<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/NCT01663571</url>
  </required_header>
  <id_info>
    <org_study_id>11-01293</org_study_id>
    <nct_id>NCT01663571</nct_id>
  </id_info>
  <brief_title>STAT3 in T Cells: At The Crossroads of Inflammation and Cancer</brief_title>
  <official_title>STAT3 in T Cells: At The Crossroads of Inflammation and Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NYU Langone Health</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>
      Protocol Summary&#xD;
&#xD;
      Constitutive STAT3 activity is implicated in many malignancies including Cutaneous T Cell&#xD;
      Lymphoma. It is also essential for Th17 differentiation, a subset of CD4 effector T cell,&#xD;
      implicated in chronic inflammatory conditions and possibly CTCL. HDAC inhibitors have shown&#xD;
      activity in CTCL but their exact mechanism of action is not known. It is known that HDAC&#xD;
      inhibitors regulate STAT3 transcriptional activity and hence can potentially be active in&#xD;
      CTCL through modulation of the STAT3 pathway. The hypothesis is that Th17 cytokines&#xD;
      contribute to the initiation of cancer by creating a pro-inflammatory microenvironment that&#xD;
      predisposes cells to neoplastic transformation. To probe this, the investigators will compare&#xD;
      the differences in cytokine production and gene expression in the skin resident T cells from&#xD;
      patients with benign dermatoses and CTCL as well as in the blood/circulating lymphocytes of&#xD;
      healthy donors and Sezary syndrome (SS). The investigators will also investigate whether HDAC&#xD;
      inhibitors have a direct impact on the number of Th17 cells, the cytokine production by these&#xD;
      cells and phosphorylated STAT3 protein in CTCL with subsequent treatment cycles.&#xD;
&#xD;
      The objectives of this study are 1. Observe the epigenetic, transcriptional and phenotypic&#xD;
      changes that take place in T cell during malignant transformation 2. Understand the mechanism&#xD;
      of action of HDAC inhibitors in CTCL.&#xD;
&#xD;
      Methods: Skin biopsy specimens from cutaneous T cell lymphoma (CTCL) patients and benign skin&#xD;
      conditions namely eczema, dermatitis and psoriasis will be obtained through a standard punch&#xD;
      biopsy procedure from the skin lesion.&#xD;
&#xD;
      Additionally, 15 ml of peripheral blood from CTCL patients who have Sezary syndrome (SS) and&#xD;
      from patients with benign skin condition will be collected.&#xD;
&#xD;
      CTCL patients, who are starting treatment with HDAC Inhibitors namely Vorinostat and&#xD;
      Romidepsin, will have a total of 3 skin biopsies and/or blood draws. The first procedure&#xD;
      would be before starting treatment with either of these HDAC inhibitors. Two more skin&#xD;
      biopsies and/or blood draws will be performed after first and second cycle of treatment.&#xD;
&#xD;
      Levels of Th17 cytokines, IL-17, IL -22 and pSTAT3 protein will be determined by IHC staining&#xD;
      in the skin and cytokine levels in the blood will be assayed by sandwich ELISA method.The&#xD;
      investigators will also assay the mRNA levels of the transcription factors of the different T&#xD;
      effector cells by qPCR.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study is permanently closed to enrollment .Collection of private identifiable information is&#xD;
    complete Analysis of private identifiable information is complete&#xD;
  </why_stopped>
  <start_date type="Actual">May 1, 2012</start_date>
  <completion_date type="Actual">November 21, 2016</completion_date>
  <primary_completion_date type="Actual">November 21, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Measure the levels of Th 17 cytokines namely Il-17 and Il-22 in CTCL</measure>
    <time_frame>2 -3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identify STAT3 mutations in CTCL</measure>
    <time_frame>2-3 years</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">35</enrollment>
  <condition>Cutaneous T Cell Lymphoma</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Skin biopsy specimens from cutaneous T cell lymphoma (CTCL) patients and benign skin&#xD;
      conditions namely eczema, dermatitis and psoriasis will be obtained through a standard punch&#xD;
      biopsy procedure from the skin lesion. The investigators will assay the mRNA levels of the&#xD;
      transcription factors of the different T effector cells by qPCR.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with Cutaneous T cell Lymphoma (CTCL), either newly diagnosed or with progression&#xD;
        of disease. Patients with Eczema, psoriasis and dermatitis are also eligible for the study&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients with CTCL that are starting new form of treatment and adult patients&#xD;
             with benign dermatoses.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients with lymphomas other than CTCL or leukemia&#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>Sergei Koralov, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NYU Langone Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>August 9, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <last_update_submitted>September 13, 2018</last_update_submitted>
  <last_update_submitted_qc>September 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 2018</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>Lymphoma, T-Cell, Cutaneous</mesh_term>
    <mesh_term>Inflammation</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/NCT01663571
org study id: 11-01293
nct id: NCT01663571
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Protocol Summary

      Constitutive STAT3 activity is implicated in many malignancies including Cutaneous T Cell
      Lymphoma. It is also essential for Th17 differentiation, a subset of CD4 effector T cell,
      implicated in chronic inflammatory conditions and possibly CTCL. HDAC inhibitors have shown
      activity in CTCL but their exact mechanism of action is not known. It is known that HDAC
      inhibitors regulate STAT3 transcriptional activity and hence can potentially be active in
      CTCL through modulation of the STAT3 pathway. The hypothesis is that Th17 cytokines
      contribute to the initiation of cancer by creating a pro-inflammatory microenvironment that
      predisposes cells to neoplastic transformation. To probe this, the investigators will compare
      the differences in cytokine production and gene expression in the skin resident T cells from
      patients with benign dermatoses and CTCL as well as in the blood/circulating lymphocytes of
      healthy donors and Sezary syndrome (SS). The investigators will also investigate whether HDAC
      inhibitors have a direct impact on the number of Th17 cells, the cytokine production by these
      cells and phosphorylated STAT3 protein in CTCL with subsequent treatment cycles.

      The objectives of this study are 1. Observe the epigenetic, transcriptional and phenotypic
      changes that take place in T cell during malignant transformation 2. Understand the mechanism
      of action of HDAC inhibitors in CTCL.

      Methods: Skin biopsy specimens from cutaneous T cell lymphoma (CTCL) patients and benign skin
      conditions namely eczema, dermatitis and psoriasis will be obtained through a standard punch
      biopsy procedure from the skin lesion.

      Additionally, 15 ml of peripheral blood from CTCL patients who have Sezary syndrome (SS) and
      from patients with benign skin condition will be collected.

      CTCL patients, who are starting treatment with HDAC Inhibitors namely Vorinostat and
      Romidepsin, will have a total of 3 skin biopsies and/or blood draws. The first procedure
      would be before starting treatment with either of these HDAC inhibitors. Two more skin
      biopsies and/or blood draws will be performed after first and second cycle of treatment.

      Levels of Th17 cytokines, IL-17, IL -22 and pSTAT3 protein will be determined by IHC staining
      in the skin and cytokine levels in the blood will be assayed by sandwich ELISA method.The
      investigators will also assay the mRNA levels of the transcription factors of the different T
      effector cells by qPCR.
observational model: Case-Only
time perspective: Prospective
measure: Measure the levels of Th 17 cytokines namely Il-17 and Il-22 in CTCL
time frame: 2 -3 years
measure: Identify STAT3 mutations in CTCL
time frame: 2-3 years
Skin biopsy specimens from cutaneous T cell lymphoma (CTCL) patients and benign skin
      conditions namely eczema, dermatitis and psoriasis will be obtained through a standard punch
      biopsy procedure from the skin lesion. The investigators will assay the mRNA levels of the
      transcription factors of the different T effector cells by qPCR.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sergei Koralov, PhD
role: Principal Investigator
affiliation: NYU School of Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma, T-Cell, Cutaneous
mesh term: Inflammation