<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/NCT01706666</url>
  </required_header>
  <id_info>
    <org_study_id>MC1186</org_study_id>
    <secondary_id>NCI-2012-01579</secondary_id>
    <nct_id>NCT01706666</nct_id>
  </id_info>
  <brief_title>Bortezomib Based Consolidation in Multiple Myeloma Patients Completing Stem Cell Transplant</brief_title>
  <official_title>A Phase II Randomized Study of Three Subcutaneous Bortezomib-based Consolidation Treatments for Patients Completing Induction Therapy and Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II trial studies how well giving bortezomib with or without combination&#xD;
      chemotherapy works as consolidation therapy in patients with newly diagnosed multiple myeloma&#xD;
      who have completed stem cell transplant. Bortezomib may stop the growth of cancer cells by&#xD;
      blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as&#xD;
      cyclophosphamide, dexamethasone, and lenalidomide, work in different ways to stop the growth&#xD;
      of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet&#xD;
      known whether giving bortezomib is more effective with or without combination chemotherapy in&#xD;
      the post transplant setting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the stringent complete response (sCR) rate after 12 cycles among arms.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To compare progression-free and overall survival among arms. II. To describe the adverse&#xD;
      event profile of each arm.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To compare sCR after 6 cycles and 24 cycles and quality of life among arms.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 3 treatment arms.&#xD;
&#xD;
      ARM A: Patients receive bortezomib subcutaneously (SC) on days 1 and 15 of courses 1-12 and&#xD;
      day 1 of courses 13-24.&#xD;
&#xD;
      ARM B: Patients receive bortezomib SC as in Arm A, cyclophosphamide orally (PO) on days 1 and&#xD;
      15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of&#xD;
      courses 1-12 and day 1 of courses 13-24.&#xD;
&#xD;
      ARM C: Patients receive bortezomib SC as in Arm A and lenalidomide PO once daily (QD) on days&#xD;
      1-28.&#xD;
&#xD;
      In all arms, treatment continues every 28 days for up to 24 courses in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 6 months for 3 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 7, 2012</start_date>
  <completion_date type="Actual">May 17, 2016</completion_date>
  <primary_completion_date type="Actual">July 10, 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Patients Experiencing a Stringent Complete Response (sCR) After 12 Cycles, 24 Months</measure>
    <time_frame>24 months</time_frame>
    <description>Estimated by the number of sCRs divided by the total number of evaluable patients in each arm. Exact binomial confidence intervals for the true sCR rate will be calculated by arm. Stringent complete response (sCR) is defined as a complete response plus normal serum free light chain ratio and the absence of clonal cells in bone marrow by flow cytometry.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival Time</measure>
    <time_frame>From registration to death due to any cause, assessed up to 3 years</time_frame>
    <description>The distribution of survival time will be estimated by arm using the method of Kaplan-Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years</time_frame>
    <description>The distribution of progression-free survival will be estimated by arm using the method of Kaplan-Meier.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Stage I Multiple Myeloma</condition>
  <condition>Stage II Multiple Myeloma</condition>
  <condition>Stage III Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Arm A (bortezomib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (bortezomib, cyclophosphamide, dexamethasone)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive bortezomib SC as in Arm A, cyclophosphamide PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C (bortezomib, lenalidomide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bortezomib</intervention_name>
    <description>Given SC</description>
    <arm_group_label>Arm A (bortezomib)</arm_group_label>
    <arm_group_label>Arm B (bortezomib, cyclophosphamide, dexamethasone)</arm_group_label>
    <arm_group_label>Arm C (bortezomib, lenalidomide)</arm_group_label>
    <other_name>LDP 341</other_name>
    <other_name>MLN341</other_name>
    <other_name>VELCADE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cyclophosphamide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm B (bortezomib, cyclophosphamide, dexamethasone)</arm_group_label>
    <other_name>CPM</other_name>
    <other_name>CTX</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Endoxan</other_name>
    <other_name>Endoxana</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>lenalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm C (bortezomib, lenalidomide)</arm_group_label>
    <other_name>CC-5013</other_name>
    <other_name>IMiD-1</other_name>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm A (bortezomib)</arm_group_label>
    <arm_group_label>Arm B (bortezomib, cyclophosphamide, dexamethasone)</arm_group_label>
    <arm_group_label>Arm C (bortezomib, lenalidomide)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dexamethasone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm B (bortezomib, cyclophosphamide, dexamethasone)</arm_group_label>
    <other_name>Aeroseb-Dex</other_name>
    <other_name>Decaderm</other_name>
    <other_name>Decadron</other_name>
    <other_name>DM</other_name>
    <other_name>DXM</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>quality-of-life assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm A (bortezomib)</arm_group_label>
    <arm_group_label>Arm B (bortezomib, cyclophosphamide, dexamethasone)</arm_group_label>
    <arm_group_label>Arm C (bortezomib, lenalidomide)</arm_group_label>
    <other_name>quality of life assessment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Creatinine =&lt; 2 mg/dL&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000/mm^3&#xD;
&#xD;
          -  Platelet count &gt;= 75000/mm^3&#xD;
&#xD;
          -  Hemoglobin &gt;= 8.0 g/dL&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Treated myeloma: Prior induction therapy (any) and followed by autologous stem cell&#xD;
             transplantation&#xD;
&#xD;
          -  Measurable disease at initial diagnosis, pre-stem cell transplant (SCT) or post-SCT of&#xD;
             multiple myeloma as defined by at least ONE of the following:&#xD;
&#xD;
               -  Serum monoclonal protein &gt;= 0.5 g/dL&#xD;
&#xD;
               -  &gt; 200 mg of monoclonal protein in the urine on 24 hour electrophoresis&#xD;
&#xD;
               -  Serum immunoglobulin free light chain &gt;= 5 mg/dL AND abnormal serum&#xD;
                  immunoglobulin kappa to lambda free light chain ratio&#xD;
&#xD;
               -  Monoclonal bone marrow plasmacytosis &gt;= 30% (evaluable disease)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2&#xD;
&#xD;
          -  &lt; 120 days post SCT with no evidence of relapse or progression prior to registration&#xD;
&#xD;
          -  Provide voluntary informed written consent before performance of any study-related&#xD;
             procedure not part of normal medical care, with the understanding that consent may be&#xD;
             withdrawn by the subject at any time without prejudice to future medical care&#xD;
&#xD;
          -  Negative serum pregnancy test done =&lt; 7 days prior to registration, for women of&#xD;
             childbearing potential only&#xD;
&#xD;
          -  Willing to return to enrolling institution for follow-up during the active monitoring&#xD;
             phase of the study&#xD;
&#xD;
          -  Ability to complete questionnaire(s) by themselves or with assistance&#xD;
&#xD;
          -  Female patients who:&#xD;
&#xD;
               -  Are postmenopausal for at least 1 year before the screening visit, OR&#xD;
&#xD;
               -  Are surgically sterile, OR&#xD;
&#xD;
               -  If they are of childbearing potential, agree to practice 2 effective methods of&#xD;
                  contraception, at the same time, from the time of signing the informed consent&#xD;
                  through 30 days after the last dose of study treatment, OR agree to completely&#xD;
                  abstain from heterosexual intercourse&#xD;
&#xD;
          -  Male patients, even if surgically sterilized (ie, status postvasectomy), who:&#xD;
&#xD;
               -  Agree to practice effective barrier contraception during the entire study&#xD;
                  treatment period and through 30 days after the last dose of study treatment, OR&#xD;
&#xD;
               -  Agree to completely abstain from heterosexual intercourse&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other active malignancy =&lt; 3 years prior to registration; EXCEPTIONS: Non-melanotic&#xD;
             skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history of prior&#xD;
             malignancy, they must not be receiving other specific treatment for their cancer&#xD;
&#xD;
          -  Other co-morbidity which would interfere with patient's ability to participate in&#xD;
             trial, e.g. uncontrolled infection, uncompensated heart or lung disease&#xD;
&#xD;
          -  Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered&#xD;
             investigational; NOTE: Bisphosphonates are considered to be supportive care rather&#xD;
             than therapy, and are thus allowed while on protocol treatment&#xD;
&#xD;
          -  Known to be human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B&#xD;
             virus positive (HBV+)&#xD;
&#xD;
          -  Hypersensitivity to study drugs, boron or mannitol&#xD;
&#xD;
          -  Patient refractory to bortezomib (defined as patients who progressed while on&#xD;
             bortezomib or within 60 days of receiving bortezomib)&#xD;
&#xD;
          -  Any serious medical or psychiatric condition that would prevent the subject from&#xD;
             complying with the protocol treatment and procedures&#xD;
&#xD;
          -  Grade &gt;= 2 peripheral neuropathy&#xD;
&#xD;
          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart&#xD;
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe&#xD;
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute&#xD;
             ischemia or active conduction system abnormalities; prior to study entry, any&#xD;
             electrocardiogram (ECG) abnormality at screening must be documented by the&#xD;
             investigator as not medically relevant&#xD;
&#xD;
          -  Participation in clinical trials with other investigational agents not included in&#xD;
             this trial, within 14 days of the start of this trial and throughout the duration of&#xD;
             this trial&#xD;
&#xD;
          -  Radiation therapy within 3 weeks before randomization; enrollment of subjects who&#xD;
             require concurrent radiotherapy (which must be localized in its field size) should be&#xD;
             deferred until the radiotherapy is completed and 3 weeks have elapsed since the last&#xD;
             date of therapy&#xD;
&#xD;
          -  Female patients who are lactating or pregnant&#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>Craig B. Reeder, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287-8936</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Medical Center</name>
      <address>
        <city>Garland</city>
        <state>Texas</state>
        <zip>75042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>October 11, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2012</study_first_posted>
  <results_first_submitted>April 27, 2016</results_first_submitted>
  <results_first_submitted_qc>April 27, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 3, 2016</results_first_posted>
  <last_update_submitted>August 13, 2018</last_update_submitted>
  <last_update_submitted_qc>August 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Maintenance</keyword>
  <keyword>Consolidation</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>Dexamethasone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Bortezomib</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm A</title>
          <description>Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
        </group>
        <group group_id="P2">
          <title>Arm B</title>
          <description>Patients receive bortezomib SC as in Arm A, cyclophosphamide PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
        </group>
        <group group_id="P3">
          <title>Arm C</title>
          <description>Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm A</title>
          <description>Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
        </group>
        <group group_id="B2">
          <title>Arm B</title>
          <description>Patients receive bortezomib SC as in Arm A, cyclophosphamide PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
        </group>
        <group group_id="B3">
          <title>Arm C</title>
          <description>Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="1"/>
            <count group_id="B4" value="3"/>
          </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="54"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="50"/>
                    <measurement group_id="B4" value="50" lower_limit="45" upper_limit="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Had Prior Treatment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Patients Experiencing a Stringent Complete Response (sCR) After 12 Cycles, 24 Months</title>
        <description>Estimated by the number of sCRs divided by the total number of evaluable patients in each arm. Exact binomial confidence intervals for the true sCR rate will be calculated by arm. Stringent complete response (sCR) is defined as a complete response plus normal serum free light chain ratio and the absence of clonal cells in bone marrow by flow cytometry.</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Patients receive bortezomib SC as in Arm A, cyclophosphamide PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
          </group>
          <group group_id="O3">
            <title>Arm C</title>
            <description>Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Patients Experiencing a Stringent Complete Response (sCR) After 12 Cycles, 24 Months</title>
          <description>Estimated by the number of sCRs divided by the total number of evaluable patients in each arm. Exact binomial confidence intervals for the true sCR rate will be calculated by arm. Stringent complete response (sCR) is defined as a complete response plus normal serum free light chain ratio and the absence of clonal cells in bone marrow by flow cytometry.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Survival Time</title>
        <description>The distribution of survival time will be estimated by arm using the method of Kaplan-Meier.</description>
        <time_frame>From registration to death due to any cause, assessed up to 3 years</time_frame>
        <population>All patients are still alive</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Patients receive bortezomib SC as in Arm A, cyclophosphamide PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
          </group>
          <group group_id="O3">
            <title>Arm C</title>
            <description>Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.</description>
          </group>
        </group_list>
        <measure>
          <title>Survival Time</title>
          <description>The distribution of survival time will be estimated by arm using the method of Kaplan-Meier.</description>
          <population>All patients are still alive</population>
          <units>Months to death</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">No Deaths</measurement>
                    <measurement group_id="O2" value="NA">No Deaths</measurement>
                    <measurement group_id="O3" value="NA">No Deaths</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival</title>
        <description>The distribution of progression-free survival will be estimated by arm using the method of Kaplan-Meier.</description>
        <time_frame>From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Patients receive bortezomib SC as in Arm A, cyclophosphamide PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
          </group>
          <group group_id="O3">
            <title>Arm C</title>
            <description>Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>The distribution of progression-free survival will be estimated by arm using the method of Kaplan-Meier.</description>
          <units>Months to Progression</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">No progressions</measurement>
                    <measurement group_id="O2" value="9.2"/>
                    <measurement group_id="O3" value="NA">No progressions</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Arm A</title>
          <description>Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
        </group>
        <group group_id="E2">
          <title>Arm B</title>
          <description>Patients receive bortezomib SC as in Arm A, cyclophosphamide PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.</description>
        </group>
        <group group_id="E3">
          <title>Arm C</title>
          <description>Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 10</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 10</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="10" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="10" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="7" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="9" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="13" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="10" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="10" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="5" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="9" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Cystitis noninfective</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Craig B Reeder, MD</name_or_title>
      <organization>Mayo Clinic Cancer Center</organization>
      <phone>4803018335</phone>
      <email>Reeder.Craig@mayo.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01706666
org study id: MC1186
secondary id: NCI-2012-01579
nct id: NCT01706666
lead sponsor: 
has dmc: Yes
This randomized phase II trial studies how well giving bortezomib with or without combination
      chemotherapy works as consolidation therapy in patients with newly diagnosed multiple myeloma
      who have completed stem cell transplant. Bortezomib may stop the growth of cancer cells by
      blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as
      cyclophosphamide, dexamethasone, and lenalidomide, work in different ways to stop the growth
      of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet
      known whether giving bortezomib is more effective with or without combination chemotherapy in
      the post transplant setting.
PRIMARY OBJECTIVES:

      I. To compare the stringent complete response (sCR) rate after 12 cycles among arms.

      SECONDARY OBJECTIVES:

      I. To compare progression-free and overall survival among arms. II. To describe the adverse
      event profile of each arm.

      TERTIARY OBJECTIVES:

      I. To compare sCR after 6 cycles and 24 cycles and quality of life among arms.

      OUTLINE: Patients are randomized to 1 of 3 treatment arms.

      ARM A: Patients receive bortezomib subcutaneously (SC) on days 1 and 15 of courses 1-12 and
      day 1 of courses 13-24.

      ARM B: Patients receive bortezomib SC as in Arm A, cyclophosphamide orally (PO) on days 1 and
      15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of
      courses 1-12 and day 1 of courses 13-24.

      ARM C: Patients receive bortezomib SC as in Arm A and lenalidomide PO once daily (QD) on days
      1-28.

      In all arms, treatment continues every 28 days for up to 24 courses in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 months for 3 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of Patients Experiencing a Stringent Complete Response (sCR) After 12 Cycles, 24 Months
time frame: 24 months
description: Estimated by the number of sCRs divided by the total number of evaluable patients in each arm. Exact binomial confidence intervals for the true sCR rate will be calculated by arm. Stringent complete response (sCR) is defined as a complete response plus normal serum free light chain ratio and the absence of clonal cells in bone marrow by flow cytometry.
measure: Survival Time
time frame: From registration to death due to any cause, assessed up to 3 years
description: The distribution of survival time will be estimated by arm using the method of Kaplan-Meier.
measure: Progression-free Survival
time frame: From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years
description: The distribution of progression-free survival will be estimated by arm using the method of Kaplan-Meier.
arm group label: Arm A (bortezomib)
arm group type: Experimental
description: Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.
arm group label: Arm B (bortezomib, cyclophosphamide, dexamethasone)
arm group type: Experimental
description: Patients receive bortezomib SC as in Arm A, cyclophosphamide PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.
arm group label: Arm C (bortezomib, lenalidomide)
arm group type: Experimental
description: Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
intervention type: Drug
intervention name: bortezomib
description: Given SC
arm group label: Arm A (bortezomib)
arm group label: Arm B (bortezomib, cyclophosphamide, dexamethasone)
arm group label: Arm C (bortezomib, lenalidomide)
other name: LDP 341
other name: MLN341
other name: VELCADE
intervention type: Drug
intervention name: cyclophosphamide
description: Given PO
arm group label: Arm B (bortezomib, cyclophosphamide, dexamethasone)
other name: CPM
other name: CTX
other name: Cytoxan
other name: Endoxan
other name: Endoxana
intervention type: Drug
intervention name: lenalidomide
description: Given PO
arm group label: Arm C (bortezomib, lenalidomide)
other name: CC-5013
other name: IMiD-1
other name: Revlimid
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Arm A (bortezomib)
arm group label: Arm B (bortezomib, cyclophosphamide, dexamethasone)
arm group label: Arm C (bortezomib, lenalidomide)
intervention type: Drug
intervention name: dexamethasone
description: Given PO
arm group label: Arm B (bortezomib, cyclophosphamide, dexamethasone)
other name: Aeroseb-Dex
other name: Decaderm
other name: Decadron
other name: DM
other name: DXM
intervention type: Procedure
intervention name: quality-of-life assessment
description: Ancillary studies
arm group label: Arm A (bortezomib)
arm group label: Arm B (bortezomib, cyclophosphamide, dexamethasone)
arm group label: Arm C (bortezomib, lenalidomide)
other name: quality of life assessment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Craig B. Reeder, M.D.
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Cyclophosphamide
mesh term: Lenalidomide
mesh term: Bortezomib
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 