<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/NCT02252263</url>
  </required_header>
  <id_info>
    <org_study_id>CA223-028</org_study_id>
    <nct_id>NCT02252263</nct_id>
  </id_info>
  <brief_title>A Phase I Open Label Study of the Safety and Tolerability of Elotuzumab (BMS-901608) Administered in Combination With Either Lirilumab (BMS-986015) or Urelumab (BMS-663513) in Subjects With Multiple Myeloma</brief_title>
  <official_title>A Phase I Open Label Dose Escalation and Randomized Cohort Expansion Study of the Safety and Tolerability of Elotuzumab (BMS-901608) Administered in Combination With Either Lirilumab (BMS-986015) or Urelumab (BMS-663513) in Subjects With Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bristol-Myers Squibb</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the safety and tolerability, characterize the dose limiting toxicities (DLTs) and&#xD;
      identify the maximally tolerated dose (MTD) of Elotuzumab administered in combination with&#xD;
      either Lirilumab or Urelumab in subjects with multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Allocation:&#xD;
&#xD;
        -  Part1: Non-randomized&#xD;
&#xD;
        -  Part2: Randomized&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 9, 2014</start_date>
  <completion_date type="Actual">October 10, 2017</completion_date>
  <primary_completion_date type="Actual">October 10, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety as measured by the rate of AEs, SAEs, deaths is the primary endpoint of this Phase 1 study. All subjects who receive at least one (full or partial) dose of Elotuzumab, Lirilumab or Urelumab will be evaluated for safety</measure>
    <time_frame>During treatment and first 100 days after treatment</time_frame>
    <description>adverse events (AEs), serious adverse events (SAEs)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response (BOR)</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response rate (ORR)</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Duration of Response (mDOR)</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Time to Response (mTTR)</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival rate (PFSR)</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>M-protein levels</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal Residual Disease (MRD) status for Post Autologous Transplant subjects</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration of Urelumab (Cmax)</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration of Lirilumab (Cmax)</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the Curve (AUCTAU) of Urelumab</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the Curve (AUCTAU) of Lirilumab</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution (Vz) for Urelumab</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Clearance (CLT) of Urelumab</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Clearance (CLT) of Lirilumab</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration at the end of infusion (ceoinf) of Urelumab</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration at the end of infusion (ceoinf) of Elotuzumab</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration at the end of infusion (ceoinf) of Lirilumab</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin will be capture at steady state of all study subjects</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurence of Specific anti-drug antibodies (ADA) to each study drug</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ADA status of the subject Biomarkers: NK and T cell numbers, Phenotypic and functional measures in cohort expansion subjects</measure>
    <time_frame>At different timepoints approximately up to 2.5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Arm 1: Elotuzumab + Lirilumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Elotuzumab weekly for 8 wks and every 2 wks thereafter + Lirilumab every 4 wks Intravenous solution for Up to 2 yrs, depending on response</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: Elotuzumab + Urelumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Elotuzumab weekly for 8 wks and every 2 wks thereafter + Urelumab every 4 wks Intravenous solution for Up to 26 weeks, depending on response</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Elotuzumab</intervention_name>
    <arm_group_label>Arm 1: Elotuzumab + Lirilumab</arm_group_label>
    <arm_group_label>Arm 2: Elotuzumab + Urelumab</arm_group_label>
    <other_name>BMS-901608</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lirilumab</intervention_name>
    <arm_group_label>Arm 1: Elotuzumab + Lirilumab</arm_group_label>
    <other_name>BMS-986015</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Urelumab</intervention_name>
    <arm_group_label>Arm 2: Elotuzumab + Urelumab</arm_group_label>
    <other_name>BMS-663513</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        For more information regarding BMS clinical trial participation, please visit&#xD;
        www.BMSStudyConnect.com&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must have histological confirmation of multiple myeloma with measurable&#xD;
             disease (per International Myeloma Working Group (IMWG) criteria):&#xD;
&#xD;
               -  Relapsed/refractory multiple myeloma, subjects who are post autologous transplant&#xD;
                  and have achieved very good partial response (VGPR) or complete response (nCR)&#xD;
                  with minimal residual disease (MRD)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bristol-Myers Squibb</last_name>
    <role>Study Director</role>
    <affiliation>Bristol-Myers Squibb</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Of Arkansas For Medical Sciences</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Sidney Kimmel Comprehensive Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://bms.com/studyconnect/Pages/home.aspx</url>
    <description>BMS Clinical Trial Patient Recruiting</description>
  </link>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>October 30, 2017</last_update_submitted>
  <last_update_submitted_qc>October 30, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Elotuzumab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02252263
org study id: CA223-028
nct id: NCT02252263
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To assess the safety and tolerability, characterize the dose limiting toxicities (DLTs) and
      identify the maximally tolerated dose (MTD) of Elotuzumab administered in combination with
      either Lirilumab or Urelumab in subjects with multiple myeloma.
Allocation:

        -  Part1: Non-randomized

        -  Part2: Randomized
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety as measured by the rate of AEs, SAEs, deaths is the primary endpoint of this Phase 1 study. All subjects who receive at least one (full or partial) dose of Elotuzumab, Lirilumab or Urelumab will be evaluated for safety
time frame: During treatment and first 100 days after treatment
description: adverse events (AEs), serious adverse events (SAEs)
measure: Best Overall Response (BOR)
time frame: At different timepoints approximately up to 2.5 years
measure: Objective Response rate (ORR)
time frame: At different timepoints approximately up to 2.5 years
measure: Median Duration of Response (mDOR)
time frame: At different timepoints approximately up to 2.5 years
measure: Median Time to Response (mTTR)
time frame: At different timepoints approximately up to 2.5 years
measure: Progression-free survival rate (PFSR)
time frame: At different timepoints approximately up to 2.5 years
measure: M-protein levels
time frame: At different timepoints approximately up to 2.5 years
measure: Minimal Residual Disease (MRD) status for Post Autologous Transplant subjects
time frame: At different timepoints approximately up to 2.5 years
measure: Maximum concentration of Urelumab (Cmax)
time frame: At different timepoints approximately up to 2.5 years
measure: Maximum concentration of Lirilumab (Cmax)
time frame: At different timepoints approximately up to 2.5 years
measure: Area under the Curve (AUCTAU) of Urelumab
time frame: At different timepoints approximately up to 2.5 years
measure: Area under the Curve (AUCTAU) of Lirilumab
time frame: At different timepoints approximately up to 2.5 years
measure: Volume of distribution (Vz) for Urelumab
time frame: At different timepoints approximately up to 2.5 years
measure: Total Clearance (CLT) of Urelumab
time frame: At different timepoints approximately up to 2.5 years
measure: Total Clearance (CLT) of Lirilumab
time frame: At different timepoints approximately up to 2.5 years
measure: Concentration at the end of infusion (ceoinf) of Urelumab
time frame: At different timepoints approximately up to 2.5 years
measure: Concentration at the end of infusion (ceoinf) of Elotuzumab
time frame: At different timepoints approximately up to 2.5 years
measure: Concentration at the end of infusion (ceoinf) of Lirilumab
time frame: At different timepoints approximately up to 2.5 years
measure: Cmin will be capture at steady state of all study subjects
time frame: At different timepoints approximately up to 2.5 years
measure: Occurence of Specific anti-drug antibodies (ADA) to each study drug
time frame: At different timepoints approximately up to 2.5 years
measure: ADA status of the subject Biomarkers: NK and T cell numbers, Phenotypic and functional measures in cohort expansion subjects
time frame: At different timepoints approximately up to 2.5 years
arm group label: Arm 1: Elotuzumab + Lirilumab
arm group type: Experimental
description: Elotuzumab weekly for 8 wks and every 2 wks thereafter + Lirilumab every 4 wks Intravenous solution for Up to 2 yrs, depending on response
arm group label: Arm 2: Elotuzumab + Urelumab
arm group type: Experimental
description: Elotuzumab weekly for 8 wks and every 2 wks thereafter + Urelumab every 4 wks Intravenous solution for Up to 26 weeks, depending on response
intervention type: Drug
intervention name: Elotuzumab
arm group label: Arm 1: Elotuzumab + Lirilumab
arm group label: Arm 2: Elotuzumab + Urelumab
other name: BMS-901608
intervention type: Drug
intervention name: Lirilumab
arm group label: Arm 1: Elotuzumab + Lirilumab
other name: BMS-986015
intervention type: Drug
intervention name: Urelumab
arm group label: Arm 2: Elotuzumab + Urelumab
other name: BMS-663513
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
country: United States
url: http://bms.com/studyconnect/Pages/home.aspx
description: BMS Clinical Trial Patient Recruiting
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Elotuzumab