<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/NCT03042793</url>
  </required_header>
  <id_info>
    <org_study_id>MY0001</org_study_id>
    <secondary_id>2016-000990-19</secondary_id>
    <nct_id>NCT03042793</nct_id>
  </id_info>
  <brief_title>Vaccination With PD-L1 Peptide Against Multiple Myeloma</brief_title>
  <official_title>Vaccination With PD-L1 Peptide With Montanide Against Multiple Myeloma After High Dose Chemotherapy With Stem Cell Support. A Phase I First-in-human Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lene Meldgaard Knudsen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Herlev Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Title: Vaccination with PD-L1 peptide with Montanide against multiple myeloma after high dose&#xD;
      chemotherapy with stem cell support. A phase I first-in-human study.&#xD;
&#xD;
      Hypothesis: In this trial the investigators assess a new immunotherapeutic strategy targeting&#xD;
      the immune checkpoint molecule PD-L1 to investigate the potential of vaccination against&#xD;
      PD-L1 as a possible anticancer target.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Multiple myeloma is the second most common hematologic cancer which is despite&#xD;
      advances in treatment is still incurable for most patients.&#xD;
&#xD;
      In this trial the investigators assess a new immunotherapeutic strategy targeting the immune&#xD;
      checkpoint molecule PD-L1 to investigate the potential of vaccination against PD-L1 as a&#xD;
      possible anticancer target.&#xD;
&#xD;
      PD-L1 has been recognized as an important factor in immune regulation and development of&#xD;
      immune tolerance in the microenvironment of cancer cells. Cells that express PD-L1 on their&#xD;
      surface are known to inhibit the immune system. As seen with the recent advances in&#xD;
      immunotherapy against cancer with antibodies against PD-L1, the the immunosuppressive role of&#xD;
      the molecule PD-L1 can be antagonized to the benefit of patients with cancer. PD-L1 is&#xD;
      expressed on both cancer cells, antigen presenting cells and immunosuppressive cells in the&#xD;
      tumor micro-environment. Vaccination against PD-L1 is therefore two sided. The investigators&#xD;
      aim to stimulate PD-L1 specific T-cells, hence eliminating both PD-L1 positive tumor cells as&#xD;
      well as PD-L1 positive immunosuppressive and antigen presenting cells in the tumor&#xD;
      microenvironment. The primary endpoints are safety and toxicity evaluation. Secondary&#xD;
      endpoint is immunological response. Clinical response will be described.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2017</start_date>
  <completion_date type="Actual">May 14, 2020</completion_date>
  <primary_completion_date type="Actual">May 14, 2020</primary_completion_date>
  <phase>Phase 1</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>Incidence of toxicity</measure>
    <time_frame>12 months</time_frame>
    <description>CTCAE = Common Terminology Criteria for Adverse Events v. 4.0 will be used for registration of toxicity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of immunological responses</measure>
    <time_frame>12 months</time_frame>
    <description>Immunological assays will be used to identify immunological responses.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Clinical response</measure>
    <time_frame>12 months</time_frame>
    <description>Will be described according to standard IMWG-criteria for multiple myeloma.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Vaccination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccine: PD-L1 peptide.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PD-L1 peptide vaccine</intervention_name>
    <description>PD-L1 peptide given subcutaneously with Montanide ISA-51</description>
    <arm_group_label>Vaccination</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically verified multiple myeloma&#xD;
&#xD;
          2. Newly treated with HDT and no signs of relapse&#xD;
&#xD;
          3. Age ≥18 years&#xD;
&#xD;
          4. Performance status ≤ 2 (ECOG-scale)&#xD;
&#xD;
          5. Expected survival &gt; 3 months&#xD;
&#xD;
          6. Sufficiently regenerated bone marrow function, i.e.&#xD;
&#xD;
               1. Leucocytes ≥ 1,5 x 109&#xD;
&#xD;
               2. Granulocytes ≥ 1,0 x 109&#xD;
&#xD;
               3. Thrombocytes ≥ 20 x 109&#xD;
&#xD;
          7. Creatinine &lt; 2.5 upper normal limit, i.e. &lt; 300 μmol/l&#xD;
&#xD;
          8. Sufficient liver function, i.e.&#xD;
&#xD;
               1. ALAT &lt; 2.5 upper normal limit, i.e. ALAT &lt;112 U/l&#xD;
&#xD;
               2. Bilirubin &lt; 30 U/l&#xD;
&#xD;
          9. Women agreement to use contraceptive methods with a failure rate of &lt; 1% per year&#xD;
             during the treatment period and for at least 120 days after the last treatment.&#xD;
&#xD;
         10. For men: agreement to use contraceptive measures and agreement to refrain from&#xD;
             donating sperm.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Non-secretory myeloma&#xD;
&#xD;
          2. Other malignancies in the medical history excluding squamous cell carcinoma of the&#xD;
             skin and patients cured for another malignant disease with no sign of relapse three&#xD;
             years after ended treatment.&#xD;
&#xD;
          3. Significant medical condition per investigators judgement e.g. severe Asthma/COPD,&#xD;
             poorly regulated heart condition, insulin dependent diabetes mellitus.&#xD;
&#xD;
          4. Acute or chronic viral infection e.g. HIV, hepatitis or tuberculosis&#xD;
&#xD;
          5. Serious known allergies or earlier anaphylactic reactions.&#xD;
&#xD;
          6. Known sensibility towards Montanide ISA-51&#xD;
&#xD;
          7. Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or&#xD;
             hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis,&#xD;
             autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis&#xD;
             etc.&#xD;
&#xD;
          8. Pregnant and breastfeeding women.&#xD;
&#xD;
          9. Fertile women not using secure contraception with a failure rate less than &lt; 1%&#xD;
&#xD;
         10. Patients taking immune suppressive medications incl. corticosteroids and methotrexate&#xD;
             at the time of enrollment&#xD;
&#xD;
         11. Psychiatric disorders that per investigator judgment could influence compliance.&#xD;
&#xD;
         12. Treatment with other experimental drugs&#xD;
&#xD;
         13. Treatment with other anti-cancer drugs - except bisphosphonates and denosumab&#xD;
&#xD;
         14. Patients with active uncontrolled hypercalcemia&#xD;
&#xD;
         15. Patients who have received chemotherapy, immune therapy, radiation therapy within the&#xD;
             last 28 days.&#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>Nicolai Jørgensen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Center for Cancer Immune Therapy, Universityhospital Herlev and Gentofte</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Hematology, Universityhospital Herlev and Gentofte</name>
      <address>
        <city>Herlev</city>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>February 2, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>July 2, 2020</last_update_submitted>
  <last_update_submitted_qc>July 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Herlev Hospital</investigator_affiliation>
    <investigator_full_name>Lene Meldgaard Knudsen</investigator_full_name>
    <investigator_title>MD, DMSc, Head of Department, Department of Haematology, Universityhospital Herlev and Gentofte</investigator_title>
  </responsible_party>
  <keyword>myeloma</keyword>
  <keyword>vaccination</keyword>
  <keyword>PD-L1</keyword>
  <keyword>peptide vaccine</keyword>
  <keyword>cancer vaccine</keyword>
  <keyword>immunotherapy</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>
  <!-- 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/NCT03042793
org study id: MY0001
secondary id: 2016-000990-19
nct id: NCT03042793
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Title: Vaccination with PD-L1 peptide with Montanide against multiple myeloma after high dose
      chemotherapy with stem cell support. A phase I first-in-human study.

      Hypothesis: In this trial the investigators assess a new immunotherapeutic strategy targeting
      the immune checkpoint molecule PD-L1 to investigate the potential of vaccination against
      PD-L1 as a possible anticancer target.
Background: Multiple myeloma is the second most common hematologic cancer which is despite
      advances in treatment is still incurable for most patients.

      In this trial the investigators assess a new immunotherapeutic strategy targeting the immune
      checkpoint molecule PD-L1 to investigate the potential of vaccination against PD-L1 as a
      possible anticancer target.

      PD-L1 has been recognized as an important factor in immune regulation and development of
      immune tolerance in the microenvironment of cancer cells. Cells that express PD-L1 on their
      surface are known to inhibit the immune system. As seen with the recent advances in
      immunotherapy against cancer with antibodies against PD-L1, the the immunosuppressive role of
      the molecule PD-L1 can be antagonized to the benefit of patients with cancer. PD-L1 is
      expressed on both cancer cells, antigen presenting cells and immunosuppressive cells in the
      tumor micro-environment. Vaccination against PD-L1 is therefore two sided. The investigators
      aim to stimulate PD-L1 specific T-cells, hence eliminating both PD-L1 positive tumor cells as
      well as PD-L1 positive immunosuppressive and antigen presenting cells in the tumor
      microenvironment. The primary endpoints are safety and toxicity evaluation. Secondary
      endpoint is immunological response. Clinical response will be described.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of toxicity
time frame: 12 months
description: CTCAE = Common Terminology Criteria for Adverse Events v. 4.0 will be used for registration of toxicity
measure: Evaluation of immunological responses
time frame: 12 months
description: Immunological assays will be used to identify immunological responses.
measure: Clinical response
time frame: 12 months
description: Will be described according to standard IMWG-criteria for multiple myeloma.
arm group label: Vaccination
arm group type: Experimental
description: Vaccine: PD-L1 peptide.
intervention type: Biological
intervention name: PD-L1 peptide vaccine
description: PD-L1 peptide given subcutaneously with Montanide ISA-51
arm group label: Vaccination
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nicolai Jørgensen, MD
role: Principal Investigator
affiliation: Center for Cancer Immune Therapy, Universityhospital Herlev and Gentofte
facility: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Herlev Hospital
investigator full name: Lene Meldgaard Knudsen
investigator title: MD, DMSc, Head of Department, Department of Haematology, Universityhospital Herlev and Gentofte
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell