<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/NCT02251964</url>
  </required_header>
  <id_info>
    <org_study_id>NL49534.100.14</org_study_id>
    <secondary_id>2013-005269-37</secondary_id>
    <nct_id>NCT02251964</nct_id>
  </id_info>
  <brief_title>Rituximab in Interstitial Pneumonitis</brief_title>
  <acronym>RITUX-IP</acronym>
  <official_title>Rituximab in Life Threatening Therapy Resistant Progressive Interstitial Pneumonitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Human Adams</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amsterdam UMC, location VUmc</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Antonius Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This project will address rare immune mediated inflammatory diseases (IMIDs) involving the&#xD;
      lungs, i.e. interstitial pneumonitis (IP). The main objective of this study is to assess the&#xD;
      effects of rituximab (RTX) as a rescue therapy for progressive IMID-IP patients. The primary&#xD;
      study parameter is pulmonary function.&#xD;
&#xD;
      The secondary objectives are to explore the application of imaging with radiolabeled RTX as&#xD;
      early predictor for efficacy of RTX, to study the effects of RTX treatment on quality of&#xD;
      life, and to further elucidate the pathophysiology of IMID-IP by analyzing biochemical&#xD;
      markers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">February 2018</completion_date>
  <primary_completion_date type="Actual">October 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pulmonary function (VC, DLCO)</measure>
    <time_frame>6 - 12 months</time_frame>
    <description>establish a change from the downward decline in pulmonary function (absolute values and values predicted of VC = Vital Capacity and DLCO = Diffusion capacity of Lung Carbon monoxide)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Zr-89 Immuno PET</measure>
    <time_frame>3, 6 days after injection</time_frame>
    <description>This is a scan with radiolabelled rituximab (visualizing rituximab activity in the lungs). Calculated activity (SUV) in the lungs vs. blood pool vs liver vs.control group (n=15) is measured with standard deviation. The amount of uptake in the lungs and the clinical response of patients will be correlated to determine a correlation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Lung Diseases, Interstitial</condition>
  <condition>Pneumonitis, Interstitial</condition>
  <arm_group>
    <arm_group_label>rituximab</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>single arm study with Zr-89-rituximab immuno PET/CT</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>2 times 1000mg dose at 14 days interval treatment</description>
    <arm_group_label>rituximab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Zr-89-rituximab immuno PET/CT</intervention_name>
    <description>Immuno labeled PET/CT of the lungs</description>
    <arm_group_label>rituximab</arm_group_label>
    <other_name>Immuno PET</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        In order to be eligible to participate in the study, subjects must meet all of the&#xD;
        following criteria:&#xD;
&#xD;
          -  Age 18 to 70 years&#xD;
&#xD;
          -  No previous therapy with rituximab&#xD;
&#xD;
          -  At least 2 pulmonary function tests within past 6 months&#xD;
&#xD;
          -  Diagnosis of co-existing IMID and a severe and / or progressive IP characterized by 3&#xD;
             out of the following items:&#xD;
&#xD;
          -  Respiratory symptoms consistent with interstitial lung disease&#xD;
&#xD;
          -  Diagnosis of usual interstitial pneumonia (UIP), non-specific interstitial pneumonia&#xD;
             (NSIP), organizing pneumonia (OP) or a mixed form of UIP / NSIP / OP by either of the&#xD;
             following:&#xD;
&#xD;
          -  Open or video-assisted thoracic surgery (VATS) lung biopsy showing definite or&#xD;
             probable UIP / NSIP / OP&#xD;
&#xD;
          -  High Resolution Computer Tomography (HRCT) scan showing definite or probable&#xD;
             UIP/NSIP/OP/mixed&#xD;
&#xD;
          -  Forced Vital Capacity (FVC) &lt; 50% predicted and/or diffusing capacity of the lung for&#xD;
             carbon monoxide (DLCO) &lt; 40% predicted or worsening of lung function as demonstrated&#xD;
             by any one of the following within the past year:&#xD;
&#xD;
          -  &gt; 10% decrease in FVC&#xD;
&#xD;
          -  &gt; 15% decrease in DLCO&#xD;
&#xD;
          -  Therapy resistance to 1st (corticosteroids) and 2nd line therapy(cyclophosphamide or&#xD;
             azathioprine)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A potential subject who meets any of the following criteria will be excluded from&#xD;
        participation in this study:&#xD;
&#xD;
          -  Residual volume &gt;120% predicted at screening&#xD;
&#xD;
          -  DLCO &lt;25% of predicted value at screening + resting Oxygen Saturation (SAO2) without&#xD;
             external oxygen &lt;90%&#xD;
&#xD;
          -  History of unstable or deteriorating cardiac or neurological disease&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Hematology lower than specified limits (leucocytes)&#xD;
&#xD;
          -  Positive HIV, hepatitis B or C serology&#xD;
&#xD;
          -  Pre-existing conditions which lead to a life expectancy of less than 6 months&#xD;
&#xD;
          -  Receipt of any vaccine, particularly live viral vaccines, within 4 weeks before first&#xD;
             rituximab dose&#xD;
&#xD;
          -  Hypersensitivity for murine proteins&#xD;
&#xD;
        NOTE:&#xD;
&#xD;
          -  Fever (&gt;37,9 °C) at presentation is reason to delay therapy by 1 week&#xD;
&#xD;
          -  Evidence of active infection is reason to postpone rituximab treatment until no&#xD;
             further signs of active infection&#xD;
&#xD;
          -  Severe renal impairment is not a contraindication for rituximab therapy, however, if&#xD;
             patients (might) require dialysis frequently they will be excluded from the study&#xD;
             group&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>J C Grutters, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Antonius Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Antonius Hospital</name>
      <address>
        <city>Nieuwegein</city>
        <state>Utrecht</state>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <last_update_submitted>May 30, 2018</last_update_submitted>
  <last_update_submitted_qc>May 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 31, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>St. Antonius Hospital</investigator_affiliation>
    <investigator_full_name>Human Adams</investigator_full_name>
    <investigator_title>Prof. Dr. D.H. Biesma</investigator_title>
  </responsible_party>
  <keyword>IMID</keyword>
  <keyword>Interstitial Pneumonitis</keyword>
  <keyword>rituximab</keyword>
  <keyword>Immuno PET</keyword>
  <keyword>PET/CT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Interstitial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</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/NCT02251964
org study id: NL49534.100.14
secondary id: 2013-005269-37
nct id: NCT02251964
lead sponsor: 
collaborator: 
has dmc: No
This project will address rare immune mediated inflammatory diseases (IMIDs) involving the
      lungs, i.e. interstitial pneumonitis (IP). The main objective of this study is to assess the
      effects of rituximab (RTX) as a rescue therapy for progressive IMID-IP patients. The primary
      study parameter is pulmonary function.

      The secondary objectives are to explore the application of imaging with radiolabeled RTX as
      early predictor for efficacy of RTX, to study the effects of RTX treatment on quality of
      life, and to further elucidate the pathophysiology of IMID-IP by analyzing biochemical
      markers.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pulmonary function (VC, DLCO)
time frame: 6 - 12 months
description: establish a change from the downward decline in pulmonary function (absolute values and values predicted of VC = Vital Capacity and DLCO = Diffusion capacity of Lung Carbon monoxide)
measure: Zr-89 Immuno PET
time frame: 3, 6 days after injection
description: This is a scan with radiolabelled rituximab (visualizing rituximab activity in the lungs). Calculated activity (SUV) in the lungs vs. blood pool vs liver vs.control group (n=15) is measured with standard deviation. The amount of uptake in the lungs and the clinical response of patients will be correlated to determine a correlation.
arm group label: rituximab
arm group type: Other
description: single arm study with Zr-89-rituximab immuno PET/CT
intervention type: Drug
intervention name: Rituximab
description: 2 times 1000mg dose at 14 days interval treatment
arm group label: rituximab
intervention type: Radiation
intervention name: Zr-89-rituximab immuno PET/CT
description: Immuno labeled PET/CT of the lungs
arm group label: rituximab
other name: Immuno PET
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: J C Grutters, MD, PhD
role: Principal Investigator
affiliation: St. Antonius Hospital
facility: 
country: Netherlands
responsible party type: Sponsor-Investigator
investigator affiliation: St. Antonius Hospital
investigator full name: Human Adams
investigator title: Prof. Dr. D.H. Biesma
mesh term: Pneumonia
mesh term: Lung Diseases
mesh term: Lung Diseases, Interstitial
mesh term: Rituximab