<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/NCT01686594</url>
  </required_header>
  <id_info>
    <org_study_id>EudraCT 2012-000212-28</org_study_id>
    <secondary_id>24-169 ex 11/12</secondary_id>
    <nct_id>NCT01686594</nct_id>
  </id_info>
  <brief_title>PUVA Maintenance Therapy in Mycosis Fungoides</brief_title>
  <acronym>M_PUVA_2012</acronym>
  <official_title>A Multi-center, Randomized Study on Oral 8-methoxypsoralen Plus UVA With or Without Maintenance Therapy in Mycosis Fungoides EORTC/ISCL Stage IA to IIB</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Graz</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine whether psoralen plus UVA (PUVA) photochemotherapy&#xD;
      maintenance treatment prolongs disease-free survival of cutaneous T cell lymphoma (mycosis&#xD;
      fungoides) patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Psoralen plus UVA (PUVA) photochemotherapy consists of the topical or oral&#xD;
      application of psoralen, followed by exposure to UVA light. PUVA is used in various&#xD;
      conditions, including early stages of mycosis fungoides (MF) and other primary and secondary&#xD;
      lymphoproliferative disorders. PUVA has strong pro-apoptotic and immunomodulating properties,&#xD;
      but the exact mechanisms by which PUVA leads to clearance of MF are not well understood.&#xD;
      Although MF is generally a slowly progressing disease, it ultimately can spread to lymphoid&#xD;
      tissues, peripheral blood, and other organs, leading to death.&#xD;
&#xD;
      Previous Work: PUVA therapy is a well-accepted first-line treatment option for skin-limited&#xD;
      MF (stages IA, IB, and IIA), leading to complete remission in a high portion of patients&#xD;
      (approximately 70 to 90%). Long-term remissions can be achieved with PUVA in a certain&#xD;
      percentage of patients. However, in most cases MF lesions relapse after stop of PUVA after&#xD;
      variable time intervals with a median time to relapse of 14 to 17 month, according to our own&#xD;
      experience. Not only is little is known about the therapeutic mechanisms of PUVA in MF but as&#xD;
      little is known about optimal duration and frequency of treatment (2, 3, or 4 times weekly),&#xD;
      dose escalation, and maintenance therapy. Although PUVA has been introduced more than 30&#xD;
      years ago, there is lack of prospective controlled studies with clearly defined dose schemes&#xD;
      and also an ongoing controversy whether PUVA maintenance therapy may prolong disease&#xD;
      remission in MF upon initial complete clearance.&#xD;
&#xD;
      Hypothesis &amp; Intended Work: We hypothesize that PUVA prolongs disease free survival in MF&#xD;
      patients. In a randomized multicenter trial involving 9 centers in Austria, we plan to&#xD;
      investigate (1) the clinical efficacy of PUVA and its maintenance therapy in MF and, (2) the&#xD;
      mechanisms by which PUVA leads to disease clearance. In total, 82 patients will be enrolled&#xD;
      and treated with a defined PUVA regimen with 2 exposures per week for 12 to 24 weeks. After&#xD;
      12 to 24 weeks of PUVA treatment, patients with complete remission will be randomized into&#xD;
      two arms. In Arm A patients will be treated with PUVA maintenance therapy at constant single&#xD;
      UVA doses. Maintenance treatment will be given once a week for one month (4 weeks), every 2&#xD;
      weeks for 2 months (8 weeks) and after three months once a month over 6 months. After 9&#xD;
      months of maintenance therapy patients will discontinue therapy. Patients in Arm B will&#xD;
      receive no therapy. All patients will be followed until recurrence or at least 12 months (in&#xD;
      non-recurrent patients) when the primary study analysis will be done. In addition, the&#xD;
      follow-up will be extended to 60 months for long-term results.&#xD;
&#xD;
      The mechanistic action of PUVA will be studied by laboratory investigations, including immune&#xD;
      function and cytokine analysis.&#xD;
&#xD;
      Outlook: A better understanding of the optimal regimen and the therapeutic mechanisms of PUVA&#xD;
      in MF should help improving treatment strategies for this life-threatening disease. The&#xD;
      understanding of the mode of action of PUVA in MF may also help to develop novel treatments&#xD;
      using PUVA-affected pathways, allowing to achieve overall better long-term response and&#xD;
      success.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">July 2, 2018</completion_date>
  <primary_completion_date type="Actual">July 2, 2018</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recurrence after complete remission within 12 months post therapy</measure>
    <time_frame>12 months after end of therapy</time_frame>
    <description>Recurrence is defined as mSWAT (modified severity weighted assessment tool ) &gt;0.&#xD;
The primary outcome will be evaluated by survival analysis (log-rank test; Kaplan-Meier) comparing time to recurrence after complete remission between patients treated with maintenance therapy vs. patients without maintenance therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72</time_frame>
    <description>Compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HADS</measure>
    <time_frame>Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72</time_frame>
    <description>Hospital anxiety depression score, compared to baseline;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine response in serum</measure>
    <time_frame>Week -4 to 0; week 6, 12, 24, and 48</time_frame>
    <description>Compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of regulatory T cells</measure>
    <time_frame>Week -4 to 0; week 6, 12, 24, and 48</time_frame>
    <description>Compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Function of regulatory T cells</measure>
    <time_frame>Week -4 to 0; week 6, 12, 24, and 48</time_frame>
    <description>Compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microscopic alterations</measure>
    <time_frame>Week -4 to 0; and week 6; optional at week 12, 24, and 48; and in the follow-up from year 1 to 5</time_frame>
    <description>Quantification of histologic response in skin biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine expression in the skin</measure>
    <time_frame>Week -4 to 0; and week 6; optional at week 12, 24, and 48; and in the follow-up from year 1 to 5</time_frame>
    <description>Rt-PCR and immunohistochemical staining investigations</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Patch/Plaque Stage Mycosis Fungoides</condition>
  <arm_group>
    <arm_group_label>PUVA maintenance treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Psoralen plus UVA (PUVA) treatment. The patients receive a standardized dose of oral 8-methoxypsoralen (Oxsoralen) 1 hour before UVA exposure</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No maintenance treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>observation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>8-methoxypsoralen</intervention_name>
    <description>8-methoxypsoralen 10mg per 20 kg body weight 1 hour before UVA exposure</description>
    <arm_group_label>PUVA maintenance treatment</arm_group_label>
    <other_name>Oxsoralen®; Gerot Pharmazeutika GmbH, Vienna, Austria</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histopathologically documented MF clinical stage IA-IIB (see Table1) confirmed by&#xD;
             current or previous diagnostic lesion biopsy&#xD;
&#xD;
          -  A Karnofsky performance score &gt; 60&#xD;
&#xD;
          -  No previous PUVA treatment&#xD;
&#xD;
          -  Anti-ds-DNA (antinuclear antibodies) or anti-Ro/La antibodies: negative&#xD;
&#xD;
          -  Acceptable organ function defined as follows:&#xD;
&#xD;
        SGOT (AST) and SGPT (ALT) &lt; 2.5 times the upper limit of normal for the institution&#xD;
&#xD;
          -  Creatinine &lt; 2 times the upper limit of normal for the institution&#xD;
&#xD;
          -  No evidence of severe cardiac insufficiency (NYHA grade III-IV)&#xD;
&#xD;
          -  Women of child bearing potential must have a negative serum pregnancy test (ß-HCG)&#xD;
             within seven (7) days prior to randomization&#xD;
&#xD;
          -  Absence of any serious intercurrent illness or infection at time of entry into the&#xD;
             study that could interfere with planned treatment&#xD;
&#xD;
          -  Patients must be willing to accept limiting sun exposure on the day receiving PUVA&#xD;
             treatment&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy and Lactation&#xD;
&#xD;
          -  Photosensitive diseases such as lupus erythematosus or basal cell nevus syndrome&#xD;
&#xD;
          -  Skin cancer syndromes such as xeroderma pigmentosum or basal cell nevus syndrome&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>82 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Wolf, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Graz</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of Graz</name>
      <address>
        <city>Graz</city>
        <zip>8010</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Dermatology, Medical University of Innsbruck</name>
      <address>
        <city>Innsbruck</city>
        <zip>A-6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Dermatology, General Hospital of the City of Linz</name>
      <address>
        <city>Linz</city>
        <zip>A-4021</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Dermatology, Hospital Salzburg - Paracelsus Private Medical University</name>
      <address>
        <city>Salzburg</city>
        <zip>A-5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Dermatology, County Hospital St. Pölten</name>
      <address>
        <city>St. Pölten</city>
        <zip>A-3100</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Dermatology, Medical University of Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>A-1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Dermatology, Hospital Hietzing</name>
      <address>
        <city>Vienna</city>
        <zip>A-1130</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Dermatology, Klinikum Wels</name>
      <address>
        <city>Wels</city>
        <zip>A-4600</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Dermatology, County Hospital Wiener Neustadt</name>
      <address>
        <city>Wiener Neustadt</city>
        <zip>A-2700</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>May 9, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <last_update_submitted>November 12, 2018</last_update_submitted>
  <last_update_submitted_qc>November 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Graz</investigator_affiliation>
    <investigator_full_name>Peter Wolf, MD</investigator_full_name>
    <investigator_title>Univ.Prof. Dr.</investigator_title>
  </responsible_party>
  <keyword>Mycosis fungoides</keyword>
  <keyword>Psoralen and UVA (PUVA)</keyword>
  <keyword>Photochemotherapy</keyword>
  <keyword>Maintenance treatment</keyword>
  <keyword>Immune function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycoses</mesh_term>
    <mesh_term>Mycosis Fungoides</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methoxsalen</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 23, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/94/NCT01686594/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT01686594
org study id: EudraCT 2012-000212-28
secondary id: 24-169 ex 11/12
nct id: NCT01686594
lead sponsor: 
has dmc: No
The purpose of the study is to determine whether psoralen plus UVA (PUVA) photochemotherapy
      maintenance treatment prolongs disease-free survival of cutaneous T cell lymphoma (mycosis
      fungoides) patients.
Background: Psoralen plus UVA (PUVA) photochemotherapy consists of the topical or oral
      application of psoralen, followed by exposure to UVA light. PUVA is used in various
      conditions, including early stages of mycosis fungoides (MF) and other primary and secondary
      lymphoproliferative disorders. PUVA has strong pro-apoptotic and immunomodulating properties,
      but the exact mechanisms by which PUVA leads to clearance of MF are not well understood.
      Although MF is generally a slowly progressing disease, it ultimately can spread to lymphoid
      tissues, peripheral blood, and other organs, leading to death.

      Previous Work: PUVA therapy is a well-accepted first-line treatment option for skin-limited
      MF (stages IA, IB, and IIA), leading to complete remission in a high portion of patients
      (approximately 70 to 90%). Long-term remissions can be achieved with PUVA in a certain
      percentage of patients. However, in most cases MF lesions relapse after stop of PUVA after
      variable time intervals with a median time to relapse of 14 to 17 month, according to our own
      experience. Not only is little is known about the therapeutic mechanisms of PUVA in MF but as
      little is known about optimal duration and frequency of treatment (2, 3, or 4 times weekly),
      dose escalation, and maintenance therapy. Although PUVA has been introduced more than 30
      years ago, there is lack of prospective controlled studies with clearly defined dose schemes
      and also an ongoing controversy whether PUVA maintenance therapy may prolong disease
      remission in MF upon initial complete clearance.

      Hypothesis & Intended Work: We hypothesize that PUVA prolongs disease free survival in MF
      patients. In a randomized multicenter trial involving 9 centers in Austria, we plan to
      investigate (1) the clinical efficacy of PUVA and its maintenance therapy in MF and, (2) the
      mechanisms by which PUVA leads to disease clearance. In total, 82 patients will be enrolled
      and treated with a defined PUVA regimen with 2 exposures per week for 12 to 24 weeks. After
      12 to 24 weeks of PUVA treatment, patients with complete remission will be randomized into
      two arms. In Arm A patients will be treated with PUVA maintenance therapy at constant single
      UVA doses. Maintenance treatment will be given once a week for one month (4 weeks), every 2
      weeks for 2 months (8 weeks) and after three months once a month over 6 months. After 9
      months of maintenance therapy patients will discontinue therapy. Patients in Arm B will
      receive no therapy. All patients will be followed until recurrence or at least 12 months (in
      non-recurrent patients) when the primary study analysis will be done. In addition, the
      follow-up will be extended to 60 months for long-term results.

      The mechanistic action of PUVA will be studied by laboratory investigations, including immune
      function and cytokine analysis.

      Outlook: A better understanding of the optimal regimen and the therapeutic mechanisms of PUVA
      in MF should help improving treatment strategies for this life-threatening disease. The
      understanding of the mode of action of PUVA in MF may also help to develop novel treatments
      using PUVA-affected pathways, allowing to achieve overall better long-term response and
      success.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recurrence after complete remission within 12 months post therapy
time frame: 12 months after end of therapy
description: Recurrence is defined as mSWAT (modified severity weighted assessment tool ) >0.
The primary outcome will be evaluated by survival analysis (log-rank test; Kaplan-Meier) comparing time to recurrence after complete remission between patients treated with maintenance therapy vs. patients without maintenance therapy.
measure: Quality of life
time frame: Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72
description: Compared to baseline
measure: HADS
time frame: Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72
description: Hospital anxiety depression score, compared to baseline;
measure: Cytokine response in serum
time frame: Week -4 to 0; week 6, 12, 24, and 48
description: Compared to baseline
measure: Levels of regulatory T cells
time frame: Week -4 to 0; week 6, 12, 24, and 48
description: Compared to baseline
measure: Function of regulatory T cells
time frame: Week -4 to 0; week 6, 12, 24, and 48
description: Compared to baseline
measure: Microscopic alterations
time frame: Week -4 to 0; and week 6; optional at week 12, 24, and 48; and in the follow-up from year 1 to 5
description: Quantification of histologic response in skin biopsy
measure: Cytokine expression in the skin
time frame: Week -4 to 0; and week 6; optional at week 12, 24, and 48; and in the follow-up from year 1 to 5
description: Rt-PCR and immunohistochemical staining investigations
arm group label: PUVA maintenance treatment
arm group type: Active Comparator
description: Psoralen plus UVA (PUVA) treatment. The patients receive a standardized dose of oral 8-methoxypsoralen (Oxsoralen) 1 hour before UVA exposure
arm group label: No maintenance treatment
arm group type: No Intervention
description: observation
intervention type: Drug
intervention name: 8-methoxypsoralen
description: 8-methoxypsoralen 10mg per 20 kg body weight 1 hour before UVA exposure
arm group label: PUVA maintenance treatment
other name: Oxsoralen®; Gerot Pharmazeutika GmbH, Vienna, Austria
criteria: 
gender: All
minimum age: 18 Years
maximum age: 82 Years
healthy volunteers: No
last name: Peter Wolf, MD
role: Principal Investigator
affiliation: Medical University of Graz
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University of Graz
investigator full name: Peter Wolf, MD
investigator title: Univ.Prof. Dr.
mesh term: Mycoses
mesh term: Mycosis Fungoides
mesh term: Methoxsalen
provided document: 