<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/NCT03030261</url>
  </required_header>
  <id_info>
    <org_study_id>201701084</org_study_id>
    <secondary_id>CA204-225</secondary_id>
    <secondary_id>PO-CL-MM-PI-008341</secondary_id>
    <nct_id>NCT03030261</nct_id>
  </id_info>
  <brief_title>Elotuzumab, Pomalidomide, &amp; Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma</brief_title>
  <official_title>A Phase II Study of Elotuzumab, Pomalidomide, &amp; Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</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>
      Based on the need to improve outcomes post second autologous stem cell transplant (ASCT) for&#xD;
      multiple myeloma (MM) and the benefits seen of maintenance treatment following initial ASCT,&#xD;
      the natural next step is to evaluate maintenance/continuation therapy following second ASCT.&#xD;
&#xD;
      Pomalidomide is active against MM cells refractory to both bortezomib and lenalidomide,&#xD;
      making it an ideal choice for continuation therapy following second ASCT. Adding elotuzumab&#xD;
      may increase efficacy and also the durability of responses which is essential to improving&#xD;
      outcomes following second ASCT.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 22, 2017</start_date>
  <completion_date type="Anticipated">September 26, 2027</completion_date>
  <primary_completion_date type="Actual">September 29, 2022</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>Event-free survival (EFS) rate</measure>
    <time_frame>1 year</time_frame>
    <description>-Event-free survival (EFS) will be defined as time from ASCT to disease progression, relapse, or death, whichever occurs first. Patients who are removed from study therapy prior to any of these events occurring will be censored at the time of initiation of subsequent anti-myeloma treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>Through completion of treatment (estimated to be 102 weeks)</time_frame>
    <description>-Overall response rate (ORR) will be defined as the proportion of evaluable patients meeting the criteria for partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete response rate (CRR)</measure>
    <time_frame>Through completion of treatment (estimated to be 102 weeks)</time_frame>
    <description>Complete response rate (CRR) will be defined as the proportion of evaluable patients meeting the criteria complete (CR) or stringent complete response (sCR)&#xD;
Stringent complete response (sCR) requires all of the following:&#xD;
CR as defined below&#xD;
Normal free light chain ratio (0.26-1.65)&#xD;
Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence&#xD;
Complete response (CR) requires all of the following:&#xD;
Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine&#xD;
If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)&#xD;
&lt;5% plasma cells in the bone marrow&#xD;
Disappearance of soft tissue plasmacytoma&#xD;
Patients who do not meet the definition of CR based solely on residual monoclonal protein on serum electrophoresis and/or immunofixation, but are MRD-negative as described above, will also be considered CR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival (EFS)</measure>
    <time_frame>Up to 5 years post completion of treatment</time_frame>
    <description>-Event-free survival (EFS) will be defined as time from ASCT to disease progression, relapse, or death, whichever occurs first. Patients who are removed from study therapy prior to any of these events occurring will be censored at the time of initiation of subsequent anti-myeloma treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Up to 5 years post completion of treatment</time_frame>
    <description>-Progression-free survival (PFS) will be defined as time from ASCT to disease progression or relapse. Any patient who expires or withdraws prior to disease progression or relapse will be censored at last follow-up. Patients who are removed from study therapy prior to progression or relapse will be censored at the time of initiation of subsequent anti-myeloma treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 5 years post completion of treatment</time_frame>
    <description>-Overall survival (OS) will be defined as time from ASCT to death due to any causes. Patients who are alive at the time of data analyses will be censored on the last known alive date. Patients who are removed from study therapy prior death will be censored at the time of initiation of subsequent anti-myeloma treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity of regimen as measured by frequency of adverse events per the number of participants treated</measure>
    <time_frame>Up to 30 days following completion of treatment (estimated to be 106 weeks)</time_frame>
    <description>-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Multiple Myeloma in Relapse</condition>
  <arm_group>
    <arm_group_label>Elotuzumab + Pomalidomide + Dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will undergo standard of care ASCT melphalan conditioning. Administration of melphalan and the second ASCT will be done as part of routine care and procedures are not dictated by this protocol.&#xD;
Continuation therapy with Elo-Pom-Dex will begin between Days 80 and 120 following the second ASCT:&#xD;
Elotuzumab on Days 1 and 15 for Cycles 1-6 followed by 20 mg/kg on Day 1 for Cycles 7+&#xD;
Pomalidomide daily on Days 1-21 of all cycles&#xD;
Dexamethasone on Days 1 and 15 of all cycles&#xD;
Continuation therapy may continue until relapse or progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Elotuzumab</intervention_name>
    <description>During continuation therapy, elotuzumab will be administered on a 28-day cycle as follows: on Days 1 and 15 for Cycles 1-6 and on Day 1 for Cycles 7+. For Cycles 1-6 elotuzumab will be administered intravenously at a dose of 10 mg/kg. For Cycles 7+ elotuzumab will be administered at a dose of 20 mg/kg.</description>
    <arm_group_label>Elotuzumab + Pomalidomide + Dexamethasone</arm_group_label>
    <other_name>Empliciti</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pomalidomide</intervention_name>
    <description>During continuation therapy, pomalidomide will be taken by mouth daily on Days 1-21 of each 28-day cycle at a starting dose of 2 mg. During continuation, pomalidomide may be dose escalated to 4 mg at the discretion of the treating physician if the 2 mg dose is tolerated.</description>
    <arm_group_label>Elotuzumab + Pomalidomide + Dexamethasone</arm_group_label>
    <other_name>Pomalyst</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>During continuation therapy, dexamethasone will be taken by mouth at a starting dose of 40 mg. It will be given on a 28-day cycle as follows: on Days 1 and 15 for Cycles 1-6 and on Day 1 only for Cycles 7+. Sufficient quantity of drug for one cycle of therapy will be prescribed to the patient at a time.</description>
    <arm_group_label>Elotuzumab + Pomalidomide + Dexamethasone</arm_group_label>
    <other_name>Decadron</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed diagnosis of multiple myeloma.&#xD;
&#xD;
          -  Received prior autologous stem cell transplantation as first line therapy for multiple&#xD;
             myeloma with subsequent disease relapse/progression.&#xD;
&#xD;
          -  Failed 1 or 2 lines of treatment for multiple myeloma. A line of treatment includes&#xD;
             all therapy including induction, transplant, and maintenance administered in a&#xD;
             sequence in the absence of relapse/progression. Once relapse/progression occurs and&#xD;
             subsequently the anti-myeloma treatment is changed, a new line of treatment has begun.&#xD;
             Local radiation or corticosteroids will not be considered treatment for multiple&#xD;
             myeloma.&#xD;
&#xD;
          -  Received 2 to 6 cycles of induction therapy per standard of care prior to 2nd&#xD;
             autologous stem cell transplantation&#xD;
&#xD;
          -  Received standard of care melphalan conditioning for 2nd autologous stem cell&#xD;
             transplantation, is currently Day +80 to +120 following transplant, and is responding&#xD;
             to therapy (partial response or better as compared to pre-induction assessment.&#xD;
&#xD;
          -  All US study participants must be registered into the mandatory POMALYST REMS® program&#xD;
             and be willing and able to comply with the requirements of the POMALYST REMS® program.&#xD;
             For Canadian sites, patients will followed according to the Pomalidomide pregnancy&#xD;
             prevention program&#xD;
&#xD;
          -  Females of reproductive potential within the US must agree to adhere to the scheduled&#xD;
             pregnancy testing as required in the POMALYST REMS® program. For Canadian sites,&#xD;
             patients will followed according to the Pomalidomide pregnancy prevention program&#xD;
&#xD;
          -  At least 18 and no more than 75 years of age at enrollment.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2&#xD;
&#xD;
          -  Normal bone marrow and organ function as defined as ALL of the following:&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1000/mm^3&#xD;
&#xD;
               -  Platelets ≥ 75,000/mm^3 (transfusions not permitted within 7 days of screening)&#xD;
&#xD;
               -  Total bilirubin ≤ 2.0 x institutional upper limit of normal (IULN)&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN&#xD;
&#xD;
               -  Creatinine clearance ≥ 15 mL/min&#xD;
&#xD;
          -  Females of childbearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control, abstinence) prior to study entry through&#xD;
             Day +100 visit. Should a woman become pregnant or suspect she is pregnant while&#xD;
             participating in this study, she must inform her treating physician immediately.&#xD;
&#xD;
          -  Able to understand and willing to sign an Institutional Review Board (IRB) approved&#xD;
             written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refractory to elotuzumab and/or pomalidomide, defined as progressive disease or&#xD;
             clinical relapse on therapy or within 60 days following completion of therapy. Prior&#xD;
             exposure to elotuzumab and/or pomalidomide is allowed as long as patient is not&#xD;
             refractory to these agents.&#xD;
&#xD;
          -  More than one prior transplant prior to study entry with the exception of tandem&#xD;
             transplantation. Tandem transplantation is defined as two autologous stem cell&#xD;
             transplants that occur within 9 months of one another, and the patient did not have&#xD;
             disease progression in the period between the two transplants.&#xD;
&#xD;
          -  Presence of peripheral neuropathy ≥ grade 3 based on National Cancer Institute (NCI)&#xD;
             Common Terminology Criteria for Adverse Events (CTCAE) v 4.0&#xD;
&#xD;
          -  History of plasma cell leukemia or MM central nervous system (CNS) involvement.&#xD;
&#xD;
          -  Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.&#xD;
&#xD;
          -  Diagnosed with another concurrent malignancy requiring treatment.&#xD;
&#xD;
          -  Known HIV or active hepatitis A, B, or C. Antidoby testing not required for screening&#xD;
&#xD;
          -  Known hypersensitivity to pomalidomide, dexamethasone, or any excipients in&#xD;
             elotuzumab, formulation, or recombinant protein&#xD;
&#xD;
          -  Receiving any other investigational agents within 14 days prior to enrollment.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac&#xD;
             arrhythmia.&#xD;
&#xD;
          -  Pregnant and/or breastfeeding. Females of childbearing potential must have two&#xD;
             negative pregnancy tests. The first test should be performed within 10-14 days of&#xD;
             study entry, and the second test within 24 hours prior to prescribing pomalidomide.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ravi Vij, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Colorado Blood Cancer Institute (Sarah Cannon)</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Health Network - Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 18, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>February 17, 2023</last_update_submitted>
  <last_update_submitted_qc>February 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2023</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>Dexamethasone</mesh_term>
    <mesh_term>Pomalidomide</mesh_term>
    <mesh_term>Elotuzumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03030261
org study id: 201701084
secondary id: CA204-225
secondary id: PO-CL-MM-PI-008341
nct id: NCT03030261
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Based on the need to improve outcomes post second autologous stem cell transplant (ASCT) for
      multiple myeloma (MM) and the benefits seen of maintenance treatment following initial ASCT,
      the natural next step is to evaluate maintenance/continuation therapy following second ASCT.

      Pomalidomide is active against MM cells refractory to both bortezomib and lenalidomide,
      making it an ideal choice for continuation therapy following second ASCT. Adding elotuzumab
      may increase efficacy and also the durability of responses which is essential to improving
      outcomes following second ASCT.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Event-free survival (EFS) rate
time frame: 1 year
description: -Event-free survival (EFS) will be defined as time from ASCT to disease progression, relapse, or death, whichever occurs first. Patients who are removed from study therapy prior to any of these events occurring will be censored at the time of initiation of subsequent anti-myeloma treatment.
measure: Overall response rate (ORR)
time frame: Through completion of treatment (estimated to be 102 weeks)
description: -Overall response rate (ORR) will be defined as the proportion of evaluable patients meeting the criteria for partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR).
measure: Complete response rate (CRR)
time frame: Through completion of treatment (estimated to be 102 weeks)
description: Complete response rate (CRR) will be defined as the proportion of evaluable patients meeting the criteria complete (CR) or stringent complete response (sCR)
Stringent complete response (sCR) requires all of the following:
CR as defined below
Normal free light chain ratio (0.26-1.65)
Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence
Complete response (CR) requires all of the following:
Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine
If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)
<5% plasma cells in the bone marrow
Disappearance of soft tissue plasmacytoma
Patients who do not meet the definition of CR based solely on residual monoclonal protein on serum electrophoresis and/or immunofixation, but are MRD-negative as described above, will also be considered CR.
measure: Event-free survival (EFS)
time frame: Up to 5 years post completion of treatment
description: -Event-free survival (EFS) will be defined as time from ASCT to disease progression, relapse, or death, whichever occurs first. Patients who are removed from study therapy prior to any of these events occurring will be censored at the time of initiation of subsequent anti-myeloma treatment.
measure: Progression-free survival (PFS)
time frame: Up to 5 years post completion of treatment
description: -Progression-free survival (PFS) will be defined as time from ASCT to disease progression or relapse. Any patient who expires or withdraws prior to disease progression or relapse will be censored at last follow-up. Patients who are removed from study therapy prior to progression or relapse will be censored at the time of initiation of subsequent anti-myeloma treatment.
measure: Overall survival (OS)
time frame: Up to 5 years post completion of treatment
description: -Overall survival (OS) will be defined as time from ASCT to death due to any causes. Patients who are alive at the time of data analyses will be censored on the last known alive date. Patients who are removed from study therapy prior death will be censored at the time of initiation of subsequent anti-myeloma treatment.
measure: Toxicity of regimen as measured by frequency of adverse events per the number of participants treated
time frame: Up to 30 days following completion of treatment (estimated to be 106 weeks)
description: -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
arm group label: Elotuzumab + Pomalidomide + Dexamethasone
arm group type: Experimental
description: Patients will undergo standard of care ASCT melphalan conditioning. Administration of melphalan and the second ASCT will be done as part of routine care and procedures are not dictated by this protocol.
Continuation therapy with Elo-Pom-Dex will begin between Days 80 and 120 following the second ASCT:
Elotuzumab on Days 1 and 15 for Cycles 1-6 followed by 20 mg/kg on Day 1 for Cycles 7+
Pomalidomide daily on Days 1-21 of all cycles
Dexamethasone on Days 1 and 15 of all cycles
Continuation therapy may continue until relapse or progression.
intervention type: Drug
intervention name: Elotuzumab
description: During continuation therapy, elotuzumab will be administered on a 28-day cycle as follows: on Days 1 and 15 for Cycles 1-6 and on Day 1 for Cycles 7+. For Cycles 1-6 elotuzumab will be administered intravenously at a dose of 10 mg/kg. For Cycles 7+ elotuzumab will be administered at a dose of 20 mg/kg.
arm group label: Elotuzumab + Pomalidomide + Dexamethasone
other name: Empliciti
intervention type: Drug
intervention name: Pomalidomide
description: During continuation therapy, pomalidomide will be taken by mouth daily on Days 1-21 of each 28-day cycle at a starting dose of 2 mg. During continuation, pomalidomide may be dose escalated to 4 mg at the discretion of the treating physician if the 2 mg dose is tolerated.
arm group label: Elotuzumab + Pomalidomide + Dexamethasone
other name: Pomalyst
intervention type: Drug
intervention name: Dexamethasone
description: During continuation therapy, dexamethasone will be taken by mouth at a starting dose of 40 mg. It will be given on a 28-day cycle as follows: on Days 1 and 15 for Cycles 1-6 and on Day 1 only for Cycles 7+. Sufficient quantity of drug for one cycle of therapy will be prescribed to the patient at a time.
arm group label: Elotuzumab + Pomalidomide + Dexamethasone
other name: Decadron
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ravi Vij, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
facility: 
facility: 
country: Canada
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Pomalidomide
mesh term: Elotuzumab
sharing ipd: No