<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/NCT02193347</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00054746</org_study_id>
    <nct_id>NCT02193347</nct_id>
  </id_info>
  <brief_title>IDH1 Peptide Vaccine for Recurrent Grade II Glioma</brief_title>
  <acronym>RESIST</acronym>
  <official_title>Patients With IDH1 Positive Recurrent Grade II Glioma Enrolled in a Safety and Immunogenicity Study of Tumor-Specific Peptide Vaccine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gary Archer Ph.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Potential subjects with progressive Grade II primary brain tumor that have IDH1 positive&#xD;
      testing from the primary tumor (initial diagnosis) will be offered this treatment study in&#xD;
      order to test the safety of the PEPIDH1M vaccine in combination with standard chemotherapy&#xD;
      (temozolomide).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After informed consent has been signed, subjects will undergo standard of care vaccination&#xD;
      with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid&#xD;
      muscle to ensure adequate immunity to the tetanus antigen.&#xD;
&#xD;
      Eligible subjects will undergo a 1-2 hour leukapheresis (to pull off white blood cells) for&#xD;
      immune monitoring. Within 48 hours of leukapheresis, subjects will receive vaccine site&#xD;
      pre-conditioning as a single dose of Td toxoid (in a total volume of 0.4 mLs salt&#xD;
      water/saline) given in the intradermal space (just under the surface of the skin) to the&#xD;
      right groin area. The pre-conditioning will be administered one day prior to receiving&#xD;
      PEPIDH1M vaccine. The peptide vaccine is administered in the upper thigh area approximately 4&#xD;
      inches below the groin in the intradermal space as vaccine # 1. Subsequent vaccines will be&#xD;
      given on day 15 ±3 days (vaccine #2) and day 29 ±3 days (vaccine #3). Each injection of the&#xD;
      peptide vaccine will be given half on the right groin and half on the left groin. The first 3&#xD;
      peptide vaccine injections will occur without temozolomide (standard of care chemotherapy).&#xD;
&#xD;
      Seven to twelve days after the 3rd vaccine, subjects will have standard of care surgery to&#xD;
      remove the tumor. Tumor samples will be evaluated for the IDH1 markers and analyzed for other&#xD;
      cells that may have entered the tumor.&#xD;
&#xD;
      Based on the the tissue obtained at surgery, subjects with stable histologic grade at&#xD;
      recurrence will then be treated with vaccine and temozolomide. During monthly cycles of&#xD;
      temozolomide, subjects will receive the vaccine on day 22 (+ 2 days) for a maximum of 15&#xD;
      total vaccines (which includes the first 3 bi-weekly vaccines). Patients that have&#xD;
      transitioned to a higher grade brain tumor at the time of surgery will receive temozolomide&#xD;
      and radiation therapy per standard of care and monthly vaccines (vaccines #4-6). After&#xD;
      completion of radiation therapy, subjects in this treatment group will receive vaccines&#xD;
      monthly on day 22 (+2 days) with post-RT cycles of TMZ to a maximum of 15 vaccines.&#xD;
&#xD;
      All Adverse Events will be collected from time of consent until off study. The treatment&#xD;
      phase of the study will end 1 month after the last vaccine. Patients will be followed only&#xD;
      for overall survival, progression-free survival, and subsequent therapies thereafter.&#xD;
&#xD;
      Subjects will have blood collected for immune monitoring and biomarker testing during the&#xD;
      following times: prior to initiating vaccine therapy (at the leukapheresis visit), prior to&#xD;
      surgery to remove the tumor, at the clinic visit prior to starting first cycle of&#xD;
      temozolomide after surgery (or radiation therapy and temozolomide for those who transition to&#xD;
      higher grade), at vaccine #6, and at end of vaccine treatment (1 month after vaccine #15 or&#xD;
      time the subject comes off study, whichever comes first).&#xD;
&#xD;
      Subjects will be imaged with contrast-enhanced magnetic resonance imaging (MRI) according to&#xD;
      standard of care every 10 weeks (+/- 4 weeks) while on temozolomide and afterward, per the&#xD;
      treating neuro-oncologist's recommendation. Revised Assessment in Neuro-Oncology (RANO)&#xD;
      criteria will be used for assessment of pseudoprogression and tumor progression. Subjects&#xD;
      demonstrating definitive progression will be removed from study.&#xD;
&#xD;
      As part of standard care for these subjects, upon tumor progression, participants may undergo&#xD;
      biopsy or resection. As this is not a research procedure, consent will be obtained&#xD;
      separately. Subjects that have this procedure done within the Duke University Health System&#xD;
      will be asked to have a portion of the tumor sample, if possible, to assess immunologic cell&#xD;
      infiltration, antigen expression, and biomarkers for immunologic response.&#xD;
&#xD;
      Please note, data collection will continue to occur outside of the defined primary and&#xD;
      secondary outcomes for exploratory objectives.&#xD;
&#xD;
      The specific exploratory objective involves describing the progression free survival (PFS)&#xD;
      and overall survival (OS). The endpoint is the proportion of patients alive without disease&#xD;
      progression 6 months after initial vaccine treatment, and both the median PFS, and the median&#xD;
      OS.&#xD;
&#xD;
      The objective will be reviewed at 3 years after the last subject came off study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 28, 2016</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Actual">February 3, 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>Percentage of Participants With an Unacceptable Toxicity</measure>
    <time_frame>Date of consent through 2 months after the last vaccination</time_frame>
    <description>The percentage of patients who experience an unacceptable toxicity defined as any Grade 3 toxicity at least possibly attributed to the vaccine (or vaccine + TMZ and/or RT) that does not resolve to baseline within 3 weeks, any Grade 3 hypersensitivity reactions requiring steroids, any Grade 4 toxicity, including neurologic events not due to progressive disease, or any life threatening-event not attributable to concomitant medication, co-morbid event, or disease progression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Evaluable Subjects Who Had a Response Greater Than 20 Spot-forming Cells (SFC) Per 10^6 Lymphocytes</measure>
    <time_frame>From time of pheresis #1, one day prior to first pre-surgery vaccine dose, until the time of the third post-surgery vaccination, an expected average of 24 weeks after study initiation</time_frame>
    <description>The number of spot-forming cells (SFC) per 10^6 lymphocytes measured by ELISpot. A blue-black colored precipitate forms and appears as spots at the sites of cytokine localization, with each individual spot representing an individual analyte-secreting cell.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Brain Cancer</condition>
  <condition>Brain Neoplasm, Primary</condition>
  <condition>Brain Neoplasms, Recurrent</condition>
  <condition>Brain Tumor</condition>
  <condition>Cancer of the Brain</condition>
  <arm_group>
    <arm_group_label>PEPIDH1M vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PEPIDH1M vaccine</intervention_name>
    <description>PEPIDH1M vaccine is made up of 500 µg of 25 amino acid peptide administered with 150 µg of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally. The peptide vaccine is administered in the groin area approximately 10 cm below the inguinal ligament.</description>
    <arm_group_label>PEPIDH1M vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Tetanus-Diphtheria Toxoid (Td)</intervention_name>
    <description>After consent has been signed, all subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Within 48 hours of leukapheresis, subjects will receive a vaccine site pre-conditioning as a single dose of Td toxoid (1 flocculation unit, Lf, in a total volume of 0.4 mLs saline) administered intradermally to the right side of the groin one day prior to receiving the first PEPIDH1M vaccine.</description>
    <arm_group_label>PEPIDH1M vaccine</arm_group_label>
    <other_name>Tenivac</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>Subjects are treated with temozolomide (TMZ) at a targeted dose of 50-100mg/m2/d for 21 days every 28 days for up to 12 cycles. Subjects that have transitioned to a higher grade brain tumor at time of surgery will receive TMZ and radiation therapy per standard of care before starting TMZ cycles.</description>
    <arm_group_label>PEPIDH1M vaccine</arm_group_label>
    <other_name>Temodar</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years.&#xD;
&#xD;
          2. IDH1R132H expression in primary tumor&#xD;
&#xD;
          3. Radiographic and/or clinical progressive and resectable Grade II glioma.&#xD;
&#xD;
          4. Signed informed consent.&#xD;
&#xD;
          5. For females of child-bearing potential, negative serum pregnancy test at screening&#xD;
             (within 48 hours prior to leukapheresis)&#xD;
&#xD;
          6. Women of childbearing potential and male participants must agree to practice adequate&#xD;
             contraception.&#xD;
&#xD;
          7. Karnofsky Performance Status (KPS) of ≥ 70.&#xD;
&#xD;
          8. Complete Blood Count (CBC)/differential with adequate bone marrow function as defined&#xD;
             below within 2 weeks of enrollment:&#xD;
&#xD;
               -  Absolute neutrophil count, ≥ 1500 cells/mm3.&#xD;
&#xD;
               -  Platelet count, ≥ 100,000 cells/mm3.&#xD;
&#xD;
               -  Hemoglobin ≥ 10 g/dl. (Note: the use of transfusion or other intervention to&#xD;
                  achieve Hgb ≥ 10 g/dl is acceptable.)&#xD;
&#xD;
          9. Adequate renal function as defined below within 2 weeks of enrollment:&#xD;
&#xD;
               -  Blood Urea Nitrogen (BUN) ≤ 25 mg/dl.&#xD;
&#xD;
               -  Creatinine ≤ 1.7 mg/dl.&#xD;
&#xD;
         10. Adequate hepatic function as defined below within 2 weeks of enrollment:&#xD;
&#xD;
               -  Bilirubin ≤ 2.0 mg/dl.&#xD;
&#xD;
               -  Alanine Aminotransferase (ALT) ≤ 3 x normal range.&#xD;
&#xD;
               -  Aspartate Aminotransferase (AST) ≤ 3 x normal range&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease&#xD;
             free for ≥ 3 years. (For example, carcinoma in situ of the breast, oral cavity, and&#xD;
             cervix are all permissible.)&#xD;
&#xD;
          2. Metastases detected below the tentorium or beyond the cranial vault.&#xD;
&#xD;
          3. Severe, active co-morbidity, defined as follows:&#xD;
&#xD;
               -  Unstable angina and/or congestive heart failure requiring hospitalization.&#xD;
&#xD;
               -  Myocardial infarction within the last 6 months.&#xD;
&#xD;
               -  Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition;&#xD;
                  note, however, that HIV testing is not required for entry into this protocol. The&#xD;
                  need to exclude patients with AIDS from this protocol is necessary because&#xD;
                  treatments involved in this protocol may be significantly immunosuppressive.&#xD;
&#xD;
               -  Major medical illnesses or psychiatric impairments that in the investigator's&#xD;
                  opinion will prevent administration or completion of protocol therapy.&#xD;
&#xD;
          4. Pregnant or lactating women, due to possible adverse effects on the developing fetus&#xD;
             or infant due to study drug.&#xD;
&#xD;
          5. Prior allergic reaction to temozolomide.&#xD;
&#xD;
          6. Patients treated on any other therapeutic clinical protocols within 30 days prior to&#xD;
             study entry or during participation in the study.&#xD;
&#xD;
          7. Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any&#xD;
             component of Leukine®.&#xD;
&#xD;
          8. Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus&#xD;
             vaccine.&#xD;
&#xD;
          9. Unable to undergo MRI imaging.&#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>Katherine Peters, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 2, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <results_first_submitted>February 19, 2021</results_first_submitted>
  <results_first_submitted_qc>February 19, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 15, 2021</results_first_posted>
  <last_update_submitted>February 19, 2021</last_update_submitted>
  <last_update_submitted_qc>February 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Gary Archer Ph.D.</investigator_full_name>
    <investigator_title>Assistant Professor Neurosurgery</investigator_title>
  </responsible_party>
  <keyword>Immunotherapy</keyword>
  <keyword>Adult</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</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>October 11, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT02193347/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>PEPIDH1M Vaccine</title>
          <description>PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.&#xD;
PEPIDH1M vaccine: PEPIDH1M vaccine is made up of 500 µg of 25 amino acid peptide administered with 150 µg of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally. The peptide vaccine is administered in the groin area approximately 10 cm below the inguinal ligament.&#xD;
Tetanus-Diphtheria Toxoid (Td): After consent has been signed, all subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Within 48 hours of leukapheresis, subjects will receive a vaccine site pre-conditioning as a single dose of Td toxoid (1 flocculation unit, Lf, in a total volume of 0.4 mLs saline) administered intradermally to the right side of the groin one day prior to receiving the first PEPIDH1M vaccine.&#xD;
Temozolomide: Subjects are treated with temozolomide (TMZ) at a targeted dose of 50-100mg/m2/d for 21 days every 28 days for up to 12 cycles. Subjects that have transitioned to a higher grade brain tumor at time of surgery will receive TMZ and radiation therapy per standard of care before starting TMZ cycles.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>PEPIDH1M Vaccine</title>
          <description>PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.&#xD;
PEPIDH1M vaccine: PEPIDH1M vaccine is made up of 500 µg of 25 amino acid peptide administered with 150 µg of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally. The peptide vaccine is administered in the groin area approximately 10 cm below the inguinal ligament.&#xD;
Tetanus-Diphtheria Toxoid (Td): After consent has been signed, all subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Within 48 hours of leukapheresis, subjects will receive a vaccine site pre-conditioning as a single dose of Td toxoid (1 flocculation unit, Lf, in a total volume of 0.4 mLs saline) administered intradermally to the right side of the groin one day prior to receiving the first PEPIDH1M vaccine.&#xD;
Temozolomide: Subjects are treated with temozolomide (TMZ) at a targeted dose of 50-100mg/m2/d for 21 days every 28 days for up to 12 cycles. Subjects that have transitioned to a higher grade brain tumor at time of surgery will receive TMZ and radiation therapy per standard of care before starting TMZ cycles.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="24"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="43.83" spread="11.25"/>
                  </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="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="24"/>
                  </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>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With an Unacceptable Toxicity</title>
        <description>The percentage of patients who experience an unacceptable toxicity defined as any Grade 3 toxicity at least possibly attributed to the vaccine (or vaccine + TMZ and/or RT) that does not resolve to baseline within 3 weeks, any Grade 3 hypersensitivity reactions requiring steroids, any Grade 4 toxicity, including neurologic events not due to progressive disease, or any life threatening-event not attributable to concomitant medication, co-morbid event, or disease progression.</description>
        <time_frame>Date of consent through 2 months after the last vaccination</time_frame>
        <group_list>
          <group group_id="O1">
            <title>PEPIDH1M Vaccine</title>
            <description>PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.&#xD;
PEPIDH1M vaccine: PEPIDH1M vaccine is made up of 500 µg of 25 amino acid peptide administered with 150 µg of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally. The peptide vaccine is administered in the groin area approximately 10 cm below the inguinal ligament.&#xD;
Tetanus-Diphtheria Toxoid (Td): After consent has been signed, all subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Within 48 hours of leukapheresis, subjects will receive a vaccine site pre-conditioning as a single dose of Td toxoid (1 flocculation unit, Lf, in a total volume of 0.4 mLs saline) administered intradermally to the right side of the groin one day prior to receiving the first PEPIDH1M vaccine.&#xD;
Temozolomide: Subjects are treated with temozolomide (TMZ) at a targeted dose of 50-100mg/m2/d for 21 days every 28 days for up to 12 cycles. Subjects that have transitioned to a higher grade brain tumor at time of surgery will receive TMZ and radiation therapy per standard of care before starting TMZ cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With an Unacceptable Toxicity</title>
          <description>The percentage of patients who experience an unacceptable toxicity defined as any Grade 3 toxicity at least possibly attributed to the vaccine (or vaccine + TMZ and/or RT) that does not resolve to baseline within 3 weeks, any Grade 3 hypersensitivity reactions requiring steroids, any Grade 4 toxicity, including neurologic events not due to progressive disease, or any life threatening-event not attributable to concomitant medication, co-morbid event, or disease progression.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </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>Percentage of Evaluable Subjects Who Had a Response Greater Than 20 Spot-forming Cells (SFC) Per 10^6 Lymphocytes</title>
        <description>The number of spot-forming cells (SFC) per 10^6 lymphocytes measured by ELISpot. A blue-black colored precipitate forms and appears as spots at the sites of cytokine localization, with each individual spot representing an individual analyte-secreting cell.</description>
        <time_frame>From time of pheresis #1, one day prior to first pre-surgery vaccine dose, until the time of the third post-surgery vaccination, an expected average of 24 weeks after study initiation</time_frame>
        <population>Data not collected on three participants.</population>
        <group_list>
          <group group_id="O1">
            <title>PEPIDH1M Vaccine</title>
            <description>PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.&#xD;
PEPIDH1M vaccine: PEPIDH1M vaccine is made up of 500 µg of 25 amino acid peptide administered with 150 µg of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally. The peptide vaccine is administered in the groin area approximately 10 cm below the inguinal ligament.&#xD;
Tetanus-Diphtheria Toxoid (Td): After consent has been signed, all subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Within 48 hours of leukapheresis, subjects will receive a vaccine site pre-conditioning as a single dose of Td toxoid (1 flocculation unit, Lf, in a total volume of 0.4 mLs saline) administered intradermally to the right side of the groin one day prior to receiving the first PEPIDH1M vaccine.&#xD;
Temozolomide: Subjects are treated with temozolomide (TMZ) at a targeted dose of 50-100mg/m2/d for 21 days every 28 days for up to 12 cycles. Subjects that have transitioned to a higher grade brain tumor at time of surgery will receive TMZ and radiation therapy per standard of care before starting TMZ cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Evaluable Subjects Who Had a Response Greater Than 20 Spot-forming Cells (SFC) Per 10^6 Lymphocytes</title>
          <description>The number of spot-forming cells (SFC) per 10^6 lymphocytes measured by ELISpot. A blue-black colored precipitate forms and appears as spots at the sites of cytokine localization, with each individual spot representing an individual analyte-secreting cell.</description>
          <population>Data not collected on three participants.</population>
          <units>percentage of evaluable subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>5 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>PEPIDH1M Vaccine</title>
          <description>PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.&#xD;
PEPIDH1M vaccine: PEPIDH1M vaccine is made up of 500 µg of 25 amino acid peptide administered with 150 µg of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally. The peptide vaccine is administered in the groin area approximately 10 cm below the inguinal ligament.&#xD;
Tetanus-Diphtheria Toxoid (Td): After consent has been signed, all subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Within 48 hours of leukapheresis, subjects will receive a vaccine site pre-conditioning as a single dose of Td toxoid (1 flocculation unit, Lf, in a total volume of 0.4 mLs saline) administered intradermally to the right side of the groin one day prior to receiving the first PEPIDH1M vaccine.&#xD;
Temozolomide: Subjects are treated with temozolomide (TMZ) at a targeted dose of 50-100mg/m2/d for 21 days every 28 days for up to 12 cycles. Subjects that have transitioned to a higher grade brain tumor at time of surgery will receive TMZ and radiation therapy per standard of care before starting TMZ cycles.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>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="24" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Ventricular arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Other, Specify: CELLULITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="24" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Other, Specify: &quot;INNER EAR PRESSURE&quot;</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: BLOOD TINGED DRAINAGE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: CLICKING SOUND IN LEFT EAR</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: HEARS CLINKING SOUND IN HEAD INTERMITTENTLY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: INTERMITTENT PAIN, TWITCHING, AND/OR NUMBNESS UNDER RIGHT EYE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: INTERMITTENT; OBJECTS APPEAR TO MOVE OR SHAKE WHEN HOLDING</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: L EYELID EDEMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: SEEING A &quot;BROWNISH TINTED VERTICAL STRIPE&quot; FROM RIGHT EYE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: TUNNEL VISION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Floaters</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: CELLULITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: COLD SORES</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: HEAD INCISION WITH DRAINAGE AND TENDERNESS; 2+ SERRATIA MARCESCENS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: INCISION, ABNORMAL TISSUE CULTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: SHINGLES</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: WOUND INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: LEFT WRIST WOUND</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: LOWER BACK INJURY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: MVA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Muscle weakness left-sided</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Muscle weakness right-sided</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Muscle weakness upper limb</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Other, Specify: BUMPS ON R FOREARM</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: L WRIST BUMP/NODULE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Concentration impairment</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dysphasia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Facial nerve disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Movements involuntary</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: AURA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: DECREASED CIRCULATION IN FEET; BILATERAL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: FOREHEAD NUMBNESS. POST INJECTION #1.</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: INTRACRANIAL ANEURYSM, NONRUPTURED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: L HEMIPARESIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: L SIDED NEGLECT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: NIGHTMARES</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: PSEUDOMENINGOCELE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pyramidal tract syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hallucinations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: &quot;PASSING AIR WHEN URINATING&quot;</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urinary urgency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Other, Specify: LUMP IN LEFT BREAST</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Testicular pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Scalp pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: FLUID FILLED POCKET ON R FOREHEAD FROM SURGERY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: FLUID POCKET</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: RASH</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: RIGHT LOWER EXTREMITY. SKIN DISCOLORATION.</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: SKIN BUMP</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Other, Specify: SKIN SLOUGHING</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Skin induration</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <point_of_contact>
      <name_or_title>Katy Peters, M.D., Ph.D.</name_or_title>
      <organization>Duke University</organization>
      <phone>919-684-6173</phone>
      <email>katherine.peters@duke.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/NCT02193347
org study id: Pro00054746
nct id: NCT02193347
lead sponsor: 
has dmc: Yes
Potential subjects with progressive Grade II primary brain tumor that have IDH1 positive
      testing from the primary tumor (initial diagnosis) will be offered this treatment study in
      order to test the safety of the PEPIDH1M vaccine in combination with standard chemotherapy
      (temozolomide).
After informed consent has been signed, subjects will undergo standard of care vaccination
      with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid
      muscle to ensure adequate immunity to the tetanus antigen.

      Eligible subjects will undergo a 1-2 hour leukapheresis (to pull off white blood cells) for
      immune monitoring. Within 48 hours of leukapheresis, subjects will receive vaccine site
      pre-conditioning as a single dose of Td toxoid (in a total volume of 0.4 mLs salt
      water/saline) given in the intradermal space (just under the surface of the skin) to the
      right groin area. The pre-conditioning will be administered one day prior to receiving
      PEPIDH1M vaccine. The peptide vaccine is administered in the upper thigh area approximately 4
      inches below the groin in the intradermal space as vaccine # 1. Subsequent vaccines will be
      given on day 15 ±3 days (vaccine #2) and day 29 ±3 days (vaccine #3). Each injection of the
      peptide vaccine will be given half on the right groin and half on the left groin. The first 3
      peptide vaccine injections will occur without temozolomide (standard of care chemotherapy).

      Seven to twelve days after the 3rd vaccine, subjects will have standard of care surgery to
      remove the tumor. Tumor samples will be evaluated for the IDH1 markers and analyzed for other
      cells that may have entered the tumor.

      Based on the the tissue obtained at surgery, subjects with stable histologic grade at
      recurrence will then be treated with vaccine and temozolomide. During monthly cycles of
      temozolomide, subjects will receive the vaccine on day 22 (+ 2 days) for a maximum of 15
      total vaccines (which includes the first 3 bi-weekly vaccines). Patients that have
      transitioned to a higher grade brain tumor at the time of surgery will receive temozolomide
      and radiation therapy per standard of care and monthly vaccines (vaccines #4-6). After
      completion of radiation therapy, subjects in this treatment group will receive vaccines
      monthly on day 22 (+2 days) with post-RT cycles of TMZ to a maximum of 15 vaccines.

      All Adverse Events will be collected from time of consent until off study. The treatment
      phase of the study will end 1 month after the last vaccine. Patients will be followed only
      for overall survival, progression-free survival, and subsequent therapies thereafter.

      Subjects will have blood collected for immune monitoring and biomarker testing during the
      following times: prior to initiating vaccine therapy (at the leukapheresis visit), prior to
      surgery to remove the tumor, at the clinic visit prior to starting first cycle of
      temozolomide after surgery (or radiation therapy and temozolomide for those who transition to
      higher grade), at vaccine #6, and at end of vaccine treatment (1 month after vaccine #15 or
      time the subject comes off study, whichever comes first).

      Subjects will be imaged with contrast-enhanced magnetic resonance imaging (MRI) according to
      standard of care every 10 weeks (+/- 4 weeks) while on temozolomide and afterward, per the
      treating neuro-oncologist's recommendation. Revised Assessment in Neuro-Oncology (RANO)
      criteria will be used for assessment of pseudoprogression and tumor progression. Subjects
      demonstrating definitive progression will be removed from study.

      As part of standard care for these subjects, upon tumor progression, participants may undergo
      biopsy or resection. As this is not a research procedure, consent will be obtained
      separately. Subjects that have this procedure done within the Duke University Health System
      will be asked to have a portion of the tumor sample, if possible, to assess immunologic cell
      infiltration, antigen expression, and biomarkers for immunologic response.

      Please note, data collection will continue to occur outside of the defined primary and
      secondary outcomes for exploratory objectives.

      The specific exploratory objective involves describing the progression free survival (PFS)
      and overall survival (OS). The endpoint is the proportion of patients alive without disease
      progression 6 months after initial vaccine treatment, and both the median PFS, and the median
      OS.

      The objective will be reviewed at 3 years after the last subject came off study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With an Unacceptable Toxicity
time frame: Date of consent through 2 months after the last vaccination
description: The percentage of patients who experience an unacceptable toxicity defined as any Grade 3 toxicity at least possibly attributed to the vaccine (or vaccine + TMZ and/or RT) that does not resolve to baseline within 3 weeks, any Grade 3 hypersensitivity reactions requiring steroids, any Grade 4 toxicity, including neurologic events not due to progressive disease, or any life threatening-event not attributable to concomitant medication, co-morbid event, or disease progression.
measure: Percentage of Evaluable Subjects Who Had a Response Greater Than 20 Spot-forming Cells (SFC) Per 10^6 Lymphocytes
time frame: From time of pheresis #1, one day prior to first pre-surgery vaccine dose, until the time of the third post-surgery vaccination, an expected average of 24 weeks after study initiation
description: The number of spot-forming cells (SFC) per 10^6 lymphocytes measured by ELISpot. A blue-black colored precipitate forms and appears as spots at the sites of cytokine localization, with each individual spot representing an individual analyte-secreting cell.
arm group label: PEPIDH1M vaccine
arm group type: Experimental
description: PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.
intervention type: Biological
intervention name: PEPIDH1M vaccine
description: PEPIDH1M vaccine is made up of 500 µg of 25 amino acid peptide administered with 150 µg of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally. The peptide vaccine is administered in the groin area approximately 10 cm below the inguinal ligament.
arm group label: PEPIDH1M vaccine
intervention type: Biological
intervention name: Tetanus-Diphtheria Toxoid (Td)
description: After consent has been signed, all subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Within 48 hours of leukapheresis, subjects will receive a vaccine site pre-conditioning as a single dose of Td toxoid (1 flocculation unit, Lf, in a total volume of 0.4 mLs saline) administered intradermally to the right side of the groin one day prior to receiving the first PEPIDH1M vaccine.
arm group label: PEPIDH1M vaccine
other name: Tenivac
intervention type: Drug
intervention name: Temozolomide
description: Subjects are treated with temozolomide (TMZ) at a targeted dose of 50-100mg/m2/d for 21 days every 28 days for up to 12 cycles. Subjects that have transitioned to a higher grade brain tumor at time of surgery will receive TMZ and radiation therapy per standard of care before starting TMZ cycles.
arm group label: PEPIDH1M vaccine
other name: Temodar
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Katherine Peters, M.D., Ph.D.
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Gary Archer Ph.D.
investigator title: Assistant Professor Neurosurgery
mesh term: Neoplasms
mesh term: Brain Neoplasms
mesh term: Recurrence
mesh term: Temozolomide
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 