<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/NCT02224599</url>
  </required_header>
  <id_info>
    <org_study_id>KIROVAX-003</org_study_id>
    <nct_id>NCT02224599</nct_id>
  </id_info>
  <brief_title>Cyclophosphamide, TAPA-Pulsed Dendritic Cell Therapy and Imiquimod in Progressive and/or Refractory Solid Malignancies</brief_title>
  <official_title>Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen-Pulsed Dendritic Cell Therapy and Imiquimod, in Patients With Progressive and/or Refractory Solid Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kiromic BioPharma Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kiromic BioPharma Inc.</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients diagnosed with progressive and/or refractory solid malignancies, who have failed&#xD;
      conventional therapy, and have no available, potentially curative therapeutic options, will&#xD;
      be candidates for this Phase I/II study. Following confirmation of disease progression and/or&#xD;
      refractoriness, eligible patients who agree to participate and sign an informed consent form&#xD;
      will have their tumor cells/tissues and/or blood analyzed for the expression of a specific&#xD;
      panel of Tumor Associated Peptide Antigens (TAPAs), including Sp17, ropporin, AKAP-4, PTTG1,&#xD;
      Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For patients whose tumors express one (1) or more of these TAPAs (Sp17, ropporin, AKAP-4,&#xD;
      PTTG1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1), whole blood will be obtained by&#xD;
      phlebotomy and/or leukapheresis performed for generation of autologous DCs. Patient's DCs&#xD;
      will be generated in Kiromic's Cell Processing GMP facility, according to established&#xD;
      Standard Operating Procedures, and activated by pulsing/loading them with the TAPA(s)&#xD;
      relevant for each particular patient. Patients will receive five (5) days of low-dose&#xD;
      cyclophosphamide 5 to 7 days prior to each vaccination with TAPA-pulsed DCs to decrease Treg&#xD;
      activity. Patients will also receive a single dose of topical Imiquimod cream after each&#xD;
      vaccination. TAPA-pulsed DCs will be administered at a fixed dose of up to 1 X 107 DCs. DC&#xD;
      vaccination schedule will be weekly via intradermal (ID) injections for a total of 3&#xD;
      vaccinations. Topical Imiquimod cream will also be administered once after the vaccination.&#xD;
      Patients will be followed on a weekly basis (or more frequently if required) to evaluate&#xD;
      treatment-related toxicity. Immune efficacy and anti-tumor responses will be evaluated per&#xD;
      protocol specifications. Continuation and stopping rules for the study will be defined based&#xD;
      on toxicity/tolerability (Phase I) and immune efficacy (Phase II).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor decision to terminate study due to poor accrual&#xD;
  </why_stopped>
  <start_date type="Actual">July 28, 2017</start_date>
  <completion_date type="Actual">August 30, 2018</completion_date>
  <primary_completion_date type="Actual">August 30, 2018</primary_completion_date>
  <phase>Phase 1/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>Adverse Events Due to Administration of TAPA-Pulse DC Vaccine</measure>
    <time_frame>Continuous for 45 days after the first dose.</time_frame>
    <description>Grade, causality, start/stop dates (duration), resolutions for adverse events will be monitored and recorded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immune Response</measure>
    <time_frame>Days -7, 22 and 45</time_frame>
    <description>The response of T-cells present in the peripheral blood mononuclear cells (PBMCs) population to the peptides used to pulse a patient's dendritic cell vaccine is evaluated by measuring the expression of Th1/CTL-type cytokines (IFN-γ and/or TNF-α and/or IL-17) by a standard ELI-Spot assay using 500,000 PBMCs per experimental replicate and a minimum of 3 experimental replicates for each stimulation. The results are expressed as the average number of spots obtained from the stimulation of 500,000 PBMCs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive DTH Skin Tests With Relevant TAPA</measure>
    <time_frame>Days -7, 22 and 45</time_frame>
    <description>DTH skin test will be performed on subject's forearm or within 5 cm from the site of prior DC vaccination, if possible</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Progressive Solid Malignancies</condition>
  <condition>Refractory Solid Malignancies</condition>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>CYP, TAPA-pulsed DC vaccine, Imiquimod</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TAPA-pulsed DC vaccine</intervention_name>
    <description>Subjects will given the vaccine which contains 1 x 10^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.</description>
    <arm_group_label>CYP, TAPA-pulsed DC vaccine, Imiquimod</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide Pill</intervention_name>
    <description>Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.</description>
    <arm_group_label>CYP, TAPA-pulsed DC vaccine, Imiquimod</arm_group_label>
    <other_name>Cytoxan®, Neosar®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Imiquimod Topical Cream</intervention_name>
    <description>Topical Imiquimod Cream will be applied after vaccination.</description>
    <arm_group_label>CYP, TAPA-pulsed DC vaccine, Imiquimod</arm_group_label>
    <other_name>Aldara Cream, Zyclara</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ability to provide informed consent.&#xD;
&#xD;
          2. Patients with histologically proven progressive and/or refractory SM, s/p conventional&#xD;
             salvage therapy, completed at least 3 weeks prior to study vaccination, will be&#xD;
             eligible for enrollment.&#xD;
&#xD;
          3. Expression of one (1) or more of the following TAPAs: Sp17, AKAP-4, Ropporin, PTTG-1,&#xD;
             Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1, by either RT-PCR and/or&#xD;
             immunocytochemistry, Western blotting or ELISA, in neoplastic cells and/or blood. For&#xD;
             HER-2/neu expression, positive FISH results are acceptable.&#xD;
&#xD;
          4. Presence of measurable or evaluable disease.&#xD;
&#xD;
          5. Patients must not have any active infectious process.&#xD;
&#xD;
          6. Patients must not have a history of HIV, or active Hepatitis A, B, and C.&#xD;
&#xD;
          7. Patients must not be receiving active immunosuppressive therapy.&#xD;
&#xD;
          8. Patients must have discontinued systemic cytotoxic or radiation therapy at least three&#xD;
             (3) weeks prior to vaccination and toxicities from previous therapies must be grade 1&#xD;
             or less. all other FDA approved forms of antineoplastic therapy are allowed such as&#xD;
             immunotherapy, targeted therapies, or hormonal therapies (67, 68)&#xD;
&#xD;
          9. Patients may not have any known allergy to CYP and/or Imiquimod.&#xD;
&#xD;
         10. Patients must be willing to provide at least 250 mL, and up to 500 mL, of whole blood&#xD;
             obtained by phlebotomy and/or consent to leukapheresis for DC generation.&#xD;
&#xD;
         11. Adequate renal and hepatic function (creatinine ≤ 2.0 mg/dl, bilirubin ≤ 2.0 mg/dl,&#xD;
             AST and ALT ≤ 4X upper limit of normal range).&#xD;
&#xD;
         12. Adequate hematologic function (Platelets ≥ 60,000/mm3, lymphocytes ≥ 1,000 mm3,&#xD;
             neutrophils ≥ 750/mm3, hemoglobin ≥ 9.0 g/dl).&#xD;
&#xD;
         13. Karnofsky performance status ≥ 70%.&#xD;
&#xD;
         14. Expected survival ≥ 6 months.&#xD;
&#xD;
         15. Either a female or male of reproductive capacity wishing to participate in this study&#xD;
             must be using, or agree to use, one or more types of birth control during the entire&#xD;
             study and for 3 months after completing the study. Birth control methods may include&#xD;
             condoms, diaphragms, birth control pills, spermicidal gels or foams, anti-gonadotropin&#xD;
             injections, intrauterine devices (IUD), surgical sterilization, or subcutaneous&#xD;
             implants. Another choice is for a subject's sexual partner to use one of these birth&#xD;
             control methods. Women of reproductive capacity will be required to undergo a urine&#xD;
             pregnancy test before completion of the post-screening informed consent process.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients without confirmed progressive and/or refractory SM using standard RECIST&#xD;
             criteria.&#xD;
&#xD;
          2. Patients without measurable or evaluable disease.&#xD;
&#xD;
          3. Patients receiving cytotoxic therapy or radiation therapy, within three (3) weeks of&#xD;
             vaccination.&#xD;
&#xD;
          4. Active immunosuppressive therapy, including non-physiologic systemic steroids&#xD;
             (excluding topical, intraocular, inhaled, and intranasal steroids) for any other&#xD;
             condition.&#xD;
&#xD;
          5. Persistent fever (&gt;24 hours) documented by repeated measurement or active,&#xD;
             uncontrolled infection within 4 weeks of enrollment.&#xD;
&#xD;
          6. Active ischemic heart disease or history of myocardial infarction within six months.&#xD;
&#xD;
          7. Active autoimmune disease, including, but not limited to, Systemic Lupus Erythematosus&#xD;
             (SLE), Multiple Sclerosis (MS), Ankylosing Spondylitis (AS), Inflammatory Bowel&#xD;
             Disease (IBD) and Rheumatoid Arthritis (RA).&#xD;
&#xD;
          8. Pregnancy or breast feeding.&#xD;
&#xD;
          9. Active second invasive malignancy, other than basal cell carcinoma of the skin.&#xD;
&#xD;
         10. Life expectancy of less than 6 months.&#xD;
&#xD;
         11. Patients with contraindications to CYP and/or Imiquimod.&#xD;
&#xD;
         12. Patients who have received organ transplants.&#xD;
&#xD;
         13. Patients with psychological or geographic conditions that prevent adequate follow- up&#xD;
             or compliance with the study protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anthony Tolcher, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NEXT Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <results_first_submitted>March 30, 2020</results_first_submitted>
  <results_first_submitted_qc>April 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 24, 2020</results_first_posted>
  <last_update_submitted>April 14, 2020</last_update_submitted>
  <last_update_submitted_qc>April 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Immunotherapy</keyword>
  <keyword>TAPA-Pulsed Dendritic Cell Therapy</keyword>
  <keyword>Dendritic Cell Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Imiquimod</mesh_term>
  </intervention_browse>
  <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>August 22, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT02224599/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 8, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT02224599/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>CYP, TAPA-pulsed DC Vaccine, Imiquimod</title>
          <description>TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream&#xD;
TAPA-pulsed DC vaccine: Subjects will given the vaccine which contains 1 x 10^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.&#xD;
Cyclophosphamide Pill: Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.&#xD;
Imiquimod Topical Cream: Topical Imiquimod Cream will be applied after vaccination.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progression of Disease</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>CYP, TAPA-pulsed DC Vaccine, Imiquimod</title>
          <description>TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream&#xD;
TAPA-pulsed DC vaccine: Subjects will given the vaccine which contains 1 x 10^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.&#xD;
Cyclophosphamide Pill: Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.&#xD;
Imiquimod Topical Cream: Topical Imiquimod Cream will be applied after vaccination.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50.33" spread="18.55"/>
                  </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="1"/>
                  </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="2"/>
                  </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>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Adverse Events Due to Administration of TAPA-Pulse DC Vaccine</title>
        <description>Grade, causality, start/stop dates (duration), resolutions for adverse events will be monitored and recorded.</description>
        <time_frame>Continuous for 45 days after the first dose.</time_frame>
        <population>Enrollment was terminated</population>
        <group_list>
          <group group_id="O1">
            <title>CYP, TAPA-pulsed DC Vaccine, Imiquimod</title>
            <description>TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream&#xD;
TAPA-pulsed DC vaccine: Subjects will given the vaccine which contains 1 x 10^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.&#xD;
Cyclophosphamide Pill: Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.&#xD;
Imiquimod Topical Cream: Topical Imiquimod Cream will be applied after vaccination.</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Events Due to Administration of TAPA-Pulse DC Vaccine</title>
          <description>Grade, causality, start/stop dates (duration), resolutions for adverse events will be monitored and recorded.</description>
          <population>Enrollment was terminated</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Immune Response</title>
        <description>The response of T-cells present in the peripheral blood mononuclear cells (PBMCs) population to the peptides used to pulse a patient's dendritic cell vaccine is evaluated by measuring the expression of Th1/CTL-type cytokines (IFN-γ and/or TNF-α and/or IL-17) by a standard ELI-Spot assay using 500,000 PBMCs per experimental replicate and a minimum of 3 experimental replicates for each stimulation. The results are expressed as the average number of spots obtained from the stimulation of 500,000 PBMCs</description>
        <time_frame>Days -7, 22 and 45</time_frame>
        <population>Enrollment was teriminated.</population>
        <group_list>
          <group group_id="O1">
            <title>CYP, TAPA-pulsed DC Vaccine, Imiquimod</title>
            <description>TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream&#xD;
TAPA-pulsed DC vaccine: Subjects will given the vaccine which contains 1 x 10^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.&#xD;
Cyclophosphamide Pill: Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.&#xD;
Imiquimod Topical Cream: Topical Imiquimod Cream will be applied after vaccination.</description>
          </group>
        </group_list>
        <measure>
          <title>Immune Response</title>
          <description>The response of T-cells present in the peripheral blood mononuclear cells (PBMCs) population to the peptides used to pulse a patient's dendritic cell vaccine is evaluated by measuring the expression of Th1/CTL-type cytokines (IFN-γ and/or TNF-α and/or IL-17) by a standard ELI-Spot assay using 500,000 PBMCs per experimental replicate and a minimum of 3 experimental replicates for each stimulation. The results are expressed as the average number of spots obtained from the stimulation of 500,000 PBMCs</description>
          <population>Enrollment was teriminated.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Positive DTH Skin Tests With Relevant TAPA</title>
        <description>DTH skin test will be performed on subject's forearm or within 5 cm from the site of prior DC vaccination, if possible</description>
        <time_frame>Days -7, 22 and 45</time_frame>
        <population>Enrollment was terminated</population>
        <group_list>
          <group group_id="O1">
            <title>CYP, TAPA-pulsed DC Vaccine, Imiquimod</title>
            <description>TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream&#xD;
TAPA-pulsed DC vaccine: Subjects will given the vaccine which contains 1 x 10^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.&#xD;
Cyclophosphamide Pill: Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.&#xD;
Imiquimod Topical Cream: Topical Imiquimod Cream will be applied after vaccination.</description>
          </group>
        </group_list>
        <measure>
          <title>Positive DTH Skin Tests With Relevant TAPA</title>
          <description>DTH skin test will be performed on subject's forearm or within 5 cm from the site of prior DC vaccination, if possible</description>
          <population>Enrollment was terminated</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 months</time_frame>
      <desc>Enrollment was terminated</desc>
      <group_list>
        <group group_id="E1">
          <title>CYP, TAPA-pulsed DC Vaccine, Imiquimod</title>
          <description>TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream&#xD;
TAPA-pulsed DC vaccine: Subjects will given the vaccine which contains 1 x 10^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.&#xD;
Cyclophosphamide Pill: Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.&#xD;
Imiquimod Topical Cream: Topical Imiquimod Cream will be applied after vaccination.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>CMO and Head of Clinical Operations</name_or_title>
      <organization>Kiromic</organization>
      <phone>(832) 968-4888</phone>
      <email>sdahlbeck@kiromic.com</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/NCT02224599
org study id: KIROVAX-003
nct id: NCT02224599
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Patients diagnosed with progressive and/or refractory solid malignancies, who have failed
      conventional therapy, and have no available, potentially curative therapeutic options, will
      be candidates for this Phase I/II study. Following confirmation of disease progression and/or
      refractoriness, eligible patients who agree to participate and sign an informed consent form
      will have their tumor cells/tissues and/or blood analyzed for the expression of a specific
      panel of Tumor Associated Peptide Antigens (TAPAs), including Sp17, ropporin, AKAP-4, PTTG1,
      Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1.
For patients whose tumors express one (1) or more of these TAPAs (Sp17, ropporin, AKAP-4,
      PTTG1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1), whole blood will be obtained by
      phlebotomy and/or leukapheresis performed for generation of autologous DCs. Patient's DCs
      will be generated in Kiromic's Cell Processing GMP facility, according to established
      Standard Operating Procedures, and activated by pulsing/loading them with the TAPA(s)
      relevant for each particular patient. Patients will receive five (5) days of low-dose
      cyclophosphamide 5 to 7 days prior to each vaccination with TAPA-pulsed DCs to decrease Treg
      activity. Patients will also receive a single dose of topical Imiquimod cream after each
      vaccination. TAPA-pulsed DCs will be administered at a fixed dose of up to 1 X 107 DCs. DC
      vaccination schedule will be weekly via intradermal (ID) injections for a total of 3
      vaccinations. Topical Imiquimod cream will also be administered once after the vaccination.
      Patients will be followed on a weekly basis (or more frequently if required) to evaluate
      treatment-related toxicity. Immune efficacy and anti-tumor responses will be evaluated per
      protocol specifications. Continuation and stopping rules for the study will be defined based
      on toxicity/tolerability (Phase I) and immune efficacy (Phase II).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events Due to Administration of TAPA-Pulse DC Vaccine
time frame: Continuous for 45 days after the first dose.
description: Grade, causality, start/stop dates (duration), resolutions for adverse events will be monitored and recorded.
measure: Immune Response
time frame: Days -7, 22 and 45
description: The response of T-cells present in the peripheral blood mononuclear cells (PBMCs) population to the peptides used to pulse a patient's dendritic cell vaccine is evaluated by measuring the expression of Th1/CTL-type cytokines (IFN-γ and/or TNF-α and/or IL-17) by a standard ELI-Spot assay using 500,000 PBMCs per experimental replicate and a minimum of 3 experimental replicates for each stimulation. The results are expressed as the average number of spots obtained from the stimulation of 500,000 PBMCs
measure: Positive DTH Skin Tests With Relevant TAPA
time frame: Days -7, 22 and 45
description: DTH skin test will be performed on subject's forearm or within 5 cm from the site of prior DC vaccination, if possible
arm group label: CYP, TAPA-pulsed DC vaccine, Imiquimod
arm group type: Experimental
description: TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream
intervention type: Biological
intervention name: TAPA-pulsed DC vaccine
description: Subjects will given the vaccine which contains 1 x 10^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.
arm group label: CYP, TAPA-pulsed DC vaccine, Imiquimod
intervention type: Drug
intervention name: Cyclophosphamide Pill
description: Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.
arm group label: CYP, TAPA-pulsed DC vaccine, Imiquimod
other name: Cytoxan®, Neosar®
intervention type: Drug
intervention name: Imiquimod Topical Cream
description: Topical Imiquimod Cream will be applied after vaccination.
arm group label: CYP, TAPA-pulsed DC vaccine, Imiquimod
other name: Aldara Cream, Zyclara
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Anthony Tolcher, MD
role: Principal Investigator
affiliation: NEXT Oncology
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Cyclophosphamide
mesh term: Imiquimod
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 