<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/NCT02993315</url>
  </required_header>
  <id_info>
    <org_study_id>NL55823.000.15</org_study_id>
    <nct_id>NCT02993315</nct_id>
  </id_info>
  <brief_title>Melanoma Patients Immunized With Natural DenDritic Cells</brief_title>
  <acronym>MIND-DC</acronym>
  <official_title>A Randomized, Double--Blind, Placebo-Controlled Phase III Study to Evaluate Active Immunization in Adjuvant Therapy of Patients With Stage IIIB and IIIC Melanoma With Natural Dendritic Cells Pulsed With Synthetic Peptides.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dutch National Health Care Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>ZonMw: The Netherlands Organisation for Health Research and Development</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to determine whether adjuvant treatment with nDC vaccination, after&#xD;
      complete radical lymph node dissection or sentinel node procedure in stage IIIB and IIIC&#xD;
      melanoma patients, improves recurrence-free survival (RFS) as compared to treatment with&#xD;
      matching placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 3, randomized, double-blind, interventional study of nDC vaccination versus&#xD;
      placebo. Dendritic cell-based immunotherapy consists of antigen-loaded autologous DC that are&#xD;
      administered to patients with the intention of inducing antigen-specific T and B cell&#xD;
      responses and proved safe with minimal side effects. Natural DC (nDC) consist of plasmacytoid&#xD;
      DC and myeloid DC. Subjects will be randomized 2:1 and stratified by stage of disease,&#xD;
      adjuvant radiotherapy, BRAF mutation status, HLA-type and nDC production centre. The&#xD;
      treatment will be continued for a maximum of 1.5 years or until recurrence of disease,&#xD;
      unacceptable toxicity or withdrawal from the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recurrence-free survival rate</measure>
    <time_frame>2 years</time_frame>
    <description>The primary objective of this study is to determine whether adjuvant nDC vaccination, after complete radical lymph node dissection or sentinel node procedure in stage IIIB and IIIC melanoma patients, improves 2-year RFS rate as compared to treatment with matching placebo. Defined as the percentage of patients who are alive and without recurrence of melanoma 2 years after randomization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recurrence-free survival</measure>
    <time_frame>2 years and 5 years</time_frame>
    <description>Median RFS duration will be assessed by physical examination and CT of the chest and abdomen every 3-12 months, or on clinical indication, during 5 years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>2-years and median</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor specific T-cell response</measure>
    <time_frame>week 1, week 9, week 10, week 31, week 39, week 57, week 65, week 78, month 24, month 60</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Questionnaires</measure>
    <time_frame>baseline, week 14, week 26, month 12, month 24, month 36, month 60</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Costs (direct and indirect) of treatment</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QALY</measure>
    <time_frame>2 years</time_frame>
    <description>A cost-effectiveness acceptability curve will be derived that is able to evaluate efficiency by using different tresholds (willingness to pay) for a QALY.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events related to treatment</measure>
    <time_frame>1,5 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">210</enrollment>
  <condition>Melanoma (Skin)</condition>
  <arm_group>
    <arm_group_label>nDC vaccination arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in the nDC vaccination arm will receive a maximum of 3 cycles each consisting of 3 nDC injections intranodally (3-8x10^6 nDC).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will receive a maximum of 3 cycles each consisting of 3 placebo injections intranodally.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>nDC vaccination</intervention_name>
    <arm_group_label>nDC vaccination arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>placebo injection</intervention_name>
    <arm_group_label>placebo arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Eligibility Criteria:&#xD;
&#xD;
          -  at least 18 years of age.&#xD;
&#xD;
          -  Histologically confirmed stage III cutaneous melanoma, classified as IIIB or IIIC&#xD;
             disease (AJCC 2009). Patients with completely resected in-transit and/or satellite&#xD;
             metastases and patients with unknown primary melanoma are allowed in this trial.&#xD;
&#xD;
          -  Radical lymph node dissection involved site with complete resection or sentinel node&#xD;
             procedure (in case of patients without RLND because of limited sentinel-node positive&#xD;
             disease) of melanoma as documented on the operating report and pathology report with&#xD;
             at least the minimal levels excised as stated in national guidelines.&#xD;
&#xD;
          -  Radical lymph node dissection involved site with complete resection or sentinel node&#xD;
             procedure (in case of patients without RLND because of limited sentinel-node positive&#xD;
             disease) must be performed within 12 weeks prior to start of study.&#xD;
&#xD;
          -  Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling&#xD;
             drains).&#xD;
&#xD;
          -  Absence of distant metastases must be documented by a CT scan of the chest and abdomen&#xD;
             (including pelvis) or a Positron Emission Tomography (PET) scan, the scan should have&#xD;
             been performed within 6 weeks before surgery or after surgery prior to inclusion. In&#xD;
             addition, a physical exam after surgery must be performed also excluding distant&#xD;
             metastases.&#xD;
&#xD;
          -  No clinical evidence for brain metastasis. If brain metastases are clinically&#xD;
             suspected, a CT or Magnetic Resonance Imaging (MRI) scan of the brain must exclude&#xD;
             brain metastases.&#xD;
&#xD;
          -  World Health Organization (WHO) performance status of 0 or 1 at time of randomization.&#xD;
&#xD;
          -  Adequate hematologic, renal and liver function as defined by laboratory values&#xD;
             performed within 4 weeks of randomization.&#xD;
&#xD;
          -  No second malignancy in the previous 5 years, with the exception of adequately treated&#xD;
             carcinoma in-situ and basal or squamous cell carcinoma of the skin.&#xD;
&#xD;
          -  No concomitant use of immunosuppressive drugs orally or intravenously. Topical and&#xD;
             intranasal steroids are permitted.&#xD;
&#xD;
          -  No uncontrolled infectious disease, i.e. negative testing for HIV, HBV, HCV and&#xD;
             syphilis.&#xD;
&#xD;
          -  No autoimmune disease such as, but not limited to, inflammatory bowel disease,&#xD;
             multiple sclerosis, and lupus. Patients with type 1 diabetes mellitus, hypothyroidism&#xD;
             after autoimmune thyroiditis and skin disorders are not excluded.&#xD;
&#xD;
          -  No serious (bleeding and clotting) condition that may interfere with safe&#xD;
             leukapheresis.&#xD;
&#xD;
          -  No pregnant or lactating women.&#xD;
&#xD;
          -  No Women Of Child-Bearing Potential (WOCBP) who are unwilling or unable to use an&#xD;
             acceptable method to avoid pregnancy for up to 8 weeks after the last administration&#xD;
             of the treatment. WOCBP include any female who has experienced menarche and who has&#xD;
             not undergone successful surgical sterilization (hysterectomy, bilateral tubal&#xD;
             ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea &gt;&#xD;
             12 consecutive months].&#xD;
&#xD;
          -  Patients must have absence of any psychological, familial, sociological or&#xD;
             geographical condition potentially hampering compliance with the study protocol and&#xD;
             follow-up schedule; those conditions must be discussed with the patient before&#xD;
             registration in the trial.&#xD;
&#xD;
          -  Expected adequacy of follow-up.&#xD;
&#xD;
          -  Written informed consent.&#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>Jolanda de Vries, Prof. dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NKI-AvL</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VUmc</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ErasmusMC</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isala klinieken</name>
      <address>
        <city>Zwolle</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>March 11, 2021</last_update_submitted>
  <last_update_submitted_qc>March 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2021</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>Melanoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02993315
org study id: NL55823.000.15
nct id: NCT02993315
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The aim of this study is to determine whether adjuvant treatment with nDC vaccination, after
      complete radical lymph node dissection or sentinel node procedure in stage IIIB and IIIC
      melanoma patients, improves recurrence-free survival (RFS) as compared to treatment with
      matching placebo.
This is a phase 3, randomized, double-blind, interventional study of nDC vaccination versus
      placebo. Dendritic cell-based immunotherapy consists of antigen-loaded autologous DC that are
      administered to patients with the intention of inducing antigen-specific T and B cell
      responses and proved safe with minimal side effects. Natural DC (nDC) consist of plasmacytoid
      DC and myeloid DC. Subjects will be randomized 2:1 and stratified by stage of disease,
      adjuvant radiotherapy, BRAF mutation status, HLA-type and nDC production centre. The
      treatment will be continued for a maximum of 1.5 years or until recurrence of disease,
      unacceptable toxicity or withdrawal from the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Recurrence-free survival rate
time frame: 2 years
description: The primary objective of this study is to determine whether adjuvant nDC vaccination, after complete radical lymph node dissection or sentinel node procedure in stage IIIB and IIIC melanoma patients, improves 2-year RFS rate as compared to treatment with matching placebo. Defined as the percentage of patients who are alive and without recurrence of melanoma 2 years after randomization.
measure: Recurrence-free survival
time frame: 2 years and 5 years
description: Median RFS duration will be assessed by physical examination and CT of the chest and abdomen every 3-12 months, or on clinical indication, during 5 years.
measure: Overall survival
time frame: 2-years and median
measure: Tumor specific T-cell response
time frame: week 1, week 9, week 10, week 31, week 39, week 57, week 65, week 78, month 24, month 60
measure: Quality of Life Questionnaires
time frame: baseline, week 14, week 26, month 12, month 24, month 36, month 60
measure: Costs (direct and indirect) of treatment
time frame: 2 years
measure: QALY
time frame: 2 years
description: A cost-effectiveness acceptability curve will be derived that is able to evaluate efficiency by using different tresholds (willingness to pay) for a QALY.
measure: Adverse Events related to treatment
time frame: 1,5 year
arm group label: nDC vaccination arm
arm group type: Experimental
description: Patients in the nDC vaccination arm will receive a maximum of 3 cycles each consisting of 3 nDC injections intranodally (3-8x10^6 nDC).
arm group label: placebo arm
arm group type: Placebo Comparator
description: Patients will receive a maximum of 3 cycles each consisting of 3 placebo injections intranodally.
intervention type: Biological
intervention name: nDC vaccination
arm group label: nDC vaccination arm
intervention type: Biological
intervention name: placebo injection
arm group label: placebo arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jolanda de Vries, Prof. dr.
role: Principal Investigator
affiliation: Radboud University Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Melanoma
sharing ipd: Undecided