<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/NCT01722149</url>
  </required_header>
  <id_info>
    <org_study_id>FAPME-1</org_study_id>
    <nct_id>NCT01722149</nct_id>
  </id_info>
  <brief_title>Re-directed T Cells for the Treatment (FAP)-Positive Malignant Pleural Mesothelioma</brief_title>
  <official_title>Phase I Study for the Adoptive Transfer of Re-directed FAP-specific T Cells in the Pleural Effusion of Patients With Malignant Pleural Mesothelioma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Zurich</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      MPM patients are not eligible for surgical procedures like decortication or&#xD;
      pleuro-pneumectomy and have a median survival of 12 months with palliative chemotherapy.&#xD;
      Therefore, new therapeutic approaches are of crucial need in this clinical situation. This is&#xD;
      a phase I trial for patients with malignant pleural mesothelioma with pleural effusion&#xD;
      testing the safety of a fixed single dose of 1x10e6 adoptively transferred FAP-specific&#xD;
      re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days&#xD;
      before transfer from peripheral blood. CD8 positive T cells will be isolated and&#xD;
      re-programmed by retroviral transfer of a chimeric antigen receptor (CAR) recognizing FAP&#xD;
      which serves as target structure in MPM.&#xD;
&#xD;
        -  Trial with immunomodulatory product / biological&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase I trial for patients with malignant pleural mesothelioma. A fixed single dose&#xD;
      of adoptively transferred FAP-specific CD8 positive re-directed T cells will be given in the&#xD;
      pleural effusion.&#xD;
&#xD;
      Three patients who are at the time point of screening not operable will be treated with&#xD;
      re-directed T cells administered into the pleural effusion after completion of 3 cycles of&#xD;
      palliative chemotherapy. In the case of one AE grade III/IV or one SAE - and the occurrence&#xD;
      of DLT both judged to be treatment related by an independent safety monitoring board - the&#xD;
      patient number will be expanded to 6 patients. The study will be stopped if one additional&#xD;
      DLT occurs also judged to be treatment related.&#xD;
&#xD;
      Patients will be treated with 1x10e6 re-directed FAP-specific T cells injected in the pleural&#xD;
      effusion. The study ends 35 days after adoptive T cell transfer. Re-directed FAP-specific T&#xD;
      cells will be administered at day 0 (day 14 of the third cycle of palliative chemotherapy).&#xD;
      The study is designed to demonstrate safety of 1x10e6 re-directed FAP-specific T cells. The&#xD;
      next patient will be enrolled earliest, when the previous patient completed day +14 and the&#xD;
      safety monitoring board has not declared any DLTs. The palliative chemotherapy is not part of&#xD;
      the study protocol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 19, 2015</start_date>
  <completion_date type="Actual">July 18, 2019</completion_date>
  <primary_completion_date type="Actual">March 22, 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Adoptive Transfer of re-directed FAP-specific T cells</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety</measure>
    <time_frame>until 35 days after transfer of re-directed T cells</time_frame>
    <description>Incidence and severity of treatment-related laboratory abnormalities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version v4.03 criteria as grade III-IV. In the case of one AE grade III/IV or one SAE the safety monitoring board will judge whether the case is treatment related and whether it have to be counted as DLT.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Malignant Pleural Mesothelioma</condition>
  <arm_group>
    <arm_group_label>Adoptive Transfer of re-directed T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Adoptive Transfer of re-directed FAP specific T cells in the pleural effusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Adoptive Transfer of re-directed T cells</intervention_name>
    <description>Adoptive Transfer of 10e6 re-directed T cells in the pleural effusion</description>
    <arm_group_label>Adoptive Transfer of re-directed T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed and documented malignant pleural&#xD;
             mesothelioma with pleural effusion,&#xD;
&#xD;
          -  Signed Informed Consent after being informed,&#xD;
&#xD;
          -  Patients medically and/or functionally at screening not accessible for surgical&#xD;
             treatment&#xD;
&#xD;
          -  Bone marrow function: hemoglobin &gt;/= 100 g/L; white blood cell count (WBC) &gt;/= 1.0 x&#xD;
             109/L; absolute neutrophile count (ANC) &gt;/= 0.5 x 109/L; platelet count &gt;/= 100 x&#xD;
             109/L,&#xD;
&#xD;
          -  Hepatic: aspartate transaminase (AST) and alanine transaminase (ALT) &lt;/= 2.5 times&#xD;
             upper limit of normal (ULN)); bilirubin &lt;/= 1.5 x ULN,&#xD;
&#xD;
          -  Renal: creatinine = 176 umol/l and creatinine clearance = 45 mL/min,&#xD;
&#xD;
          -  No concomitant treatment with systemic corticosteroids, or any other immunosuppressive&#xD;
             agents,&#xD;
&#xD;
          -  The patient has received no major organ allograft,&#xD;
&#xD;
          -  HIV-negative,&#xD;
&#xD;
          -  HBV and HCV negative,&#xD;
&#xD;
          -  No uncontrolled bleeding disorder,&#xD;
&#xD;
          -  Patients of child-producing potential must agree to use contraception while enrolled&#xD;
             in the study and for 24 months after the adoptive transfer.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Contra-indications to the class of TpP, e.g. known hypersensitivity or allergy to the&#xD;
             investigational product,&#xD;
&#xD;
          -  Contra-indications on ethical grounds,&#xD;
&#xD;
          -  Women who are pregnant or breast feeding,&#xD;
&#xD;
          -  Intention to become pregnant during the course of the study,&#xD;
&#xD;
          -  Lack of safe contraception: Safe contraception is defined as follows:Female and male&#xD;
             subjects of childbearing potential, using and willing to continue using a medically&#xD;
             reliable method of double barrier contraception for the entire study duration and the&#xD;
             next 2 years, such as oral, injectable, or implantable contraceptives, or intrauterine&#xD;
             contraceptive devices in combination with preservatives. Or subjects who are using any&#xD;
             other method considered sufficiently reliable by the investigator in individual&#xD;
             cases.Subjects who are surgically sterilized/hysterectomized or post-menopausal for&#xD;
             longer than 2 years are not considered as being of child bearing potential.&#xD;
&#xD;
          -  Known or suspected non-compliance, drug or alcohol abuse&#xD;
&#xD;
          -  Pericardial effusion of more than 100 ml. Pericardial involvement assessed by CT scan&#xD;
&#xD;
          -  Patients with medical history of coronary heart disease (CHD), stroke or peripheral&#xD;
             vascular disease (PVD),&#xD;
&#xD;
          -  Patients with medical history of autoimmune disease such as multiple sclerosis, lupus,&#xD;
             rheumatoid arthritis, inflammatory bowel disease or small vessel vasculitis,&#xD;
&#xD;
          -  Regular intake of immune-modulating drugs,&#xD;
&#xD;
          -  Inability to follow the procedures of the study, e.g. due to language problems,&#xD;
             psychological disorders, dementia or confusional state of the subject,&#xD;
&#xD;
          -  Participation in another study with investigational drug within the 30 days preceding&#xD;
             and during the present study,&#xD;
&#xD;
          -  Previous enrolment into the current study,&#xD;
&#xD;
          -  Enrolment of the investigator, his/her family members, employees and other dependent&#xD;
             persons.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alessandra Curioni, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Zurich, Division of Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Zurich, Division of Oncology</name>
      <address>
        <city>Zurich</city>
        <state>ZH</state>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Schuberth PC, Hagedorn C, Jensen SM, Gulati P, van den Broek M, Mischo A, Soltermann A, Jungel A, Marroquin Belaunzaran O, Stahel R, Renner C, Petrausch U. Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells. J Transl Med. 2013 Aug 12;11:187. doi: 10.1186/1479-5876-11-187.</citation>
    <PMID>23937772</PMID>
  </reference>
  <reference>
    <citation>Petrausch U, Schuberth PC, Hagedorn C, Soltermann A, Tomaszek S, Stahel R, Weder W, Renner C. Re-directed T cells for the treatment of fibroblast activation protein (FAP)-positive malignant pleural mesothelioma (FAPME-1). BMC Cancer. 2012 Dec 22;12:615. doi: 10.1186/1471-2407-12-615.</citation>
    <PMID>23259649</PMID>
  </reference>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>October 31, 2012</study_first_submitted>
  <study_first_submitted_qc>November 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <last_update_submitted>August 5, 2019</last_update_submitted>
  <last_update_submitted_qc>August 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>malignant pleural mesothelioma</keyword>
  <keyword>re-directed T cells</keyword>
  <keyword>FAP</keyword>
  <keyword>fibroblast activation protein</keyword>
  <keyword>CD8 positive T cells</keyword>
  <keyword>pleural effusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mesothelioma</mesh_term>
    <mesh_term>Mesothelioma, Malignant</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/NCT01722149
org study id: FAPME-1
nct id: NCT01722149
lead sponsor: 
has dmc: Yes
MPM patients are not eligible for surgical procedures like decortication or
      pleuro-pneumectomy and have a median survival of 12 months with palliative chemotherapy.
      Therefore, new therapeutic approaches are of crucial need in this clinical situation. This is
      a phase I trial for patients with malignant pleural mesothelioma with pleural effusion
      testing the safety of a fixed single dose of 1x10e6 adoptively transferred FAP-specific
      re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days
      before transfer from peripheral blood. CD8 positive T cells will be isolated and
      re-programmed by retroviral transfer of a chimeric antigen receptor (CAR) recognizing FAP
      which serves as target structure in MPM.

        -  Trial with immunomodulatory product / biological
This is a phase I trial for patients with malignant pleural mesothelioma. A fixed single dose
      of adoptively transferred FAP-specific CD8 positive re-directed T cells will be given in the
      pleural effusion.

      Three patients who are at the time point of screening not operable will be treated with
      re-directed T cells administered into the pleural effusion after completion of 3 cycles of
      palliative chemotherapy. In the case of one AE grade III/IV or one SAE - and the occurrence
      of DLT both judged to be treatment related by an independent safety monitoring board - the
      patient number will be expanded to 6 patients. The study will be stopped if one additional
      DLT occurs also judged to be treatment related.

      Patients will be treated with 1x10e6 re-directed FAP-specific T cells injected in the pleural
      effusion. The study ends 35 days after adoptive T cell transfer. Re-directed FAP-specific T
      cells will be administered at day 0 (day 14 of the third cycle of palliative chemotherapy).
      The study is designed to demonstrate safety of 1x10e6 re-directed FAP-specific T cells. The
      next patient will be enrolled earliest, when the previous patient completed day +14 and the
      safety monitoring board has not declared any DLTs. The palliative chemotherapy is not part of
      the study protocol.
intervention model: Sequential Assignment
intervention model description: Adoptive Transfer of re-directed FAP-specific T cells
primary purpose: Treatment
masking: None (Open Label)
measure: Safety
time frame: until 35 days after transfer of re-directed T cells
description: Incidence and severity of treatment-related laboratory abnormalities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version v4.03 criteria as grade III-IV. In the case of one AE grade III/IV or one SAE the safety monitoring board will judge whether the case is treatment related and whether it have to be counted as DLT.
arm group label: Adoptive Transfer of re-directed T cells
arm group type: Experimental
description: Adoptive Transfer of re-directed FAP specific T cells in the pleural effusion
intervention type: Genetic
intervention name: Adoptive Transfer of re-directed T cells
description: Adoptive Transfer of 10e6 re-directed T cells in the pleural effusion
arm group label: Adoptive Transfer of re-directed T cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Alessandra Curioni, MD
role: Principal Investigator
affiliation: University Hospital Zurich, Division of Oncology
facility: 
country: Switzerland
citation: Schuberth PC, Hagedorn C, Jensen SM, Gulati P, van den Broek M, Mischo A, Soltermann A, Jungel A, Marroquin Belaunzaran O, Stahel R, Renner C, Petrausch U. Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells. J Transl Med. 2013 Aug 12;11:187. doi: 10.1186/1479-5876-11-187.
PMID: 23937772
citation: Petrausch U, Schuberth PC, Hagedorn C, Soltermann A, Tomaszek S, Stahel R, Weder W, Renner C. Re-directed T cells for the treatment of fibroblast activation protein (FAP)-positive malignant pleural mesothelioma (FAPME-1). BMC Cancer. 2012 Dec 22;12:615. doi: 10.1186/1471-2407-12-615.
PMID: 23259649
responsible party type: Sponsor
mesh term: Mesothelioma
mesh term: Mesothelioma, Malignant