<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/NCT01731587</url>
  </required_header>
  <id_info>
    <org_study_id>EMR 63325-019</org_study_id>
    <secondary_id>2012-001435-31</secondary_id>
    <nct_id>NCT01731587</nct_id>
  </id_info>
  <brief_title>Anti-cancer MUC1-specific Immunotherapy for Unresectable Stage III Non-small Cell Lung Cancer</brief_title>
  <acronym>FINGERPRINT</acronym>
  <official_title>Phase Ib, Single-arm, Proof-of-principle Trial Investigating the Cytokine Profile and Specific T Cell Response in Peripheral Blood of Non-small Cell Lung Cancer (NSCLC) Subjects With Unresected Stage III Disease Treated With L-BLP25</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck KGaA, Darmstadt, Germany</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase Ib study investigating whether liposome BLP25 mucin-1 (MUC1) peptide-specific&#xD;
      immunotherapy (L-BLP25) administered as weekly subcutaneous doses over 8 weeks following a&#xD;
      single dose of intravenous cyclophosphamide (CPA) induces a reproducible cytokine pattern&#xD;
      measured in the serum of unresected Stage III non-small cell lung cancer (NSCLC) subjects&#xD;
      after first-line chemo-radiation therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The objectives of this trial are no longer deemed appropriate for the clinical development of&#xD;
    L-BLP25 therefore this trial is withdrawn&#xD;
  </why_stopped>
  <start_date>January 2001</start_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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Immune response defined as change from baseline in serum cytokine levels after L-BLP25 administration at Week 1, 4 and 8</measure>
    <time_frame>Pre-dose (Day -3) up to 24 hours after L-BLP25 administration at Week 1, 4 and 8</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of a cellular immune response following treatment with L-BLP25</measure>
    <time_frame>Pre-dose (Day -3) and at 24 hours after L-BLP25 administration at Week 4 and 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in alternative immune or inflammatory serum soluble immune mediators such as interferon alpha (IFNα), transforming growth factor beta (TGFβ), or C-reactive protein (CRP) at 6, 12, and 24 hours after L-BLP25 administration.</measure>
    <time_frame>Pre-dose (Day -3) up to 24 hours after L-BLP25 administration at Week 1, 4 and 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events (AEs)</measure>
    <time_frame>Up to 6 weeks after the last dose of L-BLP25</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Non-small Cell Lung Cancer (NSCLC) Stage III</condition>
  <arm_group>
    <arm_group_label>L-BLP25 plus Cyclophosphamide (CPA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Biological: MUC1 peptide specific immunotherapy</intervention_name>
    <description>Eight consecutive weekly subcutaneous administration with reconstituted L-BLP25 (containing 806 microgram of BLP25 lipopeptide) followed by administrations at 6-week intervals, commencing at Week 14, until disease progression is documented.</description>
    <arm_group_label>L-BLP25 plus Cyclophosphamide (CPA)</arm_group_label>
    <other_name>EMD531444</other_name>
    <other_name>Stimuvax®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide (CPA)</intervention_name>
    <description>A single intravenous infusion of 300 milligram per square meter (to a maximum of 600 milligram) of CPA will be given three days before the first L-BLP25 administration.</description>
    <arm_group_label>L-BLP25 plus Cyclophosphamide (CPA)</arm_group_label>
    <other_name>L01AA01</other_name>
    <other_name>Endoxana</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically documented unresectable Stage III NSCLC, as defined by&#xD;
             American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC)&#xD;
             7th edition (2009) criteria. All histological subtypes are acceptable, including&#xD;
             bronchioalveolar carcinomas&#xD;
&#xD;
          -  Documented stable disease or objective response, according to Response Evaluation&#xD;
             Criteria In Solid Tumors (RECIST) Version 1.0, after primary chemo-radiotherapy&#xD;
             (either sequential or concomitant) for unresected Stage III disease, within 4 weeks&#xD;
             (28 days) prior to enrollment&#xD;
&#xD;
          -  Receipt of concomitant or sequential chemo-radiotherapy, consisting of a minimum of&#xD;
             two cycles of platinum-based chemotherapy and a minimum radiation dose of greater than&#xD;
             equal to 50 Gray. Subjects must have completed the primary thoracic chemo-radiotherapy&#xD;
             at least 4 weeks (28 days) and no later than 84 days prior to enrollment. Subjects who&#xD;
             received prophylactic brain irradiation as part of primary chemo-radiotherapy are&#xD;
             eligible&#xD;
&#xD;
          -  Platelet count greater than or equal to 140 * 10^9 per liter, white blood cell (WBC)&#xD;
             greater than or equal to 2.5 * 10^9 per liter, and hemoglobin greater than or equal to&#xD;
             90 gram per liter&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1&#xD;
&#xD;
        Additional Inclusion Criteria apply&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-therapies:&#xD;
&#xD;
               -  Previous lung cancer specific therapy (including surgery) other than primary&#xD;
                  chemo-radiotherapy&#xD;
&#xD;
               -  Receipt of immunotherapy within 4 weeks (28 days) prior to enrollment. Note:&#xD;
                  Subjects who have received monoclonal antibodies for imaging are acceptable&#xD;
&#xD;
               -  Receipt of investigational systemic drugs (including off-label use of approved&#xD;
                  products) within 4 weeks (28 days) prior to enrollment&#xD;
&#xD;
          -  Disease status:&#xD;
&#xD;
               -  Metastatic disease&#xD;
&#xD;
               -  Malignant pleural effusion at initial diagnosis and/or at trial entry&#xD;
&#xD;
               -  Past or current history of neoplasm other than lung carcinoma, except for&#xD;
                  curatively treated nonmelanoma skin cancer, in situ carcinoma of the cervix or&#xD;
                  other cancer curatively treated and with no evidence of disease for at least 5&#xD;
                  years&#xD;
&#xD;
               -  Autoimmune disease&#xD;
&#xD;
               -  A recognized immunodeficiency disease including cellular immunodeficiencies,&#xD;
                  hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary or&#xD;
                  congenital immunodeficiencies&#xD;
&#xD;
               -  Any preexisting medical condition requiring systemic chronic steroid or&#xD;
                  immunosuppressive therapy (steroids for the treatment of radiation pneumonitis&#xD;
                  are allowed)&#xD;
&#xD;
               -  Known Hepatitis B and/or C&#xD;
&#xD;
               -  Active infection at enrollment, including but not limited to, flu-like&#xD;
                  infections, urinary tract infections, bronchopulmonary infections, etc&#xD;
&#xD;
          -  Physiological functions:&#xD;
&#xD;
               -  Clinically significant hepatic dysfunction (that is, alanine aminotransferase&#xD;
                  [ALT] greater than 2.5 times normal upper limit [ULN]; or aspartate&#xD;
                  aminotransferase [AST] greater than 2.5 times ULN; or bilirubin greater than or&#xD;
                  equal to 1.5 * ULN)&#xD;
&#xD;
               -  Clinically significant renal dysfunction (that is, serum creatinine greater than&#xD;
                  or equal to 1.5 * ULN)&#xD;
&#xD;
               -  Clinically significant cardiac disease, for example, New York Heart Association&#xD;
                  (NYHA) Classes III-IV; uncontrolled angina, uncontrolled arrhythmia or&#xD;
                  uncontrolled hypertension, myocardial infarction in the previous 6 months as&#xD;
                  confirmed by an electrocardiogram (ECG)&#xD;
&#xD;
               -  Splenectomy&#xD;
&#xD;
               -  Infectious process that in the opinion of the investigator could compromise the&#xD;
                  subject's ability to mount an immune response&#xD;
&#xD;
        Additional Exclusion Criteria apply&#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>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck KGaA, Darmstadt, Germany</affiliation>
  </overall_official>
  <removed_countries>
    <country>Poland</country>
  </removed_countries>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>October 11, 2012</study_first_submitted>
  <study_first_submitted_qc>November 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2012</study_first_posted>
  <last_update_submitted>February 27, 2017</last_update_submitted>
  <last_update_submitted_qc>February 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non-small cell lung cancer (NSCLC)</keyword>
  <keyword>exploratory study</keyword>
  <keyword>L-BLP25</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
  </intervention_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/NCT01731587
org study id: EMR 63325-019
secondary id: 2012-001435-31
nct id: NCT01731587
lead sponsor: 
has dmc: No
Phase Ib study investigating whether liposome BLP25 mucin-1 (MUC1) peptide-specific
      immunotherapy (L-BLP25) administered as weekly subcutaneous doses over 8 weeks following a
      single dose of intravenous cyclophosphamide (CPA) induces a reproducible cytokine pattern
      measured in the serum of unresected Stage III non-small cell lung cancer (NSCLC) subjects
      after first-line chemo-radiation therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Immune response defined as change from baseline in serum cytokine levels after L-BLP25 administration at Week 1, 4 and 8
time frame: Pre-dose (Day -3) up to 24 hours after L-BLP25 administration at Week 1, 4 and 8
measure: Evaluation of a cellular immune response following treatment with L-BLP25
time frame: Pre-dose (Day -3) and at 24 hours after L-BLP25 administration at Week 4 and 8
measure: Change from baseline in alternative immune or inflammatory serum soluble immune mediators such as interferon alpha (IFNα), transforming growth factor beta (TGFβ), or C-reactive protein (CRP) at 6, 12, and 24 hours after L-BLP25 administration.
time frame: Pre-dose (Day -3) up to 24 hours after L-BLP25 administration at Week 1, 4 and 8
measure: Number of subjects with adverse events (AEs)
time frame: Up to 6 weeks after the last dose of L-BLP25
arm group label: L-BLP25 plus Cyclophosphamide (CPA)
arm group type: Experimental
intervention type: Other
intervention name: Biological: MUC1 peptide specific immunotherapy
description: Eight consecutive weekly subcutaneous administration with reconstituted L-BLP25 (containing 806 microgram of BLP25 lipopeptide) followed by administrations at 6-week intervals, commencing at Week 14, until disease progression is documented.
arm group label: L-BLP25 plus Cyclophosphamide (CPA)
other name: EMD531444
other name: Stimuvax®
intervention type: Drug
intervention name: Cyclophosphamide (CPA)
description: A single intravenous infusion of 300 milligram per square meter (to a maximum of 600 milligram) of CPA will be given three days before the first L-BLP25 administration.
arm group label: L-BLP25 plus Cyclophosphamide (CPA)
other name: L01AA01
other name: Endoxana
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Merck KGaA, Darmstadt, Germany
country: Poland
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Cyclophosphamide