<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/NCT01675141</url>
  </required_header>
  <id_info>
    <org_study_id>120192</org_study_id>
    <secondary_id>12-C-0192</secondary_id>
    <nct_id>NCT01675141</nct_id>
  </id_info>
  <brief_title>Lenalidomide Maintenance Therapy for Multiple Myeloma</brief_title>
  <official_title>Lenalidomide Maintenance Therapy in Multiple Myeloma: A Phase II Clinical and Biomarker Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
        -  Multiple myeloma is rarely curable, but it is treatable. Initial treatment is directed&#xD;
           at controlling symptoms and reducing the number of myeloma cells. It continues until the&#xD;
           cancer stops responding to treatment. At that time, treatment may switch to maintenance&#xD;
           therapy, which is given to try to extend the response of the first therapy for as long&#xD;
           as possible. Research suggests that lenalidomide maintenance therapy may delay the time&#xD;
           for myeloma cells to start to grow and possibly improve survival.&#xD;
&#xD;
        -  Lenalidomide is a drug that may reduce or prevent the growth of cancer cells.&#xD;
           Researchers want to look at the long-term effect of lenalidomide on immune cells. It&#xD;
           will also look at the effects of extended treatment on the cancer and the immune system.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To test the long-term effectiveness of lenalidomide therapy for multiple myeloma.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Individuals at least 18 years of age with newly diagnosed or relapsed multiple myeloma.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a physical exam and medical history. Blood and urine&#xD;
           sample will be collected. A bone scan and bone marrow biopsy will also be performed.&#xD;
&#xD;
        -  Participants will receive lenalidomide maintenance treatment. It will be given according&#xD;
           to the standard of care for multiple myeloma. Participants will take lenalidomide every&#xD;
           day for 21 days of repeated 28-day cycles.&#xD;
&#xD;
        -  Treatment will be monitored with frequent blood tests. Blood tests will look at the&#xD;
           effect of the treatment on the immune system.&#xD;
&#xD;
        -  Treatment will continue as long as the cancer does not worsen and the side effects are&#xD;
           not severe.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Multiple myeloma (MM) remains largely an incurable disease with an estimated median survival&#xD;
      of 6-7 years in standard risk myeloma and 2-3 years in high risk disease despite treatment&#xD;
      with autologous stem cell transplantation (ASCT).&#xD;
&#xD;
      Maintenance therapy to achieve sustained suppression of residual disease following&#xD;
      chemotherapy or ASCT has long been viewed as a desirable approach for extending survival in&#xD;
      MM.&#xD;
&#xD;
      Giving the immunomodulatory drug lenalidomide after induction or re-induction treatment may&#xD;
      stimulate the immune system in various ways to stop or slow the return of cancer.&#xD;
&#xD;
      It is not yet known how immune stimulatory effects of extended dosing with lenalidomide in&#xD;
      the maintenance setting correlate with clinical benefits.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      Assess T cell (cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8),&#xD;
      natural killer T cell (NKT) and normal killer (NK) cell numbers in peripheral blood during&#xD;
      the&#xD;
&#xD;
      course of lenalidomide maintenance therapy in treated MM patients.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Patients with multiple myeloma who have achieved stable disease or better response, assessed&#xD;
      at greater than or equal to 4 weeks after completing induction or re-induction treatment&#xD;
&#xD;
      Age greater than or equal to 18 years&#xD;
&#xD;
      Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2&#xD;
&#xD;
      Adequate hematological parameters defined by: absolute neutrophil count greater than or equal&#xD;
      to 1.0 K/microL, hemoglobin greater than or equal to 8 g/dL, and platelet count greater than&#xD;
      or equal to 75 K/microL&#xD;
&#xD;
      Adequate hepatic function, with bilirubin &lt; 1.5 times the upper limit of normal (ULN), and&#xD;
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) &lt; 3 times ULN&#xD;
&#xD;
      Adequate renal function with creatinine clearance (CrCl) of greater than or equal to 40&#xD;
      mL/min. CrCl will be calculated using the Cockcroft-Gault method. If the calculated CrCl&#xD;
      based on Cockcroft-Gault method is &lt;40 mL/min, patient will have a 24 hr urine collection to&#xD;
      measure CrCl. The measured CrCl must also be greater than or equal to 40 ml/min&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Single arm, single stage, phase II trial of lenalidomide maintenance for treated MM patients&#xD;
      who have stable or responsive disease.&#xD;
&#xD;
      After screening, eligibility determination, and enrollment; subjects will receive&#xD;
      lenalidomide 10 mg by mouth daily on days 1-21 of repeated 28-day cycles. When necessary,&#xD;
      lenalidomide will be held and restarted in accordance with accepted clinical dose&#xD;
      modification guidelines.&#xD;
&#xD;
      Subjects may continue lenalidomide until disease progression or unacceptable toxicity or&#xD;
      completion of two years of lenalidomide therapy and the 30 day safety follow-up visit.&#xD;
&#xD;
      Blood will be obtained to assess changes in T cell (CD4, CD8), NKT and NK cell numbers by&#xD;
      flow-cytometric analysis at pre-specified time points during lenalidomide maintenance.&#xD;
&#xD;
      Blood samples and/or bone marrow samples where possible, will be used for additional research&#xD;
      studies, which may include functional analyses of immune-cell subsets, analyses for&#xD;
      cytokines, chemokines, antibodies, tumor cell antigen targets, and/or other markers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Original investigator left the NIH and the primary outcome was not reached&#xD;
  </why_stopped>
  <start_date type="Actual">August 20, 2012</start_date>
  <completion_date type="Actual">March 10, 2017</completion_date>
  <primary_completion_date type="Actual">May 5, 2016</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>Longitudinal Assessment of T Cell (Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8), Natural Killer T-cell (NKT) and Natural Killer (NK) Cell Counts</measure>
    <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
    <description>Peripheral blood samples will be collected to assess T cell (CD4, CD8), NKT and NK cell counts using flow cytometry.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Serious and Non-serious Adverse Events</measure>
    <time_frame>37 months and 12 days</time_frame>
    <description>Here is the number of serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
    <description>Duration of response is defined as time from response to disease progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be &gt;10mg/dl.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
    <description>PFS is defined as the time from study entry until progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be &gt;10mg/dl.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Natural Killer (NK) Cell Function and Activity</measure>
    <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
    <description>Percent of target cell lysis by NK cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in B Cell Subsets, Myeloid Derived Suppressor Cells and T Regulatory Cells by Phenotypic Analysis During the Course of Therapy</measure>
    <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
    <description>Percent change in total number of B Cell Subsets, Myeloid Derived Suppressor Cells and T Regulatory Cells by Phenotypic Analysis During the Course of Therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of Cereblon (CRBN) and How it Relates to Natural Killer (NK) Cell Number and Activity</measure>
    <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
    <description>Relative fold change in CRBN and correlation (R2) to NK cell number and activity.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Lenalidomide Maintenance Therapy for Multiple Myeloma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
    <arm_group_label>Lenalidomide Maintenance Therapy for Multiple Myeloma</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Patients with multiple myeloma treated with induction therapy or re-induction therapy,&#xD;
             who at the time of study enrollment have documented evidence of stable disease&#xD;
             response or better according to International Myeloma Workshop Consensus Panel. The&#xD;
             response assessment must occur at least 4 weeks after completion of their last&#xD;
             treatment.&#xD;
&#xD;
          -  Age greater than or equal to 18 years. Because no dosing or adverse event data are&#xD;
             currently available on the use of lenalidomide in patients&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.&#xD;
&#xD;
          -  Patient must have adequate hematologic, renal, hepatic, and cardiac function as&#xD;
             defined by:&#xD;
&#xD;
               -  Absolute neutrophil count greater than or equal to 1.0 K/microL independent of&#xD;
                  growth factor support&#xD;
&#xD;
               -  Platelets greater than or equal to 75K/microL&#xD;
&#xD;
               -  Hemoglobin greater than or equal to 8 g/dL (transfusions are permissible)&#xD;
&#xD;
               -  Calculated creatinine (CrCl) clearance of greater than or equal to 40 mL/min.&#xD;
                  using the Cockcroft-Gault method. If the calculated CrCl based on Cockcroft-Gault&#xD;
                  method is&#xD;
&#xD;
               -  Total bilirubin less than or equal to 1.5 mg/dL, aspartate aminotransferase&#xD;
                  (AST)/ serum glutamic oxaloacetic transaminase (SGOT) and alanine&#xD;
                  aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) less than or&#xD;
                  equal to 3 times ULN&#xD;
&#xD;
          -  Females of childbearing potential (FCBP) must agree to use two effective forms of&#xD;
             contraception simultaneously or to practice complete abstinence from heterosexual&#xD;
             intercourse during the following time periods related to this study: 1) for at least&#xD;
             28 days before starting study drug; 2) while participating in the study; and 3) for at&#xD;
             least 28 days after discontinuation from the study. The two methods of effective&#xD;
             contraception must include one highly effective method (i.e. intrauterine device&#xD;
             (IUD), hormonal [birth control pills, injections, or implants], tubal ligation,&#xD;
             partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom,&#xD;
             diaphragm, cervical cap). FCBP must be referred to a qualified provider of&#xD;
             contraceptive methods if needed.&#xD;
&#xD;
          -  A FCBP is defined as a sexually mature woman who: 1) has not undergone a hysterectomy&#xD;
             or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24&#xD;
             consecutive months (i.e., has had menses at any time in the preceding 24 consecutive&#xD;
             months).&#xD;
&#xD;
          -  A FCBP must have two negative serum or urine pregnancy tests prior to starting study&#xD;
             drug. The first pregnancy test must be performed within 10-14 days prior to the start&#xD;
             of study drug and the second pregnancy test must be performed within 24 hours prior to&#xD;
             prescribing the study drug. The prescriptions of study drug must be filled within 7&#xD;
             days.&#xD;
&#xD;
          -  Male patients must agree to use a latex condom during sexual contact with FCBP while&#xD;
             participating in the study and for at least 28 days following discontinuation from the&#xD;
             study even if he has undergone a successful vasectomy.&#xD;
&#xD;
          -  Patient must be able to take aspirin (81 or 325 mg) daily as prophylactic&#xD;
             anticoagulation. Patients intolerant to acetylsalicylic acid (ASA) may use warfarin or&#xD;
             low molecular weight heparin.&#xD;
&#xD;
          -  Patient must understand and voluntarily sign an informed consent form, with the&#xD;
             understanding that the patient may withdraw consent at any time without prejudice to&#xD;
             future medical care.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Patients with progressive or refractory multiple myeloma (MM), as defined by&#xD;
             International Myeloma Workshop Consensus Panel criteria.&#xD;
&#xD;
          -  Refractory to lenalidomide in the most recent line of therapy, as defined by the&#xD;
             International Myeloma Consensus Panel criteria - as failure to achieve minimal&#xD;
             response or development of progressive disease while on lenalidomide or within 30 days&#xD;
             of lenalidomide therapy&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents with the intent to treat&#xD;
             myeloma. Permitted concurrent therapies include:&#xD;
&#xD;
          -  Bisphosphonates&#xD;
&#xD;
          -  Radiotherapy to single stable disease site&#xD;
&#xD;
          -  Plasma cell leukemia&#xD;
&#xD;
          -  Pregnant or lactating females. Because there is a potential risk for adverse events to&#xD;
             nursing infants secondary to treatment of the mother with lenalidomide, lactating&#xD;
             females must agree not to breast feed while taking lenalidomide.&#xD;
&#xD;
          -  Uncontrolled hypertension or diabetes&#xD;
&#xD;
          -  Active hepatitis B or C infection&#xD;
&#xD;
          -  Diagnosed or treated for another malignancy within 3 years prior to study enrollment,&#xD;
             with the exception of complete resection of non-melanoma skin cancer, or an in situ&#xD;
             malignancy&#xD;
&#xD;
          -  Previous diagnosis of another malignancy with any evidence of residual disease.&#xD;
&#xD;
          -  Patients seropositive for the human immunodeficiency virus (HIV), and/or those who are&#xD;
             taking anti-retroviral treatment for HIV/acquired immune deficiency syndrome (AIDS)&#xD;
&#xD;
          -  Prior organ transplant requiring immunosuppressive therapy&#xD;
&#xD;
          -  Prior allogeneic stem cell transplant&#xD;
&#xD;
          -  Patients requiring continuous, systemic immunosuppressive therapy&#xD;
&#xD;
          -  Patients with myocardial infarction within 6 months prior to enrollment, New York&#xD;
             Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe&#xD;
             uncontrolled cardiac arrhythmias, or electrocardiographic evidence of acute ischemia&#xD;
&#xD;
          -  Patients with conditions that would prevent absorption of the study drug&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including but not limited to uncontrolled infection&#xD;
             or psychiatric illness/social situations that would compromise compliance with study&#xD;
             requirements&#xD;
&#xD;
          -  Significant neuropathy greater than or equal to Grade 3 at baseline&#xD;
&#xD;
          -  Contraindication to concomitant anticoagulation prophylaxis&#xD;
&#xD;
          -  Major surgery within 1 month prior to enrollment&#xD;
&#xD;
          -  Patients who were previously exposed and who developed severe adverse events,&#xD;
             hypersensitivity or desquamating rash to either thalidomide or lenalidomide&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dickran Kazandijicn, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center, 9000 Rockville Pike</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2012-C-0192.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004 Oct 28;351(18):1860-73. doi: 10.1056/NEJMra041875. No abstract available. Erratum In: N Engl J Med. 2005 Mar 17;352(11):1163.</citation>
    <PMID>15509819</PMID>
  </reference>
  <reference>
    <citation>Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, Dispenzieri A, Kumar S, Clark RJ, Baris D, Hoover R, Rajkumar SV. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009 May 28;113(22):5412-7. doi: 10.1182/blood-2008-12-194241. Epub 2009 Jan 29.</citation>
    <PMID>19179464</PMID>
  </reference>
  <reference>
    <citation>Rajkumar SV, Kyle RA. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc. 2005 Oct;80(10):1371-82. doi: 10.4065/80.10.1371.</citation>
    <PMID>16212152</PMID>
  </reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>August 25, 2012</study_first_submitted>
  <study_first_submitted_qc>August 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2012</study_first_posted>
  <results_first_submitted>April 4, 2017</results_first_submitted>
  <results_first_submitted_qc>April 4, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 12, 2017</results_first_posted>
  <last_update_submitted>January 8, 2018</last_update_submitted>
  <last_update_submitted_qc>January 8, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Institutes of Health Clinical Center (CC)</investigator_affiliation>
    <investigator_full_name>Dickran Kazandjian, M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>NK Cell Function</keyword>
  <keyword>Immunomodulatory Drugs</keyword>
  <keyword>T Cell Activity</keyword>
  <keyword>Immune Stimulatory Effects</keyword>
  <keyword>Extended Dosing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lenalidomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT01675141/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 6, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT01675141/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Lenalidomide Maintenance Therapy for Multiple Myeloma</title>
          <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.&#xD;
Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lenalidomide outside NIH</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>No treatment, per protocol</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lenalidomide Maintenance Therapy for Multiple Myeloma</title>
          <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.&#xD;
Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="57.05" spread="8.28"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Not Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mexican, Cuban, Puerto Rican, Central/So. American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Longitudinal Assessment of T Cell (Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8), Natural Killer T-cell (NKT) and Natural Killer (NK) Cell Counts</title>
        <description>Peripheral blood samples will be collected to assess T cell (CD4, CD8), NKT and NK cell counts using flow cytometry.</description>
        <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
        <population>This outcome was not done because this study was closed prior to full enrollment. Given study closure, the primary endpoint could not be and was not evaluated. There was not an adequate amount of specimens collected to arrive to any analyses conclusions.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenalidomide Maintenance Therapy for Multiple Myeloma</title>
            <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.&#xD;
Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Longitudinal Assessment of T Cell (Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8), Natural Killer T-cell (NKT) and Natural Killer (NK) Cell Counts</title>
          <description>Peripheral blood samples will be collected to assess T cell (CD4, CD8), NKT and NK cell counts using flow cytometry.</description>
          <population>This outcome was not done because this study was closed prior to full enrollment. Given study closure, the primary endpoint could not be and was not evaluated. There was not an adequate amount of specimens collected to arrive to any analyses conclusions.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Serious and Non-serious Adverse Events</title>
        <description>Here is the number of serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
        <time_frame>37 months and 12 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lenalidomide Maintenance Therapy for Multiple Myeloma</title>
            <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.&#xD;
Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious and Non-serious Adverse Events</title>
          <description>Here is the number of serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response</title>
        <description>Duration of response is defined as time from response to disease progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be &gt;10mg/dl.</description>
        <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lenalidomide Maintenance Therapy for Multiple Myeloma</title>
            <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.&#xD;
Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response</title>
          <description>Duration of response is defined as time from response to disease progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be &gt;10mg/dl.</description>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="0.9" upper_limit="NA">The median and upper limit of 95% CI is NR (not reached). The median and upper limit were not reached because there was not enough follow up time to reach a median or upper limit.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>PFS is defined as the time from study entry until progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be &gt;10mg/dl.</description>
        <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lenalidomide Maintenance Therapy for Multiple Myeloma</title>
            <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.&#xD;
Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>PFS is defined as the time from study entry until progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be &gt;10mg/dl.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="16.2" upper_limit="NA">The median and upper limit of 95% CI is NR (not reached). The median and upper limit were not reached because there was not enough follow up time to reach a median or upper limit.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Natural Killer (NK) Cell Function and Activity</title>
        <description>Percent of target cell lysis by NK cells</description>
        <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
        <population>This outcome was not done because this study was closed prior to full enrollment. Given study closure, the primary endpoint could not be and was not evaluated. There was not an adequate amount of specimens collected to arrive to any analyses conclusions.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenalidomide Maintenance Therapy for Multiple Myeloma</title>
            <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.&#xD;
Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Natural Killer (NK) Cell Function and Activity</title>
          <description>Percent of target cell lysis by NK cells</description>
          <population>This outcome was not done because this study was closed prior to full enrollment. Given study closure, the primary endpoint could not be and was not evaluated. There was not an adequate amount of specimens collected to arrive to any analyses conclusions.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in B Cell Subsets, Myeloid Derived Suppressor Cells and T Regulatory Cells by Phenotypic Analysis During the Course of Therapy</title>
        <description>Percent change in total number of B Cell Subsets, Myeloid Derived Suppressor Cells and T Regulatory Cells by Phenotypic Analysis During the Course of Therapy</description>
        <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
        <population>This outcome was not done because this study was closed prior to full enrollment. Given study closure, the primary endpoint could not be and was not evaluated. There was not an adequate amount of specimens collected to arrive to any analyses conclusions.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenalidomide Maintenance Therapy for Multiple Myeloma</title>
            <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.&#xD;
Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in B Cell Subsets, Myeloid Derived Suppressor Cells and T Regulatory Cells by Phenotypic Analysis During the Course of Therapy</title>
          <description>Percent change in total number of B Cell Subsets, Myeloid Derived Suppressor Cells and T Regulatory Cells by Phenotypic Analysis During the Course of Therapy</description>
          <population>This outcome was not done because this study was closed prior to full enrollment. Given study closure, the primary endpoint could not be and was not evaluated. There was not an adequate amount of specimens collected to arrive to any analyses conclusions.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expression of Cereblon (CRBN) and How it Relates to Natural Killer (NK) Cell Number and Activity</title>
        <description>Relative fold change in CRBN and correlation (R2) to NK cell number and activity.</description>
        <time_frame>participants were followed for the duration of their treatment, an average of 2 years</time_frame>
        <population>This outcome was not done because this study was closed prior to full enrollment. Given study closure, the primary endpoint could not be and was not evaluated. There was not an adequate amount of specimens collected to arrive to any analyses conclusions.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenalidomide Maintenance Therapy for Multiple Myeloma</title>
            <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.&#xD;
Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Expression of Cereblon (CRBN) and How it Relates to Natural Killer (NK) Cell Number and Activity</title>
          <description>Relative fold change in CRBN and correlation (R2) to NK cell number and activity.</description>
          <population>This outcome was not done because this study was closed prior to full enrollment. Given study closure, the primary endpoint could not be and was not evaluated. There was not an adequate amount of specimens collected to arrive to any analyses conclusions.</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>37 months and 12 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Lenalidomide Maintenance Therapy for Multiple Myeloma</title>
          <description>10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.&#xD;
Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="11"/>
              </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="11" subjects_affected="5" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, dental abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>CPK increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="11" subjects_affected="5" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="18" subjects_affected="8" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="25" subjects_affected="8" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="29" subjects_affected="10" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, primary prostate cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Postnasal drip</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Dickran Kazandijian</name_or_title>
      <organization>National Cancer Institute</organization>
      <phone>301-451-2677</phone>
      <email>kazandijiandg@nih.gov</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/NCT01675141
org study id: 120192
secondary id: 12-C-0192
nct id: NCT01675141
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Background:

        -  Multiple myeloma is rarely curable, but it is treatable. Initial treatment is directed
           at controlling symptoms and reducing the number of myeloma cells. It continues until the
           cancer stops responding to treatment. At that time, treatment may switch to maintenance
           therapy, which is given to try to extend the response of the first therapy for as long
           as possible. Research suggests that lenalidomide maintenance therapy may delay the time
           for myeloma cells to start to grow and possibly improve survival.

        -  Lenalidomide is a drug that may reduce or prevent the growth of cancer cells.
           Researchers want to look at the long-term effect of lenalidomide on immune cells. It
           will also look at the effects of extended treatment on the cancer and the immune system.

      Objectives:

      - To test the long-term effectiveness of lenalidomide therapy for multiple myeloma.

      Eligibility:

      - Individuals at least 18 years of age with newly diagnosed or relapsed multiple myeloma.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           sample will be collected. A bone scan and bone marrow biopsy will also be performed.

        -  Participants will receive lenalidomide maintenance treatment. It will be given according
           to the standard of care for multiple myeloma. Participants will take lenalidomide every
           day for 21 days of repeated 28-day cycles.

        -  Treatment will be monitored with frequent blood tests. Blood tests will look at the
           effect of the treatment on the immune system.

        -  Treatment will continue as long as the cancer does not worsen and the side effects are
           not severe.
Background:

      Multiple myeloma (MM) remains largely an incurable disease with an estimated median survival
      of 6-7 years in standard risk myeloma and 2-3 years in high risk disease despite treatment
      with autologous stem cell transplantation (ASCT).

      Maintenance therapy to achieve sustained suppression of residual disease following
      chemotherapy or ASCT has long been viewed as a desirable approach for extending survival in
      MM.

      Giving the immunomodulatory drug lenalidomide after induction or re-induction treatment may
      stimulate the immune system in various ways to stop or slow the return of cancer.

      It is not yet known how immune stimulatory effects of extended dosing with lenalidomide in
      the maintenance setting correlate with clinical benefits.

      Objectives:

      Assess T cell (cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8),
      natural killer T cell (NKT) and normal killer (NK) cell numbers in peripheral blood during
      the

      course of lenalidomide maintenance therapy in treated MM patients.

      Eligibility:

      Patients with multiple myeloma who have achieved stable disease or better response, assessed
      at greater than or equal to 4 weeks after completing induction or re-induction treatment

      Age greater than or equal to 18 years

      Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2

      Adequate hematological parameters defined by: absolute neutrophil count greater than or equal
      to 1.0 K/microL, hemoglobin greater than or equal to 8 g/dL, and platelet count greater than
      or equal to 75 K/microL

      Adequate hepatic function, with bilirubin < 1.5 times the upper limit of normal (ULN), and
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN

      Adequate renal function with creatinine clearance (CrCl) of greater than or equal to 40
      mL/min. CrCl will be calculated using the Cockcroft-Gault method. If the calculated CrCl
      based on Cockcroft-Gault method is <40 mL/min, patient will have a 24 hr urine collection to
      measure CrCl. The measured CrCl must also be greater than or equal to 40 ml/min

      Design:

      Single arm, single stage, phase II trial of lenalidomide maintenance for treated MM patients
      who have stable or responsive disease.

      After screening, eligibility determination, and enrollment; subjects will receive
      lenalidomide 10 mg by mouth daily on days 1-21 of repeated 28-day cycles. When necessary,
      lenalidomide will be held and restarted in accordance with accepted clinical dose
      modification guidelines.

      Subjects may continue lenalidomide until disease progression or unacceptable toxicity or
      completion of two years of lenalidomide therapy and the 30 day safety follow-up visit.

      Blood will be obtained to assess changes in T cell (CD4, CD8), NKT and NK cell numbers by
      flow-cytometric analysis at pre-specified time points during lenalidomide maintenance.

      Blood samples and/or bone marrow samples where possible, will be used for additional research
      studies, which may include functional analyses of immune-cell subsets, analyses for
      cytokines, chemokines, antibodies, tumor cell antigen targets, and/or other markers.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Longitudinal Assessment of T Cell (Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8), Natural Killer T-cell (NKT) and Natural Killer (NK) Cell Counts
time frame: participants were followed for the duration of their treatment, an average of 2 years
description: Peripheral blood samples will be collected to assess T cell (CD4, CD8), NKT and NK cell counts using flow cytometry.
measure: Number of Participants With Serious and Non-serious Adverse Events
time frame: 37 months and 12 days
description: Here is the number of serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
measure: Duration of Response
time frame: participants were followed for the duration of their treatment, an average of 2 years
description: Duration of response is defined as time from response to disease progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be >10mg/dl.
measure: Progression Free Survival (PFS)
time frame: participants were followed for the duration of their treatment, an average of 2 years
description: PFS is defined as the time from study entry until progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be >10mg/dl.
measure: Natural Killer (NK) Cell Function and Activity
time frame: participants were followed for the duration of their treatment, an average of 2 years
description: Percent of target cell lysis by NK cells
measure: Changes in B Cell Subsets, Myeloid Derived Suppressor Cells and T Regulatory Cells by Phenotypic Analysis During the Course of Therapy
time frame: participants were followed for the duration of their treatment, an average of 2 years
description: Percent change in total number of B Cell Subsets, Myeloid Derived Suppressor Cells and T Regulatory Cells by Phenotypic Analysis During the Course of Therapy
measure: Expression of Cereblon (CRBN) and How it Relates to Natural Killer (NK) Cell Number and Activity
time frame: participants were followed for the duration of their treatment, an average of 2 years
description: Relative fold change in CRBN and correlation (R2) to NK cell number and activity.
arm group label: Lenalidomide Maintenance Therapy for Multiple Myeloma
arm group type: Experimental
description: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Lenalidomide
description: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.
arm group label: Lenalidomide Maintenance Therapy for Multiple Myeloma
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Dickran Kazandijicn, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2012-C-0192.html
description: NIH Clinical Center Detailed Web Page
citation: Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004 Oct 28;351(18):1860-73. doi: 10.1056/NEJMra041875. No abstract available. Erratum In: N Engl J Med. 2005 Mar 17;352(11):1163.
PMID: 15509819
citation: Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, Dispenzieri A, Kumar S, Clark RJ, Baris D, Hoover R, Rajkumar SV. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009 May 28;113(22):5412-7. doi: 10.1182/blood-2008-12-194241. Epub 2009 Jan 29.
PMID: 19179464
citation: Rajkumar SV, Kyle RA. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc. 2005 Oct;80(10):1371-82. doi: 10.4065/80.10.1371.
PMID: 16212152
responsible party type: Principal Investigator
investigator affiliation: National Institutes of Health Clinical Center (CC)
investigator full name: Dickran Kazandjian, M.D.
investigator title: Principal Investigator
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Lenalidomide
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 