<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/NCT02203864</url>
  </required_header>
  <id_info>
    <org_study_id>1155.2</org_study_id>
    <nct_id>NCT02203864</nct_id>
  </id_info>
  <brief_title>Dose Escalation Study to Evaluate Safety and Tolerability of an Allogeneic Tumor Vaccine BIWB 2 in Patients With Advanced Malignant Melanoma</brief_title>
  <official_title>An Open-label, Multicenter, Controlled, Combined Parallel Group and Dose Escalation (0, 0.12, 1.2, 12.0 µg IL-2/10**8 Cells/24 Hours) Study, to Evaluate the Safety and Tolerability of an Allogeneic Tumor Vaccine BIWB 2 Containing Melanoma Cells Transfected With the Human IL-2 Gene in Patients With Advanced Malignant Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Evaluation of safety and tolerability of four intradermal injections given at two week&#xD;
      intervals. In addition the efficacy of transferrinfection was determined by quantifying&#xD;
      Interleukin 2 (IL-2), which was locally produced by the implanted, transfected allogenic&#xD;
      melanoma cells at the injection sites. Further determination of tumor specific and clinical&#xD;
      host responses induced or augmented by the treatment were determined.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 1998</start_date>
  <primary_completion_date type="Actual">February 2001</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of dose limiting toxicity (DLT)</measure>
    <time_frame>up to 6 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 28 days after the last vaccination</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Grading of local reactions on a 4-point-scale</measure>
    <time_frame>up to 28 days after the last vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with IL-2 transcripts in biopsies of injection sites</measure>
    <time_frame>4-6 and 48 hours after first vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with delayed type hypersensitivity skin reaction</measure>
    <time_frame>up to 28 days after the last vaccination</time_frame>
    <description>delayed type hypersensitivity testing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of antigen-positive cells in biopsies from metastatic lesions</measure>
    <time_frame>up to 28 days after the last vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of antigen-positive cells in the cellular infiltrate at the vaccination site</measure>
    <time_frame>up to 28 days after the last vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with a positive reaction to Multitest Merieux</measure>
    <time_frame>up to day 14</time_frame>
    <description>positive reaction: sum of all indurations of all existing reactions =&gt; 10 mm (male) or &gt;= 5 mm (female)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in T cell proliferation as ratio of post-vaccination to pre-vaccination</measure>
    <time_frame>up to 28 days after the last vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in S-100 beta protein level in serum</measure>
    <time_frame>up to 28 days after the last vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinical response</measure>
    <time_frame>up to 28 days after the last vaccination</time_frame>
    <description>clinical response = complete and partial response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in interferon-gamma secretion as ratio of post-vaccination to pre-vaccination</measure>
    <time_frame>up to 28 days after the last vaccination</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>BIBW2 with IL-2 secreting cell line</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BIBW2 without IL-2 secreting cell line</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BIBW2 component A</intervention_name>
    <description>BIBW2 without IL-2 secreting cell line</description>
    <arm_group_label>BIBW2 without IL-2 secreting cell line</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BIBW2 component B</intervention_name>
    <description>BIBW2 with IL-2 secreting cell line</description>
    <arm_group_label>BIBW2 with IL-2 secreting cell line</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who fail to respond to conventional therapy or for whom conventional therapy&#xD;
             is not available&#xD;
&#xD;
          -  Metastatic melanoma (stage IV AJCC) which is surgically or medically incurable because&#xD;
             of distant metastatic disease (i.e., a metastasis not in the same lymph node draining&#xD;
             area as the primary malignant melanoma). Histologic confirmation of stage IV is&#xD;
             required. Measurable disease that can be routinely assessed by physical examination&#xD;
             and/or non-invasive radiological procedures&#xD;
&#xD;
          -  Karnofsky performance status is at least 60% and life expectancy greater than 4 months&#xD;
&#xD;
          -  Male or female, minimum age 18 years&#xD;
&#xD;
          -  Written informed consent of the patient in accordance with good clinical practice and&#xD;
             local legislation&#xD;
&#xD;
          -  Availability of material for autologous Delayed Type Hypersensitivity (DTH) testing&#xD;
             (material derived from autologous melanoma metastases and in-house preparation&#xD;
             successful) is a requisite for entering the study&#xD;
&#xD;
          -  Patients have to undergo biopsy of at least one metastasis before the first and after&#xD;
             the last vaccination&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient who have received any chemotherapy, corticosteroids, radiotherapy&#xD;
             (stereotactic irradiation permitted), immunotherapy (e.g. Granulocyte Macrophage&#xD;
             Colony Stimulating Factor, Granulocyte Colony Stimulating Factor) or any other&#xD;
             investigational drugs in the 4 weeks prior to the first vaccination or prior to&#xD;
             surgical removal of tumor specimens for DTH material preparation (patients are not&#xD;
             permitted to receive such therapies 4 weeks prior to first cell inoculation except of&#xD;
             tumor reductive surgery which are medically indicated)&#xD;
&#xD;
          -  Patients with active intracranial metastases (CT/MRI) or choroidal melanoma&#xD;
&#xD;
          -  Patients with active autoimmune disease&#xD;
&#xD;
          -  Patients with organ allografts&#xD;
&#xD;
          -  Patients with evidence of one or more of the following infections: HIV-1, HIV-2,&#xD;
             Hepatitis B Virus, Hepatitis C Virus, Human T lymphotropic Virus-1&#xD;
&#xD;
          -  Patients with active systemic infections or other major medical illness of the&#xD;
             cardiovascular organ system [e.g. coronary heart disease (New York Heart Association&#xD;
             class III or IV), history of clinically significant ventricular arrhythmias or&#xD;
             angina], coagulation disorder, respiratory or nervous system disorder or with severe&#xD;
             endocrinological disease&#xD;
&#xD;
          -  Women of childbearing potential with a positive pregnancy test or without appropriate&#xD;
             contraception (e.g. IUD [ Intra-Uterine Device], oral contraceptives) until at least&#xD;
             28 days after the last vaccination&#xD;
&#xD;
          -  Lactating women&#xD;
&#xD;
          -  Impaired renal or hepatic function (serum creatinine &gt; 1.5 mg/dl or creatinine&#xD;
             clearance &lt; 75 ml/min). In amendments 1 and 3 serum creatinine levels were changed to&#xD;
             2.5 mg/dl and creatinine clearance was reduced to 30 ml/min&#xD;
&#xD;
          -  Impaired hematologic function with:&#xD;
&#xD;
               -  White Blood Count (WBC) &lt; 2500/mm**3 or&#xD;
&#xD;
               -  absolute lymphocyte count &lt; 1500/mm**3 or&#xD;
&#xD;
               -  hemoglobin &lt; 8 g/dl or&#xD;
&#xD;
               -  platelets &lt; 100,000/mm**3&#xD;
&#xD;
          -  Evidence for the existence or history of other malignant neoplasms (except adequately&#xD;
             treated basal cell carcinoma and carcinoma in situ of the cervix)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 29, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <last_update_submitted>July 30, 2014</last_update_submitted>
  <last_update_submitted_qc>July 30, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 31, 2014</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>
  <!-- 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/NCT02203864
org study id: 1155.2
nct id: NCT02203864
lead sponsor: 
Evaluation of safety and tolerability of four intradermal injections given at two week
      intervals. In addition the efficacy of transferrinfection was determined by quantifying
      Interleukin 2 (IL-2), which was locally produced by the implanted, transfected allogenic
      melanoma cells at the injection sites. Further determination of tumor specific and clinical
      host responses induced or augmented by the treatment were determined.
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of dose limiting toxicity (DLT)
time frame: up to 6 weeks
measure: Number of patients with adverse events
time frame: up to 28 days after the last vaccination
measure: Grading of local reactions on a 4-point-scale
time frame: up to 28 days after the last vaccination
measure: Number of patients with IL-2 transcripts in biopsies of injection sites
time frame: 4-6 and 48 hours after first vaccination
measure: Number of patients with delayed type hypersensitivity skin reaction
time frame: up to 28 days after the last vaccination
description: delayed type hypersensitivity testing
measure: Number of antigen-positive cells in biopsies from metastatic lesions
time frame: up to 28 days after the last vaccination
measure: Number of antigen-positive cells in the cellular infiltrate at the vaccination site
time frame: up to 28 days after the last vaccination
measure: Number of patients with a positive reaction to Multitest Merieux
time frame: up to day 14
description: positive reaction: sum of all indurations of all existing reactions => 10 mm (male) or >= 5 mm (female)
measure: Change in T cell proliferation as ratio of post-vaccination to pre-vaccination
time frame: up to 28 days after the last vaccination
measure: Change in S-100 beta protein level in serum
time frame: up to 28 days after the last vaccination
measure: Number of patients with clinical response
time frame: up to 28 days after the last vaccination
description: clinical response = complete and partial response
measure: Change in interferon-gamma secretion as ratio of post-vaccination to pre-vaccination
time frame: up to 28 days after the last vaccination
arm group label: BIBW2 with IL-2 secreting cell line
arm group type: Experimental
arm group label: BIBW2 without IL-2 secreting cell line
arm group type: Experimental
intervention type: Biological
intervention name: BIBW2 component A
description: BIBW2 without IL-2 secreting cell line
arm group label: BIBW2 without IL-2 secreting cell line
intervention type: Biological
intervention name: BIBW2 component B
description: BIBW2 with IL-2 secreting cell line
arm group label: BIBW2 with IL-2 secreting cell line
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Melanoma