<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/NCT03227432</url>
  </required_header>
  <id_info>
    <org_study_id>16-645</org_study_id>
    <nct_id>NCT03227432</nct_id>
  </id_info>
  <brief_title>An Exploratory Study to Evaluate the Combination of Elotuzumab and Nivolumab With and Without Pomalidomide in Relapsed Refractory Multiple Myeloma</brief_title>
  <official_title>An Exploratory Study to Evaluate the Combination of Elotuzumab and Nivolumab With and Without Pomalidomide in Relapsed Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is studying a combination of targeted therapies as a possible treatment&#xD;
      for multiple myeloma (MM).&#xD;
&#xD;
      The drugs involved in this study are:&#xD;
&#xD;
        -  Elotuzumab&#xD;
&#xD;
        -  Nivolumab&#xD;
&#xD;
        -  Pomalidomide&#xD;
&#xD;
        -  Dexamethasone&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Phase II clinical trial. Phase II clinical trials test the safety&#xD;
      and effectiveness of an investigational drug combination to learn whether the combination&#xD;
      works in treating a specific disease. &quot;Investigational&quot; means that the drug combination is&#xD;
      being studied.&#xD;
&#xD;
      This study has two parts. Each part tests a different combination of drugs.&#xD;
&#xD;
        -  In Part 1 participants will be given elotuzumab and nivolumab.&#xD;
&#xD;
        -  In Part 2 participants will be given elotuzumab, nivolumab, pomalidomide, and&#xD;
           dexamethasone.&#xD;
&#xD;
      Each of these drugs works in a different way to help the body fight multiple myeloma. The&#xD;
      drugs are being tested in different combinations to see if they are more effective when taken&#xD;
      together.&#xD;
&#xD;
      Elotuzumab is an antibody, that stimulates the immune system to fight your disease. The FDA&#xD;
      (the U.S. Food and Drug Administration) has approved elotuzumab in combination with&#xD;
      lenalidomide as a treatment option for this disease.&#xD;
&#xD;
      In this research study, the participant will receive pomalidomide which is an&#xD;
      immunomodulatory drug. This means that pomalidomide modulates the immune system to help fight&#xD;
      the disease. The FDA has approved pomalidomide as a treatment option for this disease after&#xD;
      receiving two other therapies.&#xD;
&#xD;
      Dexamethasone, also FDA approved, is a type of steroid and is usually combined with other&#xD;
      chemotherapy for the treatment of blood cancers, such as myeloma and leukemias.&#xD;
&#xD;
      The FDA has not approved nivolumab for this specific disease but it has been approved for&#xD;
      other uses, specifically lung cancer. Nivolumab works by blocking an inhibitory signal within&#xD;
      immune cells, potentially allowing the immune system to fight the cancer.&#xD;
&#xD;
      In this research study the investigators are looking to see if the combination of elotuzumab,&#xD;
      nivolumab, pomalidomide, and dexamethasone is effective in fighting the cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Withdrawn before enrollment due to issues around the FDA hold on PD-1/PD-L1 drugs in&#xD;
    combination with IMIDs.&#xD;
  </why_stopped>
  <start_date type="Anticipated">December 2018</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response Rate</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Rate of Clinical Benefit Response (CBR)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Treatment Failure</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Nivolumab + Elotuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>22 patients will be entered, If &gt; 4 patients achieve at least a partial response (PR) within 4 cycles an additional 18 patients will be treated.&#xD;
Nivolumab will be administered intravenously twice per cycle for cycle 1-4&#xD;
Nivolumab will be administered intravenously once per cycle for cycle 5&#xD;
Elotuzumab will be administered intravenously 4 times per cycle for cycle 1-2&#xD;
Elotuzumab will be administered intravenously twice per cycle for cycle 3-4&#xD;
Elotuzumab will be administered intravenously once per cycle for cycle 5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nivolumab will be administered intravenously twice per cycle for cycle 1-4&#xD;
Nivolumab will be administered intravenously once per cycle for cycle 5&#xD;
Elotuzumab will be administered intravenously 4 times per cycle for cycle 1-2&#xD;
Elotuzumab will be administered intravenously twice per cycle for cycle 3-4&#xD;
Elotuzumab will be administered intravenously once per cycle for cycle 5&#xD;
Pomalidomide will be administered for 21 days per cycle&#xD;
Dexamethasone will be administered weekly</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone, a corticosteroid, is similar to a natural hormone produced by adrenal glands. It relieves inflammation.</description>
    <arm_group_label>Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone</arm_group_label>
    <other_name>Maxidex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pomalidomide</intervention_name>
    <description>Pomalidomide which is an immunomodulatory drug. This means that pomalidomide modulates the immune system to help fight diseases.</description>
    <arm_group_label>Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone</arm_group_label>
    <other_name>Pomalyst</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Elotuzumab</intervention_name>
    <description>Elotuzumab is an antibody, that stimulates the immune system to fight diseases</description>
    <arm_group_label>Nivolumab + Elotuzumab</arm_group_label>
    <arm_group_label>Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone</arm_group_label>
    <other_name>Empliciti</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab works by blocking an inhibitory signal within immune cells, potentially allowing the immune system to fight the cancer</description>
    <arm_group_label>Nivolumab + Elotuzumab</arm_group_label>
    <arm_group_label>Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone</arm_group_label>
    <other_name>Opdivo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patient ≥ age 18 years&#xD;
&#xD;
          -  Patient is able to understand and has given voluntary written informed consent before&#xD;
             performance of any study-related procedures not part of normal medical care, with the&#xD;
             understanding that consent may be withdrawn by the patient at any time without&#xD;
             prejudice to their future medical care&#xD;
&#xD;
          -  Patient has been previously diagnosed with MM based on standard International Myeloma&#xD;
             Working Group (IMWG) criteria and currently requires treatment.&#xD;
&#xD;
          -  Patient must have received at least two previous lines of therapy for multiple myeloma&#xD;
             including lenalidomide or thalidomide and a proteasome inhibitor (bortezomib,&#xD;
             carfilzomib or ixazomib).&#xD;
&#xD;
          -  Patient must have demonstrated disease progression on or within 60 days of completion&#xD;
             of the last therapy. Patient has measurable disease defined as at least one of the&#xD;
             following:&#xD;
&#xD;
               -  Serum M protein ≥ 0.5 g/dL (≥5 g/L)&#xD;
&#xD;
               -  Urine M protein ≥200 mg/24 hours&#xD;
&#xD;
               -  Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and&#xD;
                  an abnormal serum FLC ratio (&lt;0.26 or &gt;1.65)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Appendix A)&#xD;
&#xD;
          -  Negative serum or urine pregnancy test for women of child-bearing potential&#xD;
&#xD;
          -  Screening Laboratory parameters:&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L). Granulocyte&#xD;
             colony-stimulating factor (GCSF) is not permitted during screening to meet eligibility&#xD;
             criteria and within 14 days of initiation of therapy&#xD;
&#xD;
               -  Platelet count ≥ 75,000 cells/dL (75 x 109/L) Platelet transfusion is not&#xD;
                  permitted during screening to meet eligibility criteria and within 14 days of&#xD;
                  initiation of therapy&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g/dl ( red blood cell (RBC) transfusions are permitted during&#xD;
                  the screening period)&#xD;
&#xD;
               -  Total Bilirubin ≤ 1.5 X upper limit of normal (ULN) (Patients with known Gilbert&#xD;
                  Syndrome are allowed to have total bilirubin &lt; 3.0 mg/dL)&#xD;
&#xD;
               -  Aspartate transaminase (AST, or SGOT) and alanine transaminase (ALT, or SGPT) ≤&#xD;
                  3.0x ULN&#xD;
&#xD;
               -  Estimated creatinine clearance by Cockcroft-Gault formula ≥ 40 mL/min&#xD;
&#xD;
               -  Serum creatinine &lt; 1.5 X ULN. (Appendix C)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosed or treated for another malignancy within 3 years prior to enrollment, with&#xD;
             the exception of complete resection of basal cell carcinoma or squamous cell carcinoma&#xD;
             of the skin, an in situ malignancy, or low risk prostate cancer after curative&#xD;
             therapy.&#xD;
&#xD;
          -  Prior therapy with pomalidomide&#xD;
&#xD;
          -  Prior treatment with monoclonal antibodies including elotuzumab&#xD;
&#xD;
          -  Prior therapy with anti-programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1)&#xD;
             agents.&#xD;
&#xD;
          -  Received any investigational drug within 14 days or 5 half-lives of the&#xD;
             investigational drug, whichever is longer.&#xD;
&#xD;
          -  Prior anti-cancer therapy within 14 days.&#xD;
&#xD;
          -  Patient has any Grade 3 or &gt; unresolved adverse reaction from previous treatment.&#xD;
             Previous allogeneic stem cell transplantation with active graft-versus-host disease&#xD;
             (GVHD) or being under immunosuppressive therapy in the last 2 months prior to&#xD;
             inclusion in the trial.&#xD;
&#xD;
          -  Autologous stem cell transplant if &lt; 12 weeks from enrollment.&#xD;
&#xD;
          -  Daily requirement for oral corticosteroids (equivalent to &gt; 10 mg/day prednisone&#xD;
             daily) Inhaled or topical corticosteroids are allowed.&#xD;
&#xD;
          -  Patient is human immunodeficiency virus (HIV) positive,.&#xD;
&#xD;
          -  Patient is Hepatitis B Surface antigen-positive.&#xD;
&#xD;
          -  Patient has active hepatitis C infection.&#xD;
&#xD;
          -  Patient has an autoimmune disease. (Subjects are permitted to enroll if they have&#xD;
             vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune&#xD;
             condition only requiring hormone replacement, psoriasis not requiring systemic&#xD;
             treatment, or conditions not expected to recur in the absence of an external trigger).&#xD;
&#xD;
          -  Any clinically significant, uncontrolled medical conditions that, in the treating&#xD;
             Investigator's opinion, would impose excessive risk to the patient or may interfere&#xD;
             with compliance or interpretation of the study results. Uncontrolled intercurrent&#xD;
             illness may include, but is not limited to, ongoing or active infection, symptomatic&#xD;
             congestive heart failure, unstable angina pectoris, clinically significant cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations as determined by treating&#xD;
             investigator that would limit compliance with study requirements.&#xD;
&#xD;
          -  History of erythema multiforme or severe hypersensitivity to prior IMiD's®&#xD;
&#xD;
          -  Inability to tolerate thromboprophylaxis&#xD;
&#xD;
          -  Known severe intolerance to prior steroid therapy (Grade 3 or above adverse event&#xD;
             which was unresponsive to a dose reduction)&#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>Jacob Laubach, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>July 7, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>August 10, 2018</last_update_submitted>
  <last_update_submitted_qc>August 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Jacob Laubach</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Multiple Myeloma</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>Dexamethasone</mesh_term>
    <mesh_term>Nivolumab</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/NCT03227432
org study id: 16-645
nct id: NCT03227432
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research study is studying a combination of targeted therapies as a possible treatment
      for multiple myeloma (MM).

      The drugs involved in this study are:

        -  Elotuzumab

        -  Nivolumab

        -  Pomalidomide

        -  Dexamethasone
This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug combination to learn whether the combination
      works in treating a specific disease. "Investigational" means that the drug combination is
      being studied.

      This study has two parts. Each part tests a different combination of drugs.

        -  In Part 1 participants will be given elotuzumab and nivolumab.

        -  In Part 2 participants will be given elotuzumab, nivolumab, pomalidomide, and
           dexamethasone.

      Each of these drugs works in a different way to help the body fight multiple myeloma. The
      drugs are being tested in different combinations to see if they are more effective when taken
      together.

      Elotuzumab is an antibody, that stimulates the immune system to fight your disease. The FDA
      (the U.S. Food and Drug Administration) has approved elotuzumab in combination with
      lenalidomide as a treatment option for this disease.

      In this research study, the participant will receive pomalidomide which is an
      immunomodulatory drug. This means that pomalidomide modulates the immune system to help fight
      the disease. The FDA has approved pomalidomide as a treatment option for this disease after
      receiving two other therapies.

      Dexamethasone, also FDA approved, is a type of steroid and is usually combined with other
      chemotherapy for the treatment of blood cancers, such as myeloma and leukemias.

      The FDA has not approved nivolumab for this specific disease but it has been approved for
      other uses, specifically lung cancer. Nivolumab works by blocking an inhibitory signal within
      immune cells, potentially allowing the immune system to fight the cancer.

      In this research study the investigators are looking to see if the combination of elotuzumab,
      nivolumab, pomalidomide, and dexamethasone is effective in fighting the cancer.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response Rate
time frame: 2 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 6 months
measure: The Rate of Clinical Benefit Response (CBR)
time frame: 2 years
measure: Time to Response
time frame: 2 years
measure: Duration of Response
time frame: 2 years
measure: Progression Free Survival
time frame: 2 years
measure: Overall Survival
time frame: 2 years
measure: Time to Treatment Failure
time frame: 2 years
arm group label: Nivolumab + Elotuzumab
arm group type: Experimental
description: 22 patients will be entered, If > 4 patients achieve at least a partial response (PR) within 4 cycles an additional 18 patients will be treated.
Nivolumab will be administered intravenously twice per cycle for cycle 1-4
Nivolumab will be administered intravenously once per cycle for cycle 5
Elotuzumab will be administered intravenously 4 times per cycle for cycle 1-2
Elotuzumab will be administered intravenously twice per cycle for cycle 3-4
Elotuzumab will be administered intravenously once per cycle for cycle 5
arm group label: Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone
arm group type: Experimental
description: Nivolumab will be administered intravenously twice per cycle for cycle 1-4
Nivolumab will be administered intravenously once per cycle for cycle 5
Elotuzumab will be administered intravenously 4 times per cycle for cycle 1-2
Elotuzumab will be administered intravenously twice per cycle for cycle 3-4
Elotuzumab will be administered intravenously once per cycle for cycle 5
Pomalidomide will be administered for 21 days per cycle
Dexamethasone will be administered weekly
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone, a corticosteroid, is similar to a natural hormone produced by adrenal glands. It relieves inflammation.
arm group label: Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone
other name: Maxidex
intervention type: Drug
intervention name: Pomalidomide
description: Pomalidomide which is an immunomodulatory drug. This means that pomalidomide modulates the immune system to help fight diseases.
arm group label: Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone
other name: Pomalyst
intervention type: Drug
intervention name: Elotuzumab
description: Elotuzumab is an antibody, that stimulates the immune system to fight diseases
arm group label: Nivolumab + Elotuzumab
arm group label: Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone
other name: Empliciti
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab works by blocking an inhibitory signal within immune cells, potentially allowing the immune system to fight the cancer
arm group label: Nivolumab + Elotuzumab
arm group label: Nivolumab+Elotuzumab+Pomalidomide+Dexamethasone
other name: Opdivo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jacob Laubach, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Jacob Laubach
investigator title: Principal Investigator
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Nivolumab
mesh term: Pomalidomide
mesh term: Elotuzumab
sharing ipd: No