<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/NCT01729338</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00038924</org_study_id>
    <secondary_id>Millennium</secondary_id>
    <nct_id>NCT01729338</nct_id>
  </id_info>
  <brief_title>Velcade + Cyclophosphamide in Newly Diagnosed Multiple Myeloma</brief_title>
  <official_title>Phase II Subcutaneous VELCADE and Oral Cyclophosphamide-based Induction + Sequential VELCADE and Revlimid Maintenance for Newly Diagnosed Multiple Myeloma in Non-transplant Candidates: An Entirely Non-intravenous Regimen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Millennium Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Duke Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary purpose of this study is to estimate the overall response rate (ORR), defined as&#xD;
      partial response (PR) or better at any time during induction therapy. The success of the&#xD;
      therapy will be determined by ORR with strong consideration given to the secondary endpoints&#xD;
      of tolerability, duration of response, and quality of life (QOL).&#xD;
&#xD;
      All patients will be treated with the same experimental regimen. Several novel features are&#xD;
      being explored: the substitution of cyclophosphamide for melphalan; once weekly AND&#xD;
      subcutaneous bortezomib instead of standard twice weekly, intravenous dosing; and alternating&#xD;
      bortezomib and lenalidomide in maintenance.&#xD;
&#xD;
      The investigators hypothesize that this regimen will prove to be tolerable and effective in&#xD;
      inducing and maintaining remission in a patient population that is historically very&#xD;
      difficult to treat, namely Multiple Myeloma (MM) patients who are too elderly or suffer&#xD;
      comorbidities, such as renal insufficiency, that otherwise complicate aggressive therapies&#xD;
      like autologous stem-cell transplantation (ASCT). In short, the investigators view this as&#xD;
      the &quot;Multiple Myeloma trial for non-trial candidates.&quot;&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 35 patients will be accrued to this single arm, open label, phase II trial over a&#xD;
      period of about 18 months, studying induction chemotherapy with VELCADE, cyclophosphamide and&#xD;
      dexamethasone administered on an attenuated dosing schedule to accommodate non-candidates for&#xD;
      high-dose chemotherapy with autologous stem cell transplantation - an often frail patient&#xD;
      population. Maintenance therapy will follow with alternating lenalidomide and VELCADE. All&#xD;
      patients should receive antiviral (zoster) prophylaxis, and peptic ulcer prophylaxis is&#xD;
      recommended. Aspirin and/or anticoagulation are left to study physician discretion. All&#xD;
      patients will be treated with the same experimental regimen. Several novel features are being&#xD;
      explored: the substitution of cyclophosphamide for melphalan; once weekly AND subcutaneous&#xD;
      bortezomib instead of standard twice weekly, intravenous dosing; and alternating bortezomib&#xD;
      and lenalidomide in maintenance. The overarching aim is to preserve efficacy while minimizing&#xD;
      toxicity and inconvenience to this often frail patient population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">December 19, 2012</start_date>
  <completion_date type="Actual">December 31, 2016</completion_date>
  <primary_completion_date type="Actual">December 31, 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>Overall Response Rate (ORR) During Induction Therapy</measure>
    <time_frame>Up to 8 months</time_frame>
    <description>Defined as percentage of patients achieving a partial response or better by International Myeloma Working Group (IMWG) standard criteria:&#xD;
IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and &lt;5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, &gt;90% in serum M-protein+urine, M-protein level &lt;100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or &lt;200 mg/24hour.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Severe Adverse Event Rate</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Defined as number of patients experiencing any grade or severe (≥ grade 3 by common toxicity criteria for adverse events (CTCAE) v4.0 criteria) adverse events at any time during the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Depth of Response During Induction Therapy</measure>
    <time_frame>Up to 8 months</time_frame>
    <description>Maximum depth of response is defined as: ranging from partial response to complete response by International Myeloma Working Group (IMWG). Described as number of patients achieving each level of response. IMWG: CR: negative immunofixation on the serum and urine, no soft tissue plasmacytomas and &lt;5% plasma cells in the bone marrow; sCR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR: serum and urine M-protein detected by immunofixation but not electrophoresis, &gt;90% in serum M-protein+urine, M-protein level &lt;100 mg/24hour; PR: ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or &lt;200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Depth of Response During Maintenance Therapy</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Defined as maximum depth of response (ranging from partial response to complete response by International Myeloma Working Group (IMWG) criteria at any point during post-induction maintenance therapy.&#xD;
IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and &lt;5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, &gt;90% in serum M-protein+urine, M-protein level &lt;100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or &lt;200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Time to Response</measure>
    <time_frame>Up to 8 months</time_frame>
    <description>Defined as median time to achievement of response (partial remission or better by International Myeloma Working Group standard criteria), in study subjects during 8 months of induction chemotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Duration of Response</measure>
    <time_frame>From date of first confirmed response until date of disease progression or up to 3 years</time_frame>
    <description>Defined as median time elapsed in study subjects between achievement of response and disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Progression-free Survival</measure>
    <time_frame>4 years</time_frame>
    <description>Defined as median time elapsed in study subjects between initiation of study therapy and either disease progression or death, regardless of cause of death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Overall Survival</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Defined as median time elapsed in study subjects between initiation of study therapy and death, regardless of cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QLQ-C30 Question 29</measure>
    <time_frame>baseline, 3 months, 5 months</time_frame>
    <description>Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 29: how would you rate your overall health during the past week? 7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QLQ-C30 Question 30</measure>
    <time_frame>baseline, 3 months, 5 months</time_frame>
    <description>Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 30: How would you rate your overall quality of life during the past week?&#xD;
7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functionality as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool</measure>
    <time_frame>baseline</time_frame>
    <description>Mean functionality in study subjects, quantitatively scored using the standardized and validated Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool, which comprehensively assesses aspects of a patient's functionality such as symptoms (e.g., pain, anxiety), social support (e.g., someone to turn to for help), and ability to carry out routine activities (e.g., grocery shopping) or physical exertion (e.g., climbing stairs) was assessed at baseline.&#xD;
The score is obtained by inserting patient-specific data into the online calculator found at http://www.mycarg.org/Chemo_Toxicity_Calculator, which is based on the risk score described in Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457-3465.&#xD;
The risk score ranges from 0-19, with 0-5 indicating low risk, 6-9 intermediate risk, and 10-19 high risk for severe (grade &gt;2) toxicity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Risk Score as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool</measure>
    <time_frame>Day 1</time_frame>
    <description>Calculation of the risk score requires that the patient be assessed with the CALGB Assessment Tool, which has both a patient self-reporting questionnaire and a clinician assessment. Both will be used in this trial, and thus patients will have risk scores based on their own self-assessments and risk scores based on the clinicians' assessment. The risk score ranges from 0-19, with 0-5 indicating low risk, 6-9 intermediate risk, and 10-19 high risk. The distribution of the risk score in this trial will be described by plotting the median of the risk score against time, with patient and clinician assessments overlaid on the same plot.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Velcade, cyclophosphamide, Revlimid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Velcade</intervention_name>
    <description>Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until disease progression, lack of tolerability, or death. Patients who cannot tolerate SC VELCADE will be converted to the same dose, given intravenously (IV), per discretion of the treating physician.</description>
    <arm_group_label>Velcade, cyclophosphamide, Revlimid</arm_group_label>
    <other_name>bortezomib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide: 300 mg/m2, given orally on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Patients who cannot swallow cyclophosphamide pills will be converted to the same dose, given intravenously (IV).</description>
    <arm_group_label>Velcade, cyclophosphamide, Revlimid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Revlimid</intervention_name>
    <description>Lenalidomide (odd cycles [9,11,13, etc.]: 10 mg, given orally on days 1-21. Maintenance cycles will last 28 days and continue indefinitely, until disease progression, lack of tolerability, or death. On even cycles, patients will be prescribed enough lenalidomide to take at home, as instructed, for one cycle. This will be prescribed through the mandatory RevlimidREMS® program. If a dose of lenalidomide is missed, it should be taken as soon as possible on the same day. If it is missed for the entire day, it should not be made up.&#xD;
Patients who take more than the prescribed dose of lenalidomide should be instructed to seek emergency medical care if needed and contact study staff immediately.</description>
    <arm_group_label>Velcade, cyclophosphamide, Revlimid</arm_group_label>
    <other_name>lenalidomide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Voluntary written informed consent before performance of any study-related procedure&#xD;
             not part of normal medical care, with the understanding that consent may be withdrawn&#xD;
             by the subject at any time without prejudice to future medical care.&#xD;
&#xD;
          -  Age ≥18 years at the time of signing the informed consent form.&#xD;
&#xD;
          -  Able to adhere to the study visit schedule and other protocol requirements.&#xD;
&#xD;
          -  Multiple Myeloma (MM) diagnosed according to the following standard criteria (all&#xD;
             three criteria must be met):&#xD;
&#xD;
               -  Monoclonal plasma cells in bone marrow ≥10% and/or presence of biopsy-proven&#xD;
                  plasmacytoma&#xD;
&#xD;
               -  Laboratory tests meet the levels specified in the protocol&#xD;
&#xD;
          -  Measurable disease requiring systemic therapy.&#xD;
&#xD;
          -  No prior systemic therapy or radiation therapy active against myeloma lasting more&#xD;
             than four weeks duration. Any prior therapy must be completed a minimum of 21 days&#xD;
             before starting study drugs. Enrollment of subjects who require radiotherapy (which&#xD;
             must be localized in its field size) should be deferred until the radiotherapy is&#xD;
             completed and 3 weeks have elapsed since the last date of therapy.&#xD;
&#xD;
          -  Karnofsky performance status (KPS) of ≥ 60% at study entry.&#xD;
&#xD;
          -  In order to obtain lenalidomide, patients must be registered into the mandatory&#xD;
             RevlimidREMS® program during the maintenance phase of therapy, and be willing and able&#xD;
             to comply with the requirements of RevlimidREMS®&#xD;
&#xD;
          -  Female subjects must be postmenopausal for at least 1 year before the screening visit&#xD;
             or surgically sterilized. If females are of childbearing potential, they must adhere&#xD;
             to required pregnancy testing; male and female subjects must use specified effective&#xD;
             birth control methods.&#xD;
&#xD;
          -  Patients should receive concomitant therapy with bisphosphonates, regardless of the&#xD;
             presence of bony lesions, although study physicians may use their discretion based on&#xD;
             presence of renal insufficiency or other mitigating factors.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Abnormal laboratory tests within the ranges specified in the protocol&#xD;
&#xD;
          -  Serum creatinine will not be used to exclude patients. Patients on renal-replacement&#xD;
             therapy (e.g., hemodialysis or peritoneal dialysis) will be eligible to participate.&#xD;
&#xD;
          -  Light-chain (AL) amyloidosis. Patients with secondary amyloidosis due to MM are&#xD;
             eligible.&#xD;
&#xD;
          -  ≥ Grade 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;
             Electrocardiography (ECG) abnormality at screening must be documented by the&#xD;
             investigator as not medically relevant.&#xD;
&#xD;
          -  Hypersensitivity to VELCADE, boron, mannitol, or any other component of protocol&#xD;
             therapy.&#xD;
&#xD;
          -  Female subject is pregnant or lactating. Confirmation that the subject is not pregnant&#xD;
             must be established by a negative serum beta-human chorionic gonadotropin (b- hCG)&#xD;
             pregnancy test result obtained during screening as specified in section 7.11.&#xD;
&#xD;
          -  Female patients who are lactating or have a positive serum pregnancy test during the&#xD;
             screening period, or a positive urine pregnancy test on Day 1 before first dose of&#xD;
             study drug, if applicable.&#xD;
&#xD;
          -  Serious medical or psychiatric illness likely to interfere with participation in this&#xD;
             clinical study.&#xD;
&#xD;
          -  Diagnosed or treated for another malignancy within 2 years 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;
          -  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;
          -  Concurrent use of other anti-cancer agents or treatments&#xD;
&#xD;
          -  Known HIV positivity&#xD;
&#xD;
          -  Known active hepatitis A, 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>Gwynn Long, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>November 14, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <results_first_submitted>December 19, 2016</results_first_submitted>
  <results_first_submitted_qc>April 26, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 31, 2017</results_first_posted>
  <last_update_submitted>April 26, 2017</last_update_submitted>
  <last_update_submitted_qc>April 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 31, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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>Cyclophosphamide</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Bortezomib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>17 subjects consented to the study. 1 subject was a screen failure.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Velcade, Cyclophosphamide, Revlimid</title>
          <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Velcade, Cyclophosphamide, Revlimid</title>
          <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="76.5" spread="6.7"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR) During Induction Therapy</title>
        <description>Defined as percentage of patients achieving a partial response or better by International Myeloma Working Group (IMWG) standard criteria:&#xD;
IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and &lt;5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, &gt;90% in serum M-protein+urine, M-protein level &lt;100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or &lt;200 mg/24hour.</description>
        <time_frame>Up to 8 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) During Induction Therapy</title>
          <description>Defined as percentage of patients achieving a partial response or better by International Myeloma Working Group (IMWG) standard criteria:&#xD;
IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and &lt;5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, &gt;90% in serum M-protein+urine, M-protein level &lt;100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or &lt;200 mg/24hour.</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="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Severe Adverse Event Rate</title>
        <description>Defined as number of patients experiencing any grade or severe (≥ grade 3 by common toxicity criteria for adverse events (CTCAE) v4.0 criteria) adverse events at any time during the study</description>
        <time_frame>Up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>Severe Adverse Event Rate</title>
          <description>Defined as number of patients experiencing any grade or severe (≥ grade 3 by common toxicity criteria for adverse events (CTCAE) v4.0 criteria) adverse events at any time during the study</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="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Depth of Response During Induction Therapy</title>
        <description>Maximum depth of response is defined as: ranging from partial response to complete response by International Myeloma Working Group (IMWG). Described as number of patients achieving each level of response. IMWG: CR: negative immunofixation on the serum and urine, no soft tissue plasmacytomas and &lt;5% plasma cells in the bone marrow; sCR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR: serum and urine M-protein detected by immunofixation but not electrophoresis, &gt;90% in serum M-protein+urine, M-protein level &lt;100 mg/24hour; PR: ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or &lt;200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease.</description>
        <time_frame>Up to 8 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Depth of Response During Induction Therapy</title>
          <description>Maximum depth of response is defined as: ranging from partial response to complete response by International Myeloma Working Group (IMWG). Described as number of patients achieving each level of response. IMWG: CR: negative immunofixation on the serum and urine, no soft tissue plasmacytomas and &lt;5% plasma cells in the bone marrow; sCR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR: serum and urine M-protein detected by immunofixation but not electrophoresis, &gt;90% in serum M-protein+urine, M-protein level &lt;100 mg/24hour; PR: ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or &lt;200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease.</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="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very good partial response (VGPR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Complete Response/Stringent complete response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease/no response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Depth of Response During Maintenance Therapy</title>
        <description>Defined as maximum depth of response (ranging from partial response to complete response by International Myeloma Working Group (IMWG) criteria at any point during post-induction maintenance therapy.&#xD;
IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and &lt;5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, &gt;90% in serum M-protein+urine, M-protein level &lt;100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or &lt;200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>8 of all subjects reached maintenance and could be analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Depth of Response During Maintenance Therapy</title>
          <description>Defined as maximum depth of response (ranging from partial response to complete response by International Myeloma Working Group (IMWG) criteria at any point during post-induction maintenance therapy.&#xD;
IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and &lt;5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, &gt;90% in serum M-protein+urine, M-protein level &lt;100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or &lt;200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease.</description>
          <population>8 of all subjects reached maintenance and could be analyzed</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very good partial response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Complete Response/Stringent complete response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease/no response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Time to Response</title>
        <description>Defined as median time to achievement of response (partial remission or better by International Myeloma Working Group standard criteria), in study subjects during 8 months of induction chemotherapy.</description>
        <time_frame>Up to 8 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>Median Time to Response</title>
          <description>Defined as median time to achievement of response (partial remission or better by International Myeloma Working Group standard criteria), in study subjects during 8 months of induction chemotherapy.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" spread="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Duration of Response</title>
        <description>Defined as median time elapsed in study subjects between achievement of response and disease progression.</description>
        <time_frame>From date of first confirmed response until date of disease progression or up to 3 years</time_frame>
        <population>9 out of all patients achieved response and hence could be analyzed for duration of response</population>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>Median Duration of Response</title>
          <description>Defined as median time elapsed in study subjects between achievement of response and disease progression.</description>
          <population>9 out of all patients achieved response and hence could be analyzed for duration of response</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.2" spread="0.207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Progression-free Survival</title>
        <description>Defined as median time elapsed in study subjects between initiation of study therapy and either disease progression or death, regardless of cause of death.</description>
        <time_frame>4 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>Median Progression-free Survival</title>
          <description>Defined as median time elapsed in study subjects between initiation of study therapy and either disease progression or death, regardless of cause of death.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.2" spread="0.157"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Overall Survival</title>
        <description>Defined as median time elapsed in study subjects between initiation of study therapy and death, regardless of cause.</description>
        <time_frame>Up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>Median Overall Survival</title>
          <description>Defined as median time elapsed in study subjects between initiation of study therapy and death, regardless of cause.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.7" spread="0.189"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>QLQ-C30 Question 29</title>
        <description>Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 29: how would you rate your overall health during the past week? 7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality.</description>
        <time_frame>baseline, 3 months, 5 months</time_frame>
        <population>Participants who completed questionnaire.</population>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>QLQ-C30 Question 29</title>
          <description>Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 29: how would you rate your overall health during the past week? 7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality.</description>
          <population>Participants who completed questionnaire.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.3" spread="22.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65" spread="18.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>5 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.3" spread="15.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.45</p_value>
            <p_value_desc>Compared baseline to 3 months</p_value_desc>
            <method>paired t-test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.19</p_value>
            <method>paired t-test</method>
            <method_desc>compares baseline to month 5</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>QLQ-C30 Question 30</title>
        <description>Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 30: How would you rate your overall quality of life during the past week?&#xD;
7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality.</description>
        <time_frame>baseline, 3 months, 5 months</time_frame>
        <population>Participants who completed questionnaire.</population>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>QLQ-C30 Question 30</title>
          <description>Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 30: How would you rate your overall quality of life during the past week?&#xD;
7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality.</description>
          <population>Participants who completed questionnaire.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.7" spread="24.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.7" spread="19.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>5 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.7" spread="12.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1</p_value>
            <p_value_desc>baseline, 3 month</p_value_desc>
            <method>paired t-test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.09</p_value>
            <method>paired t-test</method>
            <method_desc>baseline, month 5</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Functionality as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool</title>
        <description>Mean functionality in study subjects, quantitatively scored using the standardized and validated Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool, which comprehensively assesses aspects of a patient's functionality such as symptoms (e.g., pain, anxiety), social support (e.g., someone to turn to for help), and ability to carry out routine activities (e.g., grocery shopping) or physical exertion (e.g., climbing stairs) was assessed at baseline.&#xD;
The score is obtained by inserting patient-specific data into the online calculator found at http://www.mycarg.org/Chemo_Toxicity_Calculator, which is based on the risk score described in Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457-3465.&#xD;
The risk score ranges from 0-19, with 0-5 indicating low risk, 6-9 intermediate risk, and 10-19 high risk for severe (grade &gt;2) toxicity.</description>
        <time_frame>baseline</time_frame>
        <population>Participants who completed functionality assessment at baseline. Data were incompletely and irregularly collected after baseline so unable to analyze additional time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>Functionality as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool</title>
          <description>Mean functionality in study subjects, quantitatively scored using the standardized and validated Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool, which comprehensively assesses aspects of a patient's functionality such as symptoms (e.g., pain, anxiety), social support (e.g., someone to turn to for help), and ability to carry out routine activities (e.g., grocery shopping) or physical exertion (e.g., climbing stairs) was assessed at baseline.&#xD;
The score is obtained by inserting patient-specific data into the online calculator found at http://www.mycarg.org/Chemo_Toxicity_Calculator, which is based on the risk score described in Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457-3465.&#xD;
The risk score ranges from 0-19, with 0-5 indicating low risk, 6-9 intermediate risk, and 10-19 high risk for severe (grade &gt;2) toxicity.</description>
          <population>Participants who completed functionality assessment at baseline. Data were incompletely and irregularly collected after baseline so unable to analyze additional time points.</population>
          <units>Scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Risk Score as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool</title>
        <description>Calculation of the risk score requires that the patient be assessed with the CALGB Assessment Tool, which has both a patient self-reporting questionnaire and a clinician assessment. Both will be used in this trial, and thus patients will have risk scores based on their own self-assessments and risk scores based on the clinicians' assessment. The risk score ranges from 0-19, with 0-5 indicating low risk, 6-9 intermediate risk, and 10-19 high risk. The distribution of the risk score in this trial will be described by plotting the median of the risk score against time, with patient and clinician assessments overlaid on the same plot.</description>
        <time_frame>Day 1</time_frame>
        <population>Data for the risk score wasn't recorded correctly, and therefore we were unable to analyze the data.</population>
        <group_list>
          <group group_id="O1">
            <title>Velcade, Cyclophosphamide, Revlimid</title>
            <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
          </group>
        </group_list>
        <measure>
          <title>Risk Score as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool</title>
          <description>Calculation of the risk score requires that the patient be assessed with the CALGB Assessment Tool, which has both a patient self-reporting questionnaire and a clinician assessment. Both will be used in this trial, and thus patients will have risk scores based on their own self-assessments and risk scores based on the clinicians' assessment. The risk score ranges from 0-19, with 0-5 indicating low risk, 6-9 intermediate risk, and 10-19 high risk. The distribution of the risk score in this trial will be described by plotting the median of the risk score against time, with patient and clinician assessments overlaid on the same plot.</description>
          <population>Data for the risk score wasn't recorded correctly, and therefore we were unable to analyze the data.</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_list>

    <reported_events>
      <time_frame>1st day of drug till 30 days after last dose</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Velcade, Cyclophosphamide, Revlimid</title>
          <description>INDUCTION (28-day cycles for 8 cycles):&#xD;
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15&#xD;
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15&#xD;
Dexamethasone 40 mg PO days 1,8 and 15&#xD;
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):&#xD;
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21&#xD;
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15&#xD;
Velcade: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>NCI CTCAE v4</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="9" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle weakness upper limb</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>NCI CTCAE v4</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="14" subjects_at_risk="14"/>
              </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="19" subjects_affected="7" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other, specify</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="12" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="20" subjects_affected="8" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="11" subjects_affected="5" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="11" subjects_affected="5" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="10" subjects_affected="8" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="15" subjects_affected="8" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Immune system disorders - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, specify</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Libido decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Psychiatric disorders - Other, specify</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, specify</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Urinary urgency</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="14" subjects_affected="5" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Postnasal drip</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Bullous dermatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="16" subjects_affected="8" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nail loss</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Purpura</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Vascular disorders - Other, specify</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </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>Gwynn Long</name_or_title>
      <organization>Duke University Medical Center</organization>
      <phone>919-668-0838</phone>
      <email>gwynn.long@duke.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/NCT01729338
org study id: Pro00038924
secondary id: Millennium
nct id: NCT01729338
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The primary purpose of this study is to estimate the overall response rate (ORR), defined as
      partial response (PR) or better at any time during induction therapy. The success of the
      therapy will be determined by ORR with strong consideration given to the secondary endpoints
      of tolerability, duration of response, and quality of life (QOL).

      All patients will be treated with the same experimental regimen. Several novel features are
      being explored: the substitution of cyclophosphamide for melphalan; once weekly AND
      subcutaneous bortezomib instead of standard twice weekly, intravenous dosing; and alternating
      bortezomib and lenalidomide in maintenance.

      The investigators hypothesize that this regimen will prove to be tolerable and effective in
      inducing and maintaining remission in a patient population that is historically very
      difficult to treat, namely Multiple Myeloma (MM) patients who are too elderly or suffer
      comorbidities, such as renal insufficiency, that otherwise complicate aggressive therapies
      like autologous stem-cell transplantation (ASCT). In short, the investigators view this as
      the "Multiple Myeloma trial for non-trial candidates."
A total of 35 patients will be accrued to this single arm, open label, phase II trial over a
      period of about 18 months, studying induction chemotherapy with VELCADE, cyclophosphamide and
      dexamethasone administered on an attenuated dosing schedule to accommodate non-candidates for
      high-dose chemotherapy with autologous stem cell transplantation - an often frail patient
      population. Maintenance therapy will follow with alternating lenalidomide and VELCADE. All
      patients should receive antiviral (zoster) prophylaxis, and peptic ulcer prophylaxis is
      recommended. Aspirin and/or anticoagulation are left to study physician discretion. All
      patients will be treated with the same experimental regimen. Several novel features are being
      explored: the substitution of cyclophosphamide for melphalan; once weekly AND subcutaneous
      bortezomib instead of standard twice weekly, intravenous dosing; and alternating bortezomib
      and lenalidomide in maintenance. The overarching aim is to preserve efficacy while minimizing
      toxicity and inconvenience to this often frail patient population.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR) During Induction Therapy
time frame: Up to 8 months
description: Defined as percentage of patients achieving a partial response or better by International Myeloma Working Group (IMWG) standard criteria:
IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and <5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, >90% in serum M-protein+urine, M-protein level <100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or <200 mg/24hour.
measure: Severe Adverse Event Rate
time frame: Up to 3 years
description: Defined as number of patients experiencing any grade or severe (≥ grade 3 by common toxicity criteria for adverse events (CTCAE) v4.0 criteria) adverse events at any time during the study
measure: Maximum Depth of Response During Induction Therapy
time frame: Up to 8 months
description: Maximum depth of response is defined as: ranging from partial response to complete response by International Myeloma Working Group (IMWG). Described as number of patients achieving each level of response. IMWG: CR: negative immunofixation on the serum and urine, no soft tissue plasmacytomas and <5% plasma cells in the bone marrow; sCR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR: serum and urine M-protein detected by immunofixation but not electrophoresis, >90% in serum M-protein+urine, M-protein level <100 mg/24hour; PR: ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or <200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease.
measure: Maximum Depth of Response During Maintenance Therapy
time frame: Up to 3 years
description: Defined as maximum depth of response (ranging from partial response to complete response by International Myeloma Working Group (IMWG) criteria at any point during post-induction maintenance therapy.
IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and <5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, >90% in serum M-protein+urine, M-protein level <100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or <200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease.
measure: Median Time to Response
time frame: Up to 8 months
description: Defined as median time to achievement of response (partial remission or better by International Myeloma Working Group standard criteria), in study subjects during 8 months of induction chemotherapy.
measure: Median Duration of Response
time frame: From date of first confirmed response until date of disease progression or up to 3 years
description: Defined as median time elapsed in study subjects between achievement of response and disease progression.
measure: Median Progression-free Survival
time frame: 4 years
description: Defined as median time elapsed in study subjects between initiation of study therapy and either disease progression or death, regardless of cause of death.
measure: Median Overall Survival
time frame: Up to 3 years
description: Defined as median time elapsed in study subjects between initiation of study therapy and death, regardless of cause.
measure: QLQ-C30 Question 29
time frame: baseline, 3 months, 5 months
description: Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 29: how would you rate your overall health during the past week? 7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality.
measure: QLQ-C30 Question 30
time frame: baseline, 3 months, 5 months
description: Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 30: How would you rate your overall quality of life during the past week?
7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality.
measure: Functionality as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool
time frame: baseline
description: Mean functionality in study subjects, quantitatively scored using the standardized and validated Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool, which comprehensively assesses aspects of a patient's functionality such as symptoms (e.g., pain, anxiety), social support (e.g., someone to turn to for help), and ability to carry out routine activities (e.g., grocery shopping) or physical exertion (e.g., climbing stairs) was assessed at baseline.
The score is obtained by inserting patient-specific data into the online calculator found at http://www.mycarg.org/Chemo_Toxicity_Calculator, which is based on the risk score described in Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457-3465.
The risk score ranges from 0-19, with 0-5 indicating low risk, 6-9 intermediate risk, and 10-19 high risk for severe (grade >2) toxicity.
measure: Risk Score as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool
time frame: Day 1
description: Calculation of the risk score requires that the patient be assessed with the CALGB Assessment Tool, which has both a patient self-reporting questionnaire and a clinician assessment. Both will be used in this trial, and thus patients will have risk scores based on their own self-assessments and risk scores based on the clinicians' assessment. The risk score ranges from 0-19, with 0-5 indicating low risk, 6-9 intermediate risk, and 10-19 high risk. The distribution of the risk score in this trial will be described by plotting the median of the risk score against time, with patient and clinician assessments overlaid on the same plot.
arm group label: Velcade, cyclophosphamide, Revlimid
arm group type: Experimental
description: INDUCTION (28-day cycles for 8 cycles):
VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15
Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15
Dexamethasone 40 mg PO days 1,8 and 15
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):
Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21
Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15
intervention type: Drug
intervention name: Velcade
description: Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until disease progression, lack of tolerability, or death. Patients who cannot tolerate SC VELCADE will be converted to the same dose, given intravenously (IV), per discretion of the treating physician.
arm group label: Velcade, cyclophosphamide, Revlimid
other name: bortezomib
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide: 300 mg/m2, given orally on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Patients who cannot swallow cyclophosphamide pills will be converted to the same dose, given intravenously (IV).
arm group label: Velcade, cyclophosphamide, Revlimid
intervention type: Drug
intervention name: Revlimid
description: Lenalidomide (odd cycles [9,11,13, etc.]: 10 mg, given orally on days 1-21. Maintenance cycles will last 28 days and continue indefinitely, until disease progression, lack of tolerability, or death. On even cycles, patients will be prescribed enough lenalidomide to take at home, as instructed, for one cycle. This will be prescribed through the mandatory RevlimidREMS® program. If a dose of lenalidomide is missed, it should be taken as soon as possible on the same day. If it is missed for the entire day, it should not be made up.
Patients who take more than the prescribed dose of lenalidomide should be instructed to seek emergency medical care if needed and contact study staff immediately.
arm group label: Velcade, cyclophosphamide, Revlimid
other name: lenalidomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gwynn Long, MD
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Cyclophosphamide
mesh term: Lenalidomide
mesh term: Bortezomib
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 