<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/NCT03003728</url>
  </required_header>
  <id_info>
    <org_study_id>205009</org_study_id>
    <nct_id>NCT03003728</nct_id>
  </id_info>
  <brief_title>2015-10: Expanded Natural Killer Cells and Elotuzumab for High-Risk Myeloma Post- Autologous Stem Cell Transplant (ASCT)</brief_title>
  <official_title>2015-10: A Phase II Pilot Study of Expanded Natural Killer Cells and Elotuzumab to Eradicate High-Risk Myeloma Post Autologous Stem Cell Transplant</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Arkansas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Altor BioScience</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Arkansas</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>
      This study will evaluate the ability of Expanded Natural Killer (ENK) cells to treat multiple&#xD;
      myeloma when administered as part of a regimen consisting of Elotuzumab and a stem cell&#xD;
      transplant. Natural killer cells are a special type of white blood cells that are already&#xD;
      present in the body which have the ability to kill myeloma cells. In this study, natural&#xD;
      killer cells will be collected and then treated in a laboratory to activate and 'expand' the&#xD;
      number of cells to increase the dose and the anti-myeloma activity of the cells before they&#xD;
      are transfused back into the subject. Elotuzumab is a protein drug approved by the United&#xD;
      States Food and Drug Administration (FDA) for patients with previously treated multiple&#xD;
      myeloma and works by activating natural killer cells already present in the body and&#xD;
      targeting a protein called SLAMF7 which is present on both natural killer cells and myeloma&#xD;
      cells. The investigators hope that administering Elotuzumab in combination with ENK cells&#xD;
      will enhance the anti-myeloma activity of the ENK cells.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Withdrawal of study support&#xD;
  </why_stopped>
  <start_date type="Actual">November 1, 2019</start_date>
  <completion_date type="Actual">July 8, 2020</completion_date>
  <primary_completion_date type="Actual">July 8, 2020</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>Multiple Myeloma Response</measure>
    <time_frame>98 days post-ENK infusion (100 days post-ASCT)</time_frame>
    <description>Response will be measured according to International Myeloma Working Group (IMWG) Criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>within 98 days post-ENK infusion (100 days post-ASCT)</time_frame>
    <description>Frequency and severity of treatment-related adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persistence of ENK cells by flow cytometry and/or cytometry by time of flight (CyTOF)</measure>
    <time_frame>within 98 days post-ENK infusion (100 days post-ASCT)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Study Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Elotuzumab 10 mg/kg via intravenous infusion on days -16, -3, 12, and 26; Melphalan 200 mg/m2 Ivia intravenous infusion on day -3; ASCT on day -2; ENK infusion on day 0; ALT-803 (Interleukin-15 superagonist) 10 ug/kg via subcutaneous injection on days 1, 8, 15, and 22.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Elotuzumab</intervention_name>
    <description>Elotuzumab 10 mg/kg via intravenous infusion on days -16, -3, 12, and 26</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Empliciti</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Melphalan 200 mg/m2 Ivia intravenous infusion on day -3</description>
    <arm_group_label>Study Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Autologous Stem Cell Transplant (ASCT)</intervention_name>
    <description>ASCT on day -2</description>
    <arm_group_label>Study Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Expanded Natural Killer (ENK) Cells</intervention_name>
    <description>ENK cell infusion on day 0</description>
    <arm_group_label>Study Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ALT-803</intervention_name>
    <description>ALT-803 (Interleukin-15 superagonist) 10 ug/kg via subcutaneous injection on days 1, 8, 15, and 22</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>IL-15 superagonist</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Multiple myeloma patients that have completed induction chemotherapy and peripheral&#xD;
             blood stem cell collection (PBSC) in preparation for ASCT.&#xD;
&#xD;
          -  Patients must have high-risk disease as defined by Gene Expression Profiling (GEP) 70&#xD;
             risk score of ≥ 0.66 or GEP 80 gene score of ≥ 2.48 or metaphase cytogenetic&#xD;
             abnormalities or lactate dehydrogenase (LDH) ≥ 360 U/L (Rule out hemolysis, infection&#xD;
             and contact PI for clarification if any doubt).&#xD;
&#xD;
          -  Patients must have failed prior treatment for their multiple myeloma (MM) including a&#xD;
             proteasome inhibitor and immunomodulatory drug (so-called 'double refractory').&#xD;
             Patients who have received prior salvage combination chemotherapy after failure of&#xD;
             proteasome inhibitor and immunomodulatory drug are eligible (frank relapse at the time&#xD;
             of enrollment is not required)&#xD;
&#xD;
          -  Zubrod ≤ 2, unless solely due to symptoms of MM-related (bone) disease.&#xD;
&#xD;
          -  Patients must have a platelet count of ≥ 20,000/μL within 30 days of enrollment,&#xD;
             unless lower levels are explained by extensive bone marrow plasmacytosis or extensive&#xD;
             prior therapy.&#xD;
&#xD;
          -  Patients must be at least 18 years of age and not older than 75 years of age at the&#xD;
             time of registration.&#xD;
&#xD;
          -  must have preserved renal function as defined by a serum creatinine level of ≤ 3 mg/dL&#xD;
             within 30 days of registration.&#xD;
&#xD;
          -  Participants must have an ejection fraction by echocardiogram (ECHO) or multi-gated&#xD;
             acquisition (MUGA) scan ≥ 40% within 90 days prior to registration.&#xD;
&#xD;
          -  Patients must have adequate pulmonary function studies ≥ 50% of predicted on&#xD;
             mechanical aspects and diffusion capacity (DLCO) ≥ 50% of predicted within 90 days&#xD;
             prior to registration. If the patient is unable to complete pulmonary function tests&#xD;
             due to MM-related pain or condition, exception may be granted if the principal&#xD;
             investigator documents that the patient is a candidate for high-dose therapy.&#xD;
&#xD;
          -  Patients must have at least 2x106 CD34+ cells/kg stored for transplant. In addition,&#xD;
             there will be a 'back-up' available of 2x106 CD34+ cells/kg2x106 CD34+ cells/kg&#xD;
&#xD;
          -  Patients must have signed an Institutional Review Board-approved informed consent and&#xD;
             HIPAA authorization form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior allo-transplant.&#xD;
&#xD;
          -  Prior auto-transplantation is permitted provided the patient is still presently a&#xD;
             transplant candidate and at least 2 months should have passed since last&#xD;
             auto-transplant&#xD;
&#xD;
          -  History of poorly-controlled hypertension, diabetes mellitus, or any other serious&#xD;
             medical illness or psychiatric illness that could potentially interfere with the&#xD;
             completion of treatment according to this protocol or could be considered to be an&#xD;
             exclusion criterion deemed by the PI.&#xD;
&#xD;
          -  Patients must not have prior malignancy, except for adequately-treated basal cell or&#xD;
             squamous cell skin cancer, in situ cervical cancer, or other cancer for which the&#xD;
             patient has not received treatment for one year prior to enrollment. Other cancers&#xD;
             will only be acceptable if the patient's life expectancy exceeds three years as&#xD;
             determined by the PI.&#xD;
&#xD;
          -  Pregnant or nursing women may not participate. Women of childbearing potential must&#xD;
             have a negative pregnancy test documented within one week of registration. Women/men&#xD;
             of reproductive potential may not participate unless they have agreed to use an&#xD;
             effective contraceptive method.&#xD;
&#xD;
          -  The subject may not be positive for HIV I/II or HTLV-I/II.&#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>Frits van Rhee, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Arkansas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Arkansas for Medical Sciences</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <last_update_submitted>July 8, 2020</last_update_submitted>
  <last_update_submitted_qc>July 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2020</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>Melphalan</mesh_term>
    <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/NCT03003728
org study id: 205009
nct id: NCT03003728
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the ability of Expanded Natural Killer (ENK) cells to treat multiple
      myeloma when administered as part of a regimen consisting of Elotuzumab and a stem cell
      transplant. Natural killer cells are a special type of white blood cells that are already
      present in the body which have the ability to kill myeloma cells. In this study, natural
      killer cells will be collected and then treated in a laboratory to activate and 'expand' the
      number of cells to increase the dose and the anti-myeloma activity of the cells before they
      are transfused back into the subject. Elotuzumab is a protein drug approved by the United
      States Food and Drug Administration (FDA) for patients with previously treated multiple
      myeloma and works by activating natural killer cells already present in the body and
      targeting a protein called SLAMF7 which is present on both natural killer cells and myeloma
      cells. The investigators hope that administering Elotuzumab in combination with ENK cells
      will enhance the anti-myeloma activity of the ENK cells.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Multiple Myeloma Response
time frame: 98 days post-ENK infusion (100 days post-ASCT)
description: Response will be measured according to International Myeloma Working Group (IMWG) Criteria
measure: Adverse Events
time frame: within 98 days post-ENK infusion (100 days post-ASCT)
description: Frequency and severity of treatment-related adverse events
measure: Persistence of ENK cells by flow cytometry and/or cytometry by time of flight (CyTOF)
time frame: within 98 days post-ENK infusion (100 days post-ASCT)
arm group label: Study Treatment
arm group type: Experimental
description: Elotuzumab 10 mg/kg via intravenous infusion on days -16, -3, 12, and 26; Melphalan 200 mg/m2 Ivia intravenous infusion on day -3; ASCT on day -2; ENK infusion on day 0; ALT-803 (Interleukin-15 superagonist) 10 ug/kg via subcutaneous injection on days 1, 8, 15, and 22.
intervention type: Drug
intervention name: Elotuzumab
description: Elotuzumab 10 mg/kg via intravenous infusion on days -16, -3, 12, and 26
arm group label: Study Treatment
other name: Empliciti
intervention type: Drug
intervention name: Melphalan
description: Melphalan 200 mg/m2 Ivia intravenous infusion on day -3
arm group label: Study Treatment
intervention type: Procedure
intervention name: Autologous Stem Cell Transplant (ASCT)
description: ASCT on day -2
arm group label: Study Treatment
intervention type: Biological
intervention name: Expanded Natural Killer (ENK) Cells
description: ENK cell infusion on day 0
arm group label: Study Treatment
intervention type: Drug
intervention name: ALT-803
description: ALT-803 (Interleukin-15 superagonist) 10 ug/kg via subcutaneous injection on days 1, 8, 15, and 22
arm group label: Study Treatment
other name: IL-15 superagonist
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Frits van Rhee, MD, PhD
role: Principal Investigator
affiliation: University of Arkansas
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Melphalan
mesh term: Elotuzumab