda light chain excretion &gt; 1 g/day on 24 hour urine protein electrophoresis&#xD;
&#xD;
             Minor crit.:&#xD;
&#xD;
               1. bone marrow plasmacytosis (10% to 30% plasma cells)&#xD;
&#xD;
               2. monoclonal Ig present but of lesser magnitude than given under major crit.&#xD;
&#xD;
               3. lytic bone lesions&#xD;
&#xD;
               4. normal IgM &lt; 50 mg/dL, IgA &lt; 100 mg/dL, or IgG &lt; 600 mg/dL&#xD;
&#xD;
             Any of the following sets of crit. will confirm the diagnosis of MM:&#xD;
&#xD;
               -  any 2 of the major crit.&#xD;
&#xD;
               -  major criterion 1 plus minor criterion 2, 3, or 4&#xD;
&#xD;
               -  major criterion 3 plus minor criterion 1 or 3&#xD;
&#xD;
               -  minor crit. 1, 2, and 3, or 1, 2, and 4&#xD;
&#xD;
          2. MM with measurable disease, defined as:&#xD;
&#xD;
               -  a m-spike on serum electrophoresis of at least 0.5 g/dL and/or&#xD;
&#xD;
               -  urine monoclonal protein levels of at least 200 mg/24 hours&#xD;
&#xD;
               -  for patients without measurable serum and urine M-protein levels, an abnormal&#xD;
                  free light chain ratio (normal value: 0.26 - 1.65)&#xD;
&#xD;
          3. Currently has progressive MM:&#xD;
&#xD;
               -  Relapsed following stabilization or a response to at least one IV bortezomib&#xD;
                  (bort.) containing combination regimen that did not contain thalidomide or&#xD;
                  vincristine or refractory defined as progressed while receiving that anti-myeloma&#xD;
                  tx&#xD;
&#xD;
               -  In between the IV bort.-based combination regimen and this study, the pt may have&#xD;
                  received other non-bort.-based regimens as long as these treatments did not&#xD;
                  contain thalidomide or vincristine&#xD;
&#xD;
          4. Voluntary written informed consent before performance of any study-related procedure&#xD;
             not part of normal medical care&#xD;
&#xD;
          5. Age: ≥18 yrs at the time of consent&#xD;
&#xD;
          6. Able to adhere to the study visit schedule and other protocol requirements&#xD;
&#xD;
          7. ECOG performance status of ≤ 2 at study entry&#xD;
&#xD;
          8. Life-expectancy &gt; 3 mos&#xD;
&#xD;
          9. Laboratory test results w/in these ranges at Screening and confirmed at enrollment&#xD;
             prior to drug dosing on Cycle 1, Day 1:&#xD;
&#xD;
               -  ANC ≥ 1.5 x 109/L; if the bone marrow is extensively infiltrated (&gt; 70% plasma&#xD;
                  cells) then ≥ 1.0 x 109/L&#xD;
&#xD;
               -  Platelet count ≥ 75 x 109/L; if the bone marrow is extensively infiltrated (&gt; 70%&#xD;
                  plasma cells) then ≥ 50 x 109/L&#xD;
&#xD;
               -  Hgb &gt; 8 g/dL&#xD;
&#xD;
               -  Calculated or measured CrCl of at least 30 mL/min. (see protocol)&#xD;
&#xD;
               -  Total Bili ≥ 1.5 x ULN&#xD;
&#xD;
               -  AST (SGOT) and ALT (SGPT) ≥ 3 x ULN ≥ 5 x ULN if hepatic metastases are present&#xD;
&#xD;
               -  Serum potassium WNL&#xD;
&#xD;
         10. Female pt is either postmenopausal for 1 year or greater before the screening visit,&#xD;
             is surgically sterilized or if they are of childbearing potential, agree to practice 2&#xD;
             effective methods of contraception from the time of signing the informed consent form&#xD;
             through 30 days after the last dose of VELCADE, or agree to completely abstain from&#xD;
             heterosexual intercourse.&#xD;
&#xD;
         11. Male patients who agree to 1) practice effective barrier contraception during the&#xD;
             entire study treatment period and through a minimum of 30 days after the last dose of&#xD;
             study drug, or 2) completely abstain from heterosexual intercourse.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. POEMS syndrome&#xD;
&#xD;
          2. PCL&#xD;
&#xD;
          3. Primary amyloidosis&#xD;
&#xD;
          4. Diagnosed or treated for another malignancy w/in 3 yrs of enrollment, with the&#xD;
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of&#xD;
             the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.&#xD;
&#xD;
          5. ≤ Grade 2 peripheral neuropathy&#xD;
&#xD;
          6. Pt had myocardial infarction w/in 6 months prior to enrollment or has NYHA Class III&#xD;
             or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias,&#xD;
             or electrocardiographic evidence of acute ischemia or active conduction system&#xD;
             abnormalities.&#xD;
&#xD;
          7. Severe hypercalcemia, i.e., serum calcium ≤ 12 mg/dL (3.0 mmol/L) corrected for&#xD;
             albumin&#xD;
&#xD;
          8. Undergone major surgery w/in 28 days prior enrollment or has not recovered from side&#xD;
             effects of such therapy (see protocol)&#xD;
&#xD;
          9. Received the following prior therapy:&#xD;
&#xD;
               -  Thalidomide or vincristine alone or as part of a treatment regimen administered&#xD;
                  between the last IV bort.-based regimen and Cycle 1, Day 1 on this study.&#xD;
                  However, prior exposure to thalidomide or vincristine is allowed.&#xD;
&#xD;
               -  Chemotherapy w/in 21 days of study drugs (6 weeks for nitrosoureas)&#xD;
&#xD;
               -  Corticosteroids (&gt;10 mg/day prednisone or equivalent) w/in 21 days of study drugs&#xD;
                  unless steroids are being administered at that dose or greater as part of the new&#xD;
                  regimen&#xD;
&#xD;
               -  Immunotherapy or antibody therapy as well as lenalidomide, arsenic trioxide or&#xD;
                  bort. w/in 21 days before study drugs&#xD;
&#xD;
               -  Radiation therapy w/in 21 days before study drugs. (see protocol for exceptions)&#xD;
&#xD;
               -  Use of any other experimental drug or therapy w/in 28 days of study drugs&#xD;
&#xD;
         10. Participation in clinical trials with other investigational agents not included in&#xD;
             this trial, w/in 14 days of the start of this trial and throughout the duration of&#xD;
             this trial.&#xD;
&#xD;
         11. Hypersensitivity to VELCADE (bort.), boron, or mannitol.&#xD;
&#xD;
         12. Concurrent use of other anti-cancer agents or treatments&#xD;
&#xD;
         13. Pregnant or lactating patients&#xD;
&#xD;
         14. Serious medical or psychiatric illness&#xD;
&#xD;
         15. Known positivity for HIV or hepatitis B or C&#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>James R Berenson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>James R. Berenson, M.D., Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>James R. berenson, M.D., Inc.</name>
      <address>
        <city>West Hollywood</city>
        <state>California</state>
        <zip>90069</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>August 24, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <results_first_submitted>November 17, 2016</results_first_submitted>
  <results_first_submitted_qc>November 17, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 16, 2017</results_first_posted>
  <last_update_submitted>November 17, 2016</last_update_submitted>
  <last_update_submitted_qc>November 17, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 16, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Relapsed</keyword>
  <keyword>Refractory</keyword>
  <keyword>Bortezomib</keyword>
  <keyword>Subcutaneous</keyword>
  <keyword>Oncotherapeutics</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>Patients with MM who received treatment with a SC bortezomib-containing combination</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Subcutaneous Bortezomib</title>
          <description>patients with MM who received treatment with a SC bortezomib-containing combination. The patients were required to have received a prior IV bortezomib containing combination regimen that differs from the SC bortezomib-containing treatment.</description>
        </group>
        <group group_id="P2">
          <description>This is one-arm study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Subcutaneous Bortezomib</title>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" spread="5.1"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>The patients were required to have received a prior IV bortezomib containing combination regimen tha</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Primary Objective of This Study Will be to Investigate the Incidence and Severity of Peripheral Neuropathy Caused by a Prior Intravenous VELCADE-containing Regimen in Comparison to That Caused by a Subcutaneous VELCADE-containing Regimen.</title>
        <description>Definition of incidence: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.&#xD;
Definition of severity: the severity of any treatment-emergent peripheral neuropathy experienced by a patient on-study. Peripheral neuropathy severity is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as the End of Study visit and is graded on a 0-4 scale based on CTCAE criteria.&#xD;
Incidence of Peripheral Neuropathy Definition: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.</description>
        <time_frame>Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subcutaneous Bortezomib</title>
            <description>Patients with MM who received treatment with a SC bortezomib-containing combination</description>
          </group>
        </group_list>
        <measure>
          <title>The Primary Objective of This Study Will be to Investigate the Incidence and Severity of Peripheral Neuropathy Caused by a Prior Intravenous VELCADE-containing Regimen in Comparison to That Caused by a Subcutaneous VELCADE-containing Regimen.</title>
          <description>Definition of incidence: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.&#xD;
Definition of severity: the severity of any treatment-emergent peripheral neuropathy experienced by a patient on-study. Peripheral neuropathy severity is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as the End of Study visit and is graded on a 0-4 scale based on CTCAE criteria.&#xD;
Incidence of Peripheral Neuropathy Definition: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Compare Overall Response Rate (CR + VGPR + PR + MR), Compare Disease Parameters, &amp; Determine Incidence and Severity of Injection-site Reactions.</title>
        <description>Compare overall response rate [combined CR + very good partial response (VGPR) + PR + MR] and disease parameters [time to progression, -progression free survival, -time to first response, -duration of response, -overall survival] following treatment with a SC bortezomib-containing combination regimen for MM patients who have demonstrated progressive disease form a prior or different IV bortezomib-containing combination regimen. Determine incidence and severity of injection-site reactions with CS administration of bortezomib by number of patients with injection site reaction specific adverse events.</description>
        <time_frame>Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.</time_frame>
        <posting_date>10/2017</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Subcutaneous Bortezomib</title>
          <description>Bortezomib was administered SC at a dose of 1.0 mg/m2. Doses were administered on days 1, 4, 8, and 11 of a 28-day cycle. When administered subcutaneously, sites for each injection (thigh or abdomen) were rotated and reported. All other drugs used in combination with the SC bortezomib were recorded in the Case Report Forms along with their corresponding doses and schedules.</description>
        </group>
      </group_list>
      <serious_events>
        <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="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Gr3 Neturopenia</sub_title>
                <description>Neturopenia Gr3</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" 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>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. James Berenson</name_or_title>
      <organization>Oncotherapeutics</organization>
      <phone>310-420-9649</phone>
      <email>jberenson@berensonocology.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/NCT01695330
org study id: X05384
nct id: NCT01695330
lead sponsor: 
collaborator: 
has dmc: Yes
This is a phase 2, multicenter, open label, nonrandomized study for patients with MM who will
      receive treatment with a SC bortezomib-containing combination regimen that does not contain
      thalidomide or vincristine. The patients will be required to have received a prior IV
      bortezomib containing combination regimen that did not contain thalidomide or vincristine and
      that differs from the SC bortezomib-containing one. In between the time that the patient
      received the IV bortezomib-based combination regimen and enrollment onto this study, patients
      may have received other non-bortezomib-based regimens as long as these treatments did not
      contain thalidomide or vincristine. This study will enroll patients who have relapsed or have
      become refractory to their prior IV-administered bortezomib-containing combination regimen as
      demonstrated by progressive disease while on or following that regimen. Patients must have
      received 4 doses of a minimum of 1.0 mg/m2 of bortezomib administered IV in no more than 4
      weeks per cycle. Patients must have received at least one cycle meeting this definition and
      have shown progressive disease to be considered eligible. Patients who have relapsed or have
      become refractory to their most recent IV bortezomib-containing combination regimen are
      eligible regardless of when they received that regimen, as long as they meet the above
      criteria.

      The study will consist of a screening period, followed by up to eight open label treatment
      cycles, a final assessment to occur 28 days after the end of the last treatment cycle, and a
      follow-up period.
Primary Objectives:

      • To establish the safety and tolerability of treatment with a SC bortezomib containing
      combination regimen for MM patients who have demonstrated progressive disease from a prior
      and different IV bortezomib containing combination regimen:

        -  To compare the incidence of PN between IV bortezomib and treatment with SC bortezomib in
           a subsequent anti-MM combination regimen

        -  To compare the severity of PN between IV bortezomib and treatment with SC bortezomib in
           a subsequent combination anti-MM regimen

      Secondary Objectives:

        -  To compare the overall response rate [combined CR + very good partial response (VGPR) +
           PR + MR] following treatment with a SC bortezomib-containing combination regimen for MM
           patients who have demonstrated progressive disease from a prior and different IV
           bortezomib containing combination regimen

        -  To compare disease parameters following treatment with a SC bortezomib containing
           combination regimen for MM patients who have demonstrated progressive disease from a
           prior and different IV bortezomib containing combination regimen as follows:

             -  time to progression

             -  progression free survival

             -  time to first response

             -  duration of response

             -  overall survival

        -  To determine the incidence and severity of injection-site reactions with SC
           administration of bortezomib
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Primary Objective of This Study Will be to Investigate the Incidence and Severity of Peripheral Neuropathy Caused by a Prior Intravenous VELCADE-containing Regimen in Comparison to That Caused by a Subcutaneous VELCADE-containing Regimen.
time frame: Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.
description: Definition of incidence: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.
Definition of severity: the severity of any treatment-emergent peripheral neuropathy experienced by a patient on-study. Peripheral neuropathy severity is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as the End of Study visit and is graded on a 0-4 scale based on CTCAE criteria.
Incidence of Peripheral Neuropathy Definition: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.
measure: Compare Overall Response Rate (CR + VGPR + PR + MR), Compare Disease Parameters, & Determine Incidence and Severity of Injection-site Reactions.
time frame: Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.
description: Compare overall response rate [combined CR + very good partial response (VGPR) + PR + MR] and disease parameters [time to progression, -progression free survival, -time to first response, -duration of response, -overall survival] following treatment with a SC bortezomib-containing combination regimen for MM patients who have demonstrated progressive disease form a prior or different IV bortezomib-containing combination regimen. Determine incidence and severity of injection-site reactions with CS administration of bortezomib by number of patients with injection site reaction specific adverse events.
arm group label: Subcutaneous bortezomib
arm group type: Experimental
intervention type: Drug
intervention name: Subcutaneous bortezomib
description: Bortezomib will be administered SC at a dose of 1.0 mg/m2. Doses are to be administered on days 1, 4, 8, and 11 of a 28-day cycle. All other drugs used in combination with the SC bortezomib as well as their doses and schedules will be at the discretion of the Principal Investigator.
arm group label: Subcutaneous bortezomib
other name: Velcade
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James R Berenson, MD
role: Principal Investigator
affiliation: James R. Berenson, M.D., Inc.
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: 
point of contact: 