<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/NCT03782064</url>
  </required_header>
  <id_info>
    <org_study_id>18-280</org_study_id>
    <nct_id>NCT03782064</nct_id>
  </id_info>
  <brief_title>Dendritic Cell (DC)/Myeloma Fusions in Combination With Nivolumab in Patients With Relapsed Multiple Myeloma</brief_title>
  <official_title>A Phase II Trial of Vaccination With Dendritic Cell (DC)/Myeloma Fusions in Combination With Nivolumab in Patients With Relapsed Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beth Israel Deaconess Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Beth Israel Deaconess Medical Center</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 cancer vaccine called Dendritic Cell/MM Fusion vaccine&#xD;
      (DC/MM vaccine) in combination with nivolumab, as a possible treatment for multiple myeloma&#xD;
      (MM).&#xD;
&#xD;
      The drugs involved in this study are:&#xD;
&#xD;
        -  Dendritic Cell/MM Fusion vaccine (DC/MM vaccine)&#xD;
&#xD;
        -  Nivolumab, an immunotherapy drug&#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 to learn whether the drug works in treating a&#xD;
      specific disease. &quot;Investigational&quot; means that the drug is being studied.&#xD;
&#xD;
      The FDA (the U.S. Food and Drug Administration) has not approved the DC/MM vaccine as a&#xD;
      treatment for any disease.&#xD;
&#xD;
      The FDA has not approved nivolumab for multiple myeloma. A similar immunotherapy drug used in&#xD;
      combination with IMiDs (drugs that regulate or modify the immune system) was associated with&#xD;
      higher risk of death in another research trial in patients with multiple myeloma; however,&#xD;
      nivolumab has been approved for use in several other types of cancers.&#xD;
&#xD;
      The FDA has not approved the combination of nivolumab with the DC/MM vaccine as a treatment&#xD;
      for any disease.&#xD;
&#xD;
      In this research study, the investigators wish to determine whether nivolumab administered in&#xD;
      combination with the DC/MM vaccine will help promote an immune response against multiple&#xD;
      myeloma cells.&#xD;
&#xD;
      An immune response is any reaction by the immune system. It helps the body distinguish itself&#xD;
      from substances foreign to it, such as infections and dangerous substances. Cancer cells have&#xD;
      unique markers that distinguish them from normal cells, which can potentially serve as&#xD;
      targets for the immune system.&#xD;
&#xD;
      The DC/MM vaccine is an investigational agent that tries to help the immune system recognize&#xD;
      and fight against cancer cells, utilizing those unique markers. Unlike a standard vaccine&#xD;
      that is used to prevent infections, cancer vaccines are being studied to see if they can&#xD;
      fight cancers that are already in the body. Laboratory studies suggest that when dendritic&#xD;
      cells (a type of immune cell that helps to tell your immune system what is good and what is&#xD;
      bad) and tumor cells are brought together, the dendritic cells can stimulate immune responses&#xD;
      against the tumor.&#xD;
&#xD;
      Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a&#xD;
      type of protein that protects the body against foreign invaders, called antigens, by grabbing&#xD;
      hold of antigens to stop them from invading your system. Monoclonal indicated that this&#xD;
      antibody was made in a lab. Nivolumab has been shown to react against cancer cells, including&#xD;
      MM cells. The investigators hope that the addition of nivolumab with the DC/MM vaccine will&#xD;
      help the body fight MM&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Funding&#xD;
  </why_stopped>
  <start_date type="Actual">February 22, 2019</start_date>
  <completion_date type="Actual">January 31, 2021</completion_date>
  <primary_completion_date type="Actual">January 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>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>Number of Patients Who Develop Immunologic Response to Nivolumab and the DC/MM Fusion Vaccine</measure>
    <time_frame>2 years</time_frame>
    <description>We planned to evaluate the immunologic response to treatment in blood and bone marrow. Two patients were treated on protocol and both came off due to disease progression early in the course of therapy (one patient during cycle 1 and one patient during cycle 3.) As such, there is insufficient data to perform what had been planned in correlative science studies so no samples were analyzed. This study has been stopped and no further patients are being enrolled and no further samples are being collected. No data has been obtained for any immune analysis; therefore no immune or clinical data will be reported on this trial.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Who Achieve a Clinical Response (SD, PR, VGPR, CR)</measure>
    <time_frame>2 years</time_frame>
    <description>We looked at the two patients who were treated and evaluated their response to treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0</measure>
    <time_frame>2 years</time_frame>
    <description>We evaluated the number of patients who developed a related adverse event as assessed by the CTCAE version 4.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Who Are Alive Without Progression at 2 Years</measure>
    <time_frame>2 years</time_frame>
    <description>We calculated the number of patients who were alive without progression at 2 years</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Nivolumab+DC/myeloma fusions/GM-CSF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nivolumab will be given every two weeks&#xD;
The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects your body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Nivolumab has been shown to react against cancer cells, including MM cells.</description>
    <arm_group_label>Nivolumab+DC/myeloma fusions/GM-CSF</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DC/myeloma fusions/GM-CSF</intervention_name>
    <description>The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing unique markers.</description>
    <arm_group_label>Nivolumab+DC/myeloma fusions/GM-CSF</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have Patients with relapsed multiple myeloma with prior treatment of an&#xD;
             IMID and proteasome inhibitor.&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  ECOG performance status ≤2&#xD;
&#xD;
          -  Patients must have &gt; 20% plasma cells in the bone marrow aspirate differential &lt;30&#xD;
             days prior to enrollment.&#xD;
&#xD;
          -  ANC &gt; 1000; Platelets &gt; 75K without transfusional support&#xD;
&#xD;
          -  Participants must have normal organ function as defined below:&#xD;
&#xD;
               -  total bilirubin ≤1.5 × institutional upper limit of normal&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal&#xD;
&#xD;
               -  creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels&#xD;
                  above institutional normal.&#xD;
&#xD;
          -  The effects of DC/MM fusion and nivolumab on the developing human fetus are unknown.&#xD;
             For this reason, women of child-bearing potential and men must agree to use adequate&#xD;
             contraception (hormonal or barrier method of birth control; abstinence) prior to study&#xD;
             entry and for the duration of study participation. Should a woman become pregnant or&#xD;
             suspect she is pregnant while she or her partner is participating in this study, she&#xD;
             should inform her treating physician immediately. Men treated or enrolled on this&#xD;
             protocol must also agree to use adequate contraception prior to the study, for the&#xD;
             duration of study participation, and 5 months after completion of treatment.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -Participants who are receiving any other investigational agents.&#xD;
&#xD;
        3.2.2 Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in&#xD;
        serum as measured by electrophoresis and immunofixation and the absence of Bence-Jones&#xD;
        protein in the urine defined by use of conventional electrophoresis and immunofixation&#xD;
        techniques and the absence of involved serum free light chain &gt;100 mg/L]. Patients with&#xD;
        light chain MM detected in the serum by free light chain assay are eligible.&#xD;
&#xD;
          -  Patients with Plasma Cell Leukemia&#xD;
&#xD;
          -  Because of compromised cellular immunity, patients who have a known human&#xD;
             immunodeficiency virus (HIV), active hepatitis C virus (HCV) or active hepatitis B&#xD;
             virus (HBV).&#xD;
&#xD;
          -  Myocardial infarction within 6 months prior to enrollment or New York Heart&#xD;
             Association (NYHA) Class III or IV heart failure (see Appendix H), uncontrolled&#xD;
             angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence&#xD;
             of acute ischemia or active conduction system abnormalities. Prior to study entry, any&#xD;
             ECG abnormality at screening will be documented by the investigator as not medically&#xD;
             relevant.&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders including but not&#xD;
             limited to the following:&#xD;
&#xD;
               -  GI Disorders: (including inflammatory bowel disease [e.g. ulcerative colitis,&#xD;
                  Crohn's disease], diverticulitis (with the exception of a prior episode that has&#xD;
                  resolved), celiac disease, or other serious gastrointestinal chronic conditions&#xD;
                  associated with diarrhea.&#xD;
&#xD;
               -  Systemic lupus erythematosus&#xD;
&#xD;
          -  Wegener's syndrome [granulomatosis with polyangiitis]&#xD;
&#xD;
               -  Myasthenia gravis&#xD;
&#xD;
               -  Graves' disease&#xD;
&#xD;
               -  Rheumatoid arthritis&#xD;
&#xD;
               -  Hypophysitis&#xD;
&#xD;
               -  Uveitis&#xD;
&#xD;
          -  The following are exceptions to this criterion: subjects with vitiligo or alopecia;&#xD;
             subjects with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone&#xD;
             replacement; or subjects with psoriasis not requiring systemic treatment.&#xD;
&#xD;
          -  Individuals with a history of a different malignancy are ineligible except for the&#xD;
             following circumstances. Note: Individuals with a history of other malignancies are&#xD;
             eligible if they have been disease-free for at least 5 years and are deemed by the&#xD;
             investigator to be at low risk for recurrence of that malignancy. Individuals with the&#xD;
             following cancers are eligible if diagnosed and treated within the past 5 years:&#xD;
             non-invasive cancer (such as, any in situ cancers) and basal cell or squamous cell&#xD;
             carcinoma of the skin.&#xD;
&#xD;
          -  Female patients who are pregnant (positive β-HCG) or breastfeeding&#xD;
&#xD;
          -  Prior organ transplant requiring immunosuppressive therapy.&#xD;
&#xD;
          -  Patients who previously received PD-1 antibody and have experienced toxicities&#xD;
             resulting in treatment discontinuation.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#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>Jacalyn Rosenblatt, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beth Israel Deaconess Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <results_first_submitted>March 14, 2022</results_first_submitted>
  <results_first_submitted_qc>August 10, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 1, 2022</results_first_posted>
  <last_update_submitted>June 16, 2023</last_update_submitted>
  <last_update_submitted_qc>June 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beth Israel Deaconess Medical Center</investigator_affiliation>
    <investigator_full_name>Jacalyn Rosenblatt</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>Nivolumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor-Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data can be shared no earlier than 1 year following the date of publication</ipd_time_frame>
    <ipd_access_criteria>Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu</ipd_access_criteria>
  </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>October 17, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT03782064/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Nivolumab+DC/Myeloma Fusions/GM-CSF</title>
          <description>Nivolumab will be given every two weeks&#xD;
The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle&#xD;
Nivolumab: Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects your body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Nivolumab has been shown to react against cancer cells, including MM cells.&#xD;
DC/myeloma fusions/GM-CSF: The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing unique markers.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Initiated Treatment</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </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="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progression Prior to Starting Treatment</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participants who Initiated Treatment</population>
      <group_list>
        <group group_id="B1">
          <title>Nivolumab+DC/Myeloma Fusions/GM-CSF</title>
          <description>Nivolumab will be given every two weeks&#xD;
The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle&#xD;
Nivolumab: Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects your body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Nivolumab has been shown to react against cancer cells, including MM cells.&#xD;
DC/myeloma fusions/GM-CSF: The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing unique markers.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
          </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="0"/>
                  </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>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75" lower_limit="74" upper_limit="76"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</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="0"/>
                  </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="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients Who Develop Immunologic Response to Nivolumab and the DC/MM Fusion Vaccine</title>
        <description>We planned to evaluate the immunologic response to treatment in blood and bone marrow. Two patients were treated on protocol and both came off due to disease progression early in the course of therapy (one patient during cycle 1 and one patient during cycle 3.) As such, there is insufficient data to perform what had been planned in correlative science studies so no samples were analyzed. This study has been stopped and no further patients are being enrolled and no further samples are being collected. No data has been obtained for any immune analysis; therefore no immune or clinical data will be reported on this trial.</description>
        <time_frame>2 years</time_frame>
        <population>Two patients were treated on protocol and both came off due to disease progression early in the course of therapy. Both participants did not achieve a defined clinical response. There is insufficient data to perform what had been planned in correlative science studies or in immune analysis. This study has been stopped and no further patients are being enrolled and no further samples are being collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab+DC/Myeloma Fusions/GM-CSF</title>
            <description>Nivolumab will be given every two weeks&#xD;
The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle&#xD;
Nivolumab: Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects your body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Nivolumab has been shown to react against cancer cells, including MM cells.&#xD;
DC/myeloma fusions/GM-CSF: The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing unique markers.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Develop Immunologic Response to Nivolumab and the DC/MM Fusion Vaccine</title>
          <description>We planned to evaluate the immunologic response to treatment in blood and bone marrow. Two patients were treated on protocol and both came off due to disease progression early in the course of therapy (one patient during cycle 1 and one patient during cycle 3.) As such, there is insufficient data to perform what had been planned in correlative science studies so no samples were analyzed. This study has been stopped and no further patients are being enrolled and no further samples are being collected. No data has been obtained for any immune analysis; therefore no immune or clinical data will be reported on this trial.</description>
          <population>Two patients were treated on protocol and both came off due to disease progression early in the course of therapy. Both participants did not achieve a defined clinical response. There is insufficient data to perform what had been planned in correlative science studies or in immune analysis. This study has been stopped and no further patients are being enrolled and no further samples are being collected.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Who Achieve a Clinical Response (SD, PR, VGPR, CR)</title>
        <description>We looked at the two patients who were treated and evaluated their response to treatment.</description>
        <time_frame>2 years</time_frame>
        <population>Number of patients who achieved a clinical response</population>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab+DC/Myeloma Fusions/GM-CSF</title>
            <description>Nivolumab will be given every two weeks&#xD;
The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle&#xD;
Nivolumab: Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects your body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Nivolumab has been shown to react against cancer cells, including MM cells.&#xD;
DC/myeloma fusions/GM-CSF: The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing unique markers.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Achieve a Clinical Response (SD, PR, VGPR, CR)</title>
          <description>We looked at the two patients who were treated and evaluated their response to treatment.</description>
          <population>Number of patients who achieved a clinical response</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0</title>
        <description>We evaluated the number of patients who developed a related adverse event as assessed by the CTCAE version 4.0.</description>
        <time_frame>2 years</time_frame>
        <population>Patients who developed treatment-related adverse events</population>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab+DC/Myeloma Fusions/GM-CSF</title>
            <description>Nivolumab will be given every two weeks&#xD;
The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle&#xD;
Nivolumab: Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects your body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Nivolumab has been shown to react against cancer cells, including MM cells.&#xD;
DC/myeloma fusions/GM-CSF: The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing unique markers.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0</title>
          <description>We evaluated the number of patients who developed a related adverse event as assessed by the CTCAE version 4.0.</description>
          <population>Patients who developed treatment-related adverse events</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Who Are Alive Without Progression at 2 Years</title>
        <description>We calculated the number of patients who were alive without progression at 2 years</description>
        <time_frame>2 years</time_frame>
        <population>The number of patients who were alive without progression at 2 years</population>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab+DC/Myeloma Fusions/GM-CSF</title>
            <description>Nivolumab will be given every two weeks&#xD;
The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle&#xD;
Nivolumab: Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects your body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Nivolumab has been shown to react against cancer cells, including MM cells.&#xD;
DC/myeloma fusions/GM-CSF: The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing unique markers.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Are Alive Without Progression at 2 Years</title>
          <description>We calculated the number of patients who were alive without progression at 2 years</description>
          <population>The number of patients who were alive without progression at 2 years</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from the first dose of treatment through 30 days after the last dose of treatment up to 6 months. All-Cause Mortality monitored/assessed up to 2 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Nivolumab+DC/Myeloma Fusions/GM-CSF</title>
          <description>Nivolumab will be given every two weeks&#xD;
The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle&#xD;
Nivolumab: Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects your body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Nivolumab has been shown to react against cancer cells, including MM cells.&#xD;
DC/myeloma fusions/GM-CSF: The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing unique markers.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash, maculopapular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="2" subjects_at_risk="2"/>
              </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="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection Site Reaction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alkaline Phosphatase Increase</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>GGT increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle Weakness (lower limb)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pain, hip</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </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>
    <limitations_and_caveats>Due to withdrawal of funding, this study was halted prematurely. Only two participants were treated and we were unable to analyze the data in any meaningful way due to the small sample size.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Emma Logan, Director of Research Nursing</name_or_title>
      <organization>Beth Israel Deaconess Medical Center</organization>
      <phone>6176675984</phone>
      <email>eklogan@bidmc.harvard.edu</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/NCT03782064
org study id: 18-280
nct id: NCT03782064
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research study is studying a cancer vaccine called Dendritic Cell/MM Fusion vaccine
      (DC/MM vaccine) in combination with nivolumab, as a possible treatment for multiple myeloma
      (MM).

      The drugs involved in this study are:

        -  Dendritic Cell/MM Fusion vaccine (DC/MM vaccine)

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

      The FDA (the U.S. Food and Drug Administration) has not approved the DC/MM vaccine as a
      treatment for any disease.

      The FDA has not approved nivolumab for multiple myeloma. A similar immunotherapy drug used in
      combination with IMiDs (drugs that regulate or modify the immune system) was associated with
      higher risk of death in another research trial in patients with multiple myeloma; however,
      nivolumab has been approved for use in several other types of cancers.

      The FDA has not approved the combination of nivolumab with the DC/MM vaccine as a treatment
      for any disease.

      In this research study, the investigators wish to determine whether nivolumab administered in
      combination with the DC/MM vaccine will help promote an immune response against multiple
      myeloma cells.

      An immune response is any reaction by the immune system. It helps the body distinguish itself
      from substances foreign to it, such as infections and dangerous substances. Cancer cells have
      unique markers that distinguish them from normal cells, which can potentially serve as
      targets for the immune system.

      The DC/MM vaccine is an investigational agent that tries to help the immune system recognize
      and fight against cancer cells, utilizing those unique markers. Unlike a standard vaccine
      that is used to prevent infections, cancer vaccines are being studied to see if they can
      fight cancers that are already in the body. Laboratory studies suggest that when dendritic
      cells (a type of immune cell that helps to tell your immune system what is good and what is
      bad) and tumor cells are brought together, the dendritic cells can stimulate immune responses
      against the tumor.

      Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a
      type of protein that protects the body against foreign invaders, called antigens, by grabbing
      hold of antigens to stop them from invading your system. Monoclonal indicated that this
      antibody was made in a lab. Nivolumab has been shown to react against cancer cells, including
      MM cells. The investigators hope that the addition of nivolumab with the DC/MM vaccine will
      help the body fight MM
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients Who Develop Immunologic Response to Nivolumab and the DC/MM Fusion Vaccine
time frame: 2 years
description: We planned to evaluate the immunologic response to treatment in blood and bone marrow. Two patients were treated on protocol and both came off due to disease progression early in the course of therapy (one patient during cycle 1 and one patient during cycle 3.) As such, there is insufficient data to perform what had been planned in correlative science studies so no samples were analyzed. This study has been stopped and no further patients are being enrolled and no further samples are being collected. No data has been obtained for any immune analysis; therefore no immune or clinical data will be reported on this trial.
measure: Number of Patients Who Achieve a Clinical Response (SD, PR, VGPR, CR)
time frame: 2 years
description: We looked at the two patients who were treated and evaluated their response to treatment.
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
time frame: 2 years
description: We evaluated the number of patients who developed a related adverse event as assessed by the CTCAE version 4.0.
measure: Number of Patients Who Are Alive Without Progression at 2 Years
time frame: 2 years
description: We calculated the number of patients who were alive without progression at 2 years
arm group label: Nivolumab+DC/myeloma fusions/GM-CSF
arm group type: Experimental
description: Nivolumab will be given every two weeks
The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects your body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Nivolumab has been shown to react against cancer cells, including MM cells.
arm group label: Nivolumab+DC/myeloma fusions/GM-CSF
intervention type: Biological
intervention name: DC/myeloma fusions/GM-CSF
description: The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing unique markers.
arm group label: Nivolumab+DC/myeloma fusions/GM-CSF
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jacalyn Rosenblatt, MD
role: Principal Investigator
affiliation: Beth Israel Deaconess Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Beth Israel Deaconess Medical Center
investigator full name: Jacalyn Rosenblatt
investigator title: Principal Investigator
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Nivolumab
sharing ipd: Yes
ipd description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor-Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data can be shared no earlier than 1 year following the date of publication
ipd access criteria: Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to withdrawal of funding, this study was halted prematurely. Only two participants were treated and we were unable to analyze the data in any meaningful way due to the small sample size.
point of contact: 