<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/NCT03299309</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00079843</org_study_id>
    <nct_id>NCT03299309</nct_id>
  </id_info>
  <brief_title>PEP-CMV in Recurrent MEdulloblastoma/Malignant Glioma</brief_title>
  <acronym>PRiME</acronym>
  <official_title>The PRiME Study: PEP-CMV in Recurrent MEdulloblastoma/Malignant Glioma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Daniel Landi</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pediatric Brain Tumor Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Annias Immunotherapeutics, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary goal of this prospective clinical trial is to evaluate the safety of PEP-CMV in&#xD;
      patients with recurrent medulloblastoma and malignant glioma. Patients with&#xD;
      histologically-proven medulloblastoma or malignant glioma who had received prior therapy for&#xD;
      their initial diagnosis and subsequently had tumor recurrence/progression may be enrolled any&#xD;
      time after recurrence/progression regardless of prior adjuvant therapy. PEP-CMV is a vaccine&#xD;
      comprised of Component A, a synthetic long peptide (SLP) of 26 amino acid residues from human&#xD;
      pp65. In May 2021, enrollment on the study was temporarily suspended due to delays in vialing&#xD;
      the PEP-CMV study vaccine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Once a patient has enrolled onto this study, prior therapy will be terminated and patients&#xD;
      will receive temozolomide 200 mg/m2/day x 5 days. If they are receiving bevacizumab at the&#xD;
      time of enrollment, they will continue bevacizumab 10 mg/Kg every 14 days.&#xD;
&#xD;
      Patients who are ≥ 18 years of age will receive a tetanus (Td) booster at the time of&#xD;
      enrollment. Immunotherapy begins with a Tetanus (Td) pre-conditioning vaccine delivered&#xD;
      intradermally (i.d.) in the right groin at the site of the vaccine injection 6-24 hours prior&#xD;
      to the first vaccine on day 21. The PEP-CMV vaccine will be administered as follows: PEP-CMV&#xD;
      Component A mixed with Montanide ISA-51 (1:1 volume ratio) intradermally administered half in&#xD;
      the RIGHT groin and half in the LEFT groin.&#xD;
&#xD;
      The first 3 PEP-CMV vaccines will occur every 2 weeks, then PEP-CMV vaccines will continue&#xD;
      monthly (+/- 2 weeks) for no more than 10 years. Blood will be obtained for immune system&#xD;
      monitoring.&#xD;
&#xD;
      In May 2021, enrollment on the study was temporarily suspended due to delays in vialing the&#xD;
      PEP-CMV study vaccine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 29, 2018</start_date>
  <completion_date type="Anticipated">April 2025</completion_date>
  <primary_completion_date type="Actual">April 27, 2023</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>Proportion of patients with unacceptable toxicity</measure>
    <time_frame>2 weeks after the 3rd PEP-CMV vaccine on the last enrolled patient</time_frame>
    <description>Evaluate the safety of PEP-CMV in pediatric patients with recurrent MB or recurrent Grade III/IV glioma</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean or median change from baseline at each follow-up assessment in ELISPOT (IFN-γ)</measure>
    <time_frame>24 months</time_frame>
    <description>Quantitate the immune response to the components of the PEP-CMV vaccine by ELISPOT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean or median change from baseline at each follow-up assessment in ELISA (gB-KLH)</measure>
    <time_frame>24 months</time_frame>
    <description>Quantitate the immune response to the components of the PEP-CMV vaccine by ELISA</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Recurrent Medulloblastoma</condition>
  <condition>Recurrent Brain Tumor, Childhood</condition>
  <condition>Malignant Glioma</condition>
  <arm_group>
    <arm_group_label>PEP-CMV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cytomegalovirus (CMV)-specific peptide vaccine (PEP-CMV)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PEP-CMV</intervention_name>
    <description>Patients receive temozolomide (TMZ) 200 mg/m2/day x 5 days. On day 20, patients will receive a Tetanus-diphtheria pre-conditioning vaccination with Td (tetanus, diphtheria toxoid, adsorbed). Immunotherapy begins the following day, on day 21, with injection of the PEP-CMV vaccine as follows: PEP-CMV Component A mixed with Montanide ISA-51 intradermally administered half in the RIGHT groin and half in the LEFT groin.</description>
    <arm_group_label>PEP-CMV</arm_group_label>
    <other_name>PEP-CMV vaccine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients who are 3 - 35 years old&#xD;
&#xD;
          2. Histopathologically proven previous diagnosis of medulloblastoma or Grade III or IV&#xD;
             glioma.&#xD;
&#xD;
          3. Radiology evidence of recurrent medulloblastoma (reMB) or recurrent Grade III and IV&#xD;
             glioma. Patients will be considered for a biopsy or resection of the&#xD;
             recurrent/progressive tumor at the discretion of the treating neurosurgeon and&#xD;
             neuro-oncologist.&#xD;
&#xD;
          4. Brain MRI within one month prior to enrollment.&#xD;
&#xD;
          5. Received prior therapy for their initial diagnosis prior to recurrence/progression or&#xD;
             who are unable to receive radiation therapy due to genetic disorders that put them at&#xD;
             significant risk for radiation-induced secondary malignancies (i.e. Gorlin's syndrome&#xD;
             or NF1 mutation).&#xD;
&#xD;
          6. Patients with neurological deficits should have deficits that are stable for a minimum&#xD;
             of 2 weeks prior to registration.&#xD;
&#xD;
          7. Karnofsky Performance Status (KPS) of ≥ 60% (KPS for &gt; 10 years of age) or Lansky&#xD;
             performance Score (LPS) of ≥ 60 (LPS for ≤ 10 years of age) assessed within 2 weeks&#xD;
             prior to registration. Patients who are unable to walk because of paralysis but who&#xD;
             are up in a wheel chair will be considered ambulatory for the purposes of the&#xD;
             performance score.&#xD;
&#xD;
          8. Bone Marrow:&#xD;
&#xD;
               -  ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported)*.&#xD;
&#xD;
               -  Platelets ≥ 100,000/µl (unsupported)*.&#xD;
&#xD;
               -  Hemoglobin &gt; 8 g/dL (may be supported).&#xD;
&#xD;
          9. Renal:&#xD;
&#xD;
             • Serum creatinine ≤ upper limit of institutional normal.&#xD;
&#xD;
         10. Hepatic:&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 times upper limit of normal for age.&#xD;
&#xD;
               -  SGPT (ALT) ≤ 3 times institutional upper limit of normal for age.&#xD;
&#xD;
               -  SGOT (AST) ≤ 3 times institutional upper limit of normal for age.&#xD;
&#xD;
         11. Patients of childbearing or child-fathering potential must be willing to use a&#xD;
             medically acceptable form of birth control, which includes abstinence, while being&#xD;
             treated on this study.&#xD;
&#xD;
         12. Signed informed consent according to institutional guidelines must be obtained prior&#xD;
             to registration.&#xD;
&#xD;
         13. Any prior chemoradiotherapy is allowed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or need to breast feed during the study period (Negative serum pregnancy test&#xD;
             required).&#xD;
&#xD;
          2. Active infection requiring treatment or an unexplained febrile (&gt; 101.5 degrees F)&#xD;
             illness.&#xD;
&#xD;
          3. Known immunosuppressive disease or human immunodeficiency virus infection.&#xD;
&#xD;
          4. Patients with active renal, cardiac (congestive cardiac failure, myocardial&#xD;
             infarction, myocarditis), or pulmonary disease.&#xD;
&#xD;
          5. Patients receiving concomitant immunosuppressive agents for medical condition.&#xD;
&#xD;
          6. Patients who need definitive radiotherapy for treatment of recurrent MB or recurrent&#xD;
             Grade III or IV glioma.&#xD;
&#xD;
          7. Patients receiving any other investigational drug therapy.&#xD;
&#xD;
          8. Patients on corticosteroids &gt; 0.1 mg/Kg/day (i.e. &gt; the maximum dose of 4 mg/day).&#xD;
&#xD;
          9. Patients with any clinically significant unrelated systemic illness (serious&#xD;
             infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).&#xD;
&#xD;
         10. Patients with inability to return for follow-up visits or obtain follow-up studies&#xD;
             required to assess toxicity to therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel Landi, MD</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>
  <link>
    <url>https://tischbraintumorcenter.duke.edu/</url>
    <description>The Preston Robert Tisch Brain Tumor Center at Duke</description>
  </link>
  <link>
    <url>http://www.dukecancerinstitute.org/</url>
    <description>Duke Cancer Institute</description>
  </link>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>May 17, 2023</last_update_submitted>
  <last_update_submitted_qc>May 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Daniel Landi</investigator_full_name>
    <investigator_title>Assistant Professor of Pediatrics and Neurosurgery</investigator_title>
  </responsible_party>
  <keyword>Glioma</keyword>
  <keyword>Medulloblastoma</keyword>
  <keyword>PRiME</keyword>
  <keyword>Pro00079843</keyword>
  <keyword>Thompson</keyword>
  <keyword>Pediatric</keyword>
  <keyword>Landi</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Medulloblastoma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03299309
org study id: Pro00079843
nct id: NCT03299309
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary goal of this prospective clinical trial is to evaluate the safety of PEP-CMV in
      patients with recurrent medulloblastoma and malignant glioma. Patients with
      histologically-proven medulloblastoma or malignant glioma who had received prior therapy for
      their initial diagnosis and subsequently had tumor recurrence/progression may be enrolled any
      time after recurrence/progression regardless of prior adjuvant therapy. PEP-CMV is a vaccine
      comprised of Component A, a synthetic long peptide (SLP) of 26 amino acid residues from human
      pp65. In May 2021, enrollment on the study was temporarily suspended due to delays in vialing
      the PEP-CMV study vaccine.
Once a patient has enrolled onto this study, prior therapy will be terminated and patients
      will receive temozolomide 200 mg/m2/day x 5 days. If they are receiving bevacizumab at the
      time of enrollment, they will continue bevacizumab 10 mg/Kg every 14 days.

      Patients who are ≥ 18 years of age will receive a tetanus (Td) booster at the time of
      enrollment. Immunotherapy begins with a Tetanus (Td) pre-conditioning vaccine delivered
      intradermally (i.d.) in the right groin at the site of the vaccine injection 6-24 hours prior
      to the first vaccine on day 21. The PEP-CMV vaccine will be administered as follows: PEP-CMV
      Component A mixed with Montanide ISA-51 (1:1 volume ratio) intradermally administered half in
      the RIGHT groin and half in the LEFT groin.

      The first 3 PEP-CMV vaccines will occur every 2 weeks, then PEP-CMV vaccines will continue
      monthly (+/- 2 weeks) for no more than 10 years. Blood will be obtained for immune system
      monitoring.

      In May 2021, enrollment on the study was temporarily suspended due to delays in vialing the
      PEP-CMV study vaccine.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients with unacceptable toxicity
time frame: 2 weeks after the 3rd PEP-CMV vaccine on the last enrolled patient
description: Evaluate the safety of PEP-CMV in pediatric patients with recurrent MB or recurrent Grade III/IV glioma
measure: Mean or median change from baseline at each follow-up assessment in ELISPOT (IFN-γ)
time frame: 24 months
description: Quantitate the immune response to the components of the PEP-CMV vaccine by ELISPOT
measure: Mean or median change from baseline at each follow-up assessment in ELISA (gB-KLH)
time frame: 24 months
description: Quantitate the immune response to the components of the PEP-CMV vaccine by ELISA
arm group label: PEP-CMV
arm group type: Experimental
description: Cytomegalovirus (CMV)-specific peptide vaccine (PEP-CMV)
intervention type: Drug
intervention name: PEP-CMV
description: Patients receive temozolomide (TMZ) 200 mg/m2/day x 5 days. On day 20, patients will receive a Tetanus-diphtheria pre-conditioning vaccination with Td (tetanus, diphtheria toxoid, adsorbed). Immunotherapy begins the following day, on day 21, with injection of the PEP-CMV vaccine as follows: PEP-CMV Component A mixed with Montanide ISA-51 intradermally administered half in the RIGHT groin and half in the LEFT groin.
arm group label: PEP-CMV
other name: PEP-CMV vaccine
criteria: 
gender: All
minimum age: 3 Years
maximum age: 35 Years
healthy volunteers: No
last name: Daniel Landi, MD
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
url: https://tischbraintumorcenter.duke.edu/
description: The Preston Robert Tisch Brain Tumor Center at Duke
url: http://www.dukecancerinstitute.org/
description: Duke Cancer Institute
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Daniel Landi
investigator title: Assistant Professor of Pediatrics and Neurosurgery
mesh term: Glioma
mesh term: Brain Neoplasms
mesh term: Medulloblastoma
mesh term: Recurrence
mesh term: Vaccines
sharing ipd: No