<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/NCT03282617</url>
  </required_header>
  <id_info>
    <org_study_id>NP01/03/16</org_study_id>
    <nct_id>NCT03282617</nct_id>
  </id_info>
  <brief_title>Dendritic Cell Therapy With CD137L-DC-EBV-VAX in Locally Advanced Stage IV or Locally Recurrent/Metastatic Nasopharyngeal Carcinoma</brief_title>
  <official_title>Dendritic Cell Therapy With CD137L-DC-EBV-VAX in Locally Advanced Stage IV or Locally Recurrent/Metastatic Nasopharyngeal Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National University Hospital, Singapore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National University Hospital, Singapore</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is carried out to find out the safety and recommended dose of CD137L-DC-EBV-VAX in&#xD;
      nasopharyngeal cancer. CD137L-DC-EBV-VAX is a product made from one of our own immune system&#xD;
      cells (dendritic cell, DC). Dendritic cells are immune cells that help to stimulate our&#xD;
      body's T lymphocytes to fight cancer by presenting specific proteins from the cancer cells.&#xD;
      The investigators have developed in the laboratory a highly effective dendritic cell which is&#xD;
      primed to activate T cells with the Epstein-Barr virus (EBV) proteins. It is hoped that this&#xD;
      will stir an immune response to recognize NPC cells and kill them as part of body's immune&#xD;
      surveillance system.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will involve two cohorts of patients, A and B. Patients are invited because they&#xD;
      have either (A) locally recurrent or metastatic nasopharyngeal cancer; or (B) stage 4 locally&#xD;
      advanced nasopharyngeal cancer (N2 or N3 disease and/or T4) and is known to be associated&#xD;
      with a high risk of distant relapse.&#xD;
&#xD;
      This study is carried out to find out the safety and recommended dose of CD137L-DC-EBV-VAX in&#xD;
      nasopharyngeal cancer. CD137L-DC-EBV-VAX is a product made from one of our own immune system&#xD;
      cells (dendritic cell, DC). Dendritic cells are immune cells that help to stimulate our&#xD;
      body's T lymphocytes to fight cancer by presenting specific proteins from the cancer cells.&#xD;
      The investigators have developed in the laboratory a highly effective dendritic cell which is&#xD;
      primed to activate T cells with the Epstein-Barr virus (EBV) proteins. It is hoped that this&#xD;
      will stir an immune response to recognize NPC cells and kill them as part of body's immune&#xD;
      surveillance system.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 14, 2017</start_date>
  <completion_date type="Anticipated">August 14, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 14, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients will be given CD137L-DC-EBV-VAX for about 5 - 7 times and be followed up until a maximum of 3 years from study entry.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability and recommended dose of CD137L-DC-EBV-VAX</measure>
    <time_frame>From the start of assessment until study completion, an average of 3 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Activation of EBV-specific T cell responses</measure>
    <time_frame>From the start of assessment until study completion, an average of 3 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antitumor Effect based on Immune Response Criteria (IRC)</measure>
    <time_frame>From the start of assessment until study completion, an average of 3 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival and overall survival</measure>
    <time_frame>From the start of assessment until study completion, an average of 3 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">55</enrollment>
  <condition>Nasopharyngeal Cancer</condition>
  <arm_group>
    <arm_group_label>locally recurrent or metastatic nasopharyngeal cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This cohort consists of patients with metastatic or locally recurrent NPC who have received systemic concurrent chemotherapy and have a favourable response of stable disease, partial or complete response. As up to 30% of these patients will suffer from relapse within 5 months of completion of chemotherapy, following definitive treatment, y, and treatment with CD137L-DC-EBV-VAX may activate T cell response against the tumor and prolong time to progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>stage 4 locally advanced nasopharyngeal cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This cohort consists of patients with stage 4 locally advanced patients (N2 and N3 disease, and/or T4 disease) who are treated definitely with chemoradiation with curative intent, but who have a high risk of distant relapse. Treatment with CD137L-DC-EBV-VAX may activate antitumor T cell responses and prolong time to relapse.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CD137L-DC-EBV-VAX</intervention_name>
    <description>Patients will receive CD137L-DC-EBV-VAX at a dose of approximately 5-50 millioncells every 2 weeks, for a total of 5-7 times.</description>
    <arm_group_label>locally recurrent or metastatic nasopharyngeal cancer</arm_group_label>
    <arm_group_label>stage 4 locally advanced nasopharyngeal cancer</arm_group_label>
    <other_name>Dendritic cell therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Eligibility Criteria:&#xD;
&#xD;
          -  Age ≥ 18 year&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
          -  2 cohorts of patients are eligible for the study: Cohort A - Histologically or&#xD;
             cytologically confirmed non-keratinizing nasopharyngeal carcinoma (NPC) that has&#xD;
             recurred at locoregional and/or distant sites. Patients must have just received at&#xD;
             least 1 cycle of chemotherapy and achieved stable disease, partial or complete&#xD;
             response.&#xD;
&#xD;
        Cohort B - Histologically or cytologically confirmed stage 4A/B (locally advanced)&#xD;
        non-keratinizing NPC that has just completed concurrent chemoradiotherapy less than 2&#xD;
        months before study entry.&#xD;
&#xD;
          -  Measurable disease according to the RECIST criteria (version 1.1) is not necessary,&#xD;
             but tumor assessments on follow up will be according to RECIST criteria (version 1.1)&#xD;
             as defined in section 11 for the evaluation of disease.&#xD;
&#xD;
          -  Archived or fresh tumor sample available. Willingness to donate blood and tissue for&#xD;
             mandatory correlative research studies (see Section 9).&#xD;
&#xD;
          -  ECOG performance status of 0, 1 or 2 (see Appendix A).&#xD;
&#xD;
          -  Patients must have adequate organ and marrow function as defined below:&#xD;
&#xD;
               -  Absolute monocyte count ≥0.2 x 109/L&#xD;
&#xD;
               -  Platelets ≥100 x109/L&#xD;
&#xD;
               -  Hemoglobin ≥8.0 g/dL&#xD;
&#xD;
               -  Serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase,&#xD;
                  [SGPT]) &lt; 2.5 x upper limit of normal (ULN), OR &lt; 5 x ULN in the presence of&#xD;
                  liver metastases.&#xD;
&#xD;
               -  Serum total bilirubin &lt; 2 x ULN (except patients with Gilbert Syndrome, who can&#xD;
                  have total bilirubin &lt;3.0 mg/dL)&#xD;
&#xD;
               -  Serum creatinine &lt; 1.5 x ULN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Any of the following:&#xD;
&#xD;
          -  Chemotherapy ≤ 4 weeks prior to CD137L-DC-EBV-VAX study treatment.&#xD;
&#xD;
          -  Radiotherapy ≤ 4 weeks prior to CD137L-DC-EBV-VAX study treatment.&#xD;
&#xD;
          -  Nitrosoureas or Mitomycin C ≤ 4 weeks prior to registration&#xD;
&#xD;
        NOTE: Prior palliative radiotherapy to bone metastases is allowed ≤ 4 weeks prior to&#xD;
        registration. Prior immunotherapy with immune checkpoint inhibitors will not be allowed.&#xD;
&#xD;
          -  Prior investigational agents ≤ 4 weeks prior to registration.&#xD;
&#xD;
          -  Known allergy to Tetanus and/or Diphtheria toxoid.&#xD;
&#xD;
          -  Known brain metastases or leptomeningeal metastases. NOTE: symptomatic, and/or if they&#xD;
             require immunosuppressive doses of corticosteroids (e.g. &gt;10 mg/day prednisone or&#xD;
             equivalents) for at least 2 weeks prior to study drug administration. Patients with&#xD;
             treated brain metastases who are deemed clinically stable and without radiological&#xD;
             progression on PET, MRI or CT scan performed ≤ 8 weeks of study entry, are not&#xD;
             excluded. NOTE: Primary nasopharyngeal cancers that directly invade the skull base and&#xD;
             extend into the infratemporal fossa(e) are not regarded as brain metastases and are&#xD;
             not excluded.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Any of the following:&#xD;
&#xD;
               -  Pregnant women&#xD;
&#xD;
               -  Nursing women&#xD;
&#xD;
               -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
                  contraception&#xD;
&#xD;
          -  Active autoimmune disease or history of autoimmune disease that might recur, which may&#xD;
             affect vital organ function or require immune suppressive treatment including systemic&#xD;
             corticosteroids. NOTE: These include but are not limited to patients with a history of&#xD;
             immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating)&#xD;
             neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease&#xD;
             such as SLE, connective tissue diseases, scleroderma, inflammatory bowel disease&#xD;
             (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic&#xD;
             epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should&#xD;
             be excluded because of the risk of recurrence or exacerbation of disease. Patients&#xD;
             with vitiligo, endocrine deficiencies including thyroiditis managed with replacement&#xD;
             hormones including physiologic corticosteroids are eligible. Patients with rheumatoid&#xD;
             arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with&#xD;
             topical medication and patients with positive serology, such as antinuclear antibodies&#xD;
             (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ&#xD;
             involvement and potential need for systemic treatment but should otherwise be&#xD;
             eligible.&#xD;
&#xD;
          -  Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus,&#xD;
             residual hypothyroidism due to autoimmune condition only requiring hormone&#xD;
             replacement, psoriasis not requiring systemic treatment, or conditions not expected to&#xD;
             recur in the absence of an external trigger (precipitating event).&#xD;
&#xD;
          -  Condition requiring systemic treatment with either corticosteroids (&gt;10 mg daily&#xD;
             prednisone equivalents) or other immunosuppressive medications within 14 days of study&#xD;
             drug administration. Inhaled or topical steroids and adrenal replacement doses &lt;10 mg&#xD;
             daily prednisone equivalents are permitted in the absence of active autoimmune&#xD;
             disease. Patients are permitted to use topical, ocular, intra-articular, intranasal,&#xD;
             and inhalational corticosteroids (with minimal systemic absorption). Physiologic&#xD;
             replacement doses of systemic corticosteroids are permitted, even if &lt;10 mg/day&#xD;
             prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g.,&#xD;
             contrast dye allergy) or for treatment of non-autoimmune conditions (e.g.,&#xD;
             delayed-type hypersensitivity reaction caused by contact allergen) is permitted.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boon Cher Goh</last_name>
    <role>Principal Investigator</role>
    <affiliation>National University Hospital, Singapore</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Boon Cher Goh</last_name>
    <phone>(65) 6779 5555</phone>
    <email>phcgbc@nus.edu.sg</email>
  </overall_contact>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boon Cher Goh, MBBS, MRCP</last_name>
      <phone>65-6772-4617</phone>
      <email>Boon_Cher_Goh@nuhs.com.sg</email>
    </contact>
    <investigator>
      <last_name>Boon Cher Goh, MBBS, MRCP</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Petersson F. Nasopharyngeal carcinoma: a review. Semin Diagn Pathol. 2015 Jan;32(1):54-73. doi: 10.1053/j.semdp.2015.02.021. Epub 2015 Feb 25.</citation>
    <PMID>25769204</PMID>
  </reference>
  <reference>
    <citation>Lee AW, Ma BB, Ng WT, Chan AT. Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective. J Clin Oncol. 2015 Oct 10;33(29):3356-64. doi: 10.1200/JCO.2015.60.9347. Epub 2015 Sep 8.</citation>
    <PMID>26351355</PMID>
  </reference>
  <reference>
    <citation>Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002 Dec;12(6):421-9. doi: 10.1016/s1044579x02000858.</citation>
    <PMID>12450728</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>September 12, 2017</last_update_submitted>
  <last_update_submitted_qc>September 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nasopharyngeal Carcinoma</mesh_term>
    <mesh_term>Nasopharyngeal Neoplasms</mesh_term>
  </condition_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/NCT03282617
org study id: NP01/03/16
nct id: NCT03282617
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is carried out to find out the safety and recommended dose of CD137L-DC-EBV-VAX in
      nasopharyngeal cancer. CD137L-DC-EBV-VAX is a product made from one of our own immune system
      cells (dendritic cell, DC). Dendritic cells are immune cells that help to stimulate our
      body's T lymphocytes to fight cancer by presenting specific proteins from the cancer cells.
      The investigators have developed in the laboratory a highly effective dendritic cell which is
      primed to activate T cells with the Epstein-Barr virus (EBV) proteins. It is hoped that this
      will stir an immune response to recognize NPC cells and kill them as part of body's immune
      surveillance system.
This study will involve two cohorts of patients, A and B. Patients are invited because they
      have either (A) locally recurrent or metastatic nasopharyngeal cancer; or (B) stage 4 locally
      advanced nasopharyngeal cancer (N2 or N3 disease and/or T4) and is known to be associated
      with a high risk of distant relapse.

      This study is carried out to find out the safety and recommended dose of CD137L-DC-EBV-VAX in
      nasopharyngeal cancer. CD137L-DC-EBV-VAX is a product made from one of our own immune system
      cells (dendritic cell, DC). Dendritic cells are immune cells that help to stimulate our
      body's T lymphocytes to fight cancer by presenting specific proteins from the cancer cells.
      The investigators have developed in the laboratory a highly effective dendritic cell which is
      primed to activate T cells with the Epstein-Barr virus (EBV) proteins. It is hoped that this
      will stir an immune response to recognize NPC cells and kill them as part of body's immune
      surveillance system.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be given CD137L-DC-EBV-VAX for about 5 - 7 times and be followed up until a maximum of 3 years from study entry.
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability and recommended dose of CD137L-DC-EBV-VAX
time frame: From the start of assessment until study completion, an average of 3 year
measure: Activation of EBV-specific T cell responses
time frame: From the start of assessment until study completion, an average of 3 year
measure: Antitumor Effect based on Immune Response Criteria (IRC)
time frame: From the start of assessment until study completion, an average of 3 year
measure: Progression-free survival and overall survival
time frame: From the start of assessment until study completion, an average of 3 year
arm group label: locally recurrent or metastatic nasopharyngeal cancer
arm group type: Experimental
description: This cohort consists of patients with metastatic or locally recurrent NPC who have received systemic concurrent chemotherapy and have a favourable response of stable disease, partial or complete response. As up to 30% of these patients will suffer from relapse within 5 months of completion of chemotherapy, following definitive treatment, y, and treatment with CD137L-DC-EBV-VAX may activate T cell response against the tumor and prolong time to progression.
arm group label: stage 4 locally advanced nasopharyngeal cancer
arm group type: Experimental
description: This cohort consists of patients with stage 4 locally advanced patients (N2 and N3 disease, and/or T4 disease) who are treated definitely with chemoradiation with curative intent, but who have a high risk of distant relapse. Treatment with CD137L-DC-EBV-VAX may activate antitumor T cell responses and prolong time to relapse.
intervention type: Biological
intervention name: CD137L-DC-EBV-VAX
description: Patients will receive CD137L-DC-EBV-VAX at a dose of approximately 5-50 millioncells every 2 weeks, for a total of 5-7 times.
arm group label: locally recurrent or metastatic nasopharyngeal cancer
arm group label: stage 4 locally advanced nasopharyngeal cancer
other name: Dendritic cell therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Boon Cher Goh
role: Principal Investigator
affiliation: National University Hospital, Singapore
last name: Boon Cher Goh
phone: (65) 6779 5555
email: phcgbc@nus.edu.sg
facility: 
status: Recruiting
contact: 
investigator: 
country: Singapore
citation: Petersson F. Nasopharyngeal carcinoma: a review. Semin Diagn Pathol. 2015 Jan;32(1):54-73. doi: 10.1053/j.semdp.2015.02.021. Epub 2015 Feb 25.
PMID: 25769204
citation: Lee AW, Ma BB, Ng WT, Chan AT. Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective. J Clin Oncol. 2015 Oct 10;33(29):3356-64. doi: 10.1200/JCO.2015.60.9347. Epub 2015 Sep 8.
PMID: 26351355
citation: Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002 Dec;12(6):421-9. doi: 10.1016/s1044579x02000858.
PMID: 12450728
responsible party type: Sponsor
mesh term: Nasopharyngeal Carcinoma
mesh term: Nasopharyngeal Neoplasms
sharing ipd: No