<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/NCT01702038</url>
  </required_header>
  <id_info>
    <org_study_id>DAIT ALE01</org_study_id>
    <nct_id>NCT01702038</nct_id>
  </id_info>
  <brief_title>Determining the Responses and Impact of Rituximab-instigated Cell Depletion on T Cells in People With SLE</brief_title>
  <official_title>Rituximab in SLE: Understanding of Long-term Responses and the Impact of B Cell Depletion on T Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine how B cell subsets and autoantibodies are related&#xD;
      to disease remission after rituximab treatment in subjects with Systemic Lupus Erythematosus&#xD;
      (SLE).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Immune cells are an important part of the abnormal autoimmune response in SLE. The B cell is&#xD;
      a significant part of this autimmune response because it produces the antibodies which can&#xD;
      react with normal tissue of the body. B cells have the ability to accumulate and promote the&#xD;
      development of SLE. The purpose of this study is to determine how B cell subsets and&#xD;
      autoantibodies are related to disease remission after rituximab treatment in subjects with&#xD;
      SLE.&#xD;
&#xD;
      This study will last approximately two years and consist of 15 study visits. These visits&#xD;
      will occur at screening, baseline, Days 0 and 14, and Months 1, 2, 3, 4, 6, 9, 12, 15, 18,&#xD;
      21, and 24. Participants will receive a single rituximab injection on Days 0 and 14.&#xD;
      Medication history and blood tests will occur at every study visit. A physical exam, medical&#xD;
      history, and urine tests will occur at most visits. For females, a pregnancy test will occur&#xD;
      at selected visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <start_date>September 2009</start_date>
  <phase>Phase 2</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>Ratio of B and T cell subsets among those with and without a long-term response and those with and without baseline anti-RBP antibody</measure>
    <time_frame>Day 0 through month 24</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Impact of prolonged B cell absence on the composition and activation status of helper T cell subsets and regulatory T cells</measure>
    <time_frame>Day 0 through month 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of B cell depletion on interferon-alpha activity</measure>
    <time_frame>Day 0 through month 24</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Lupus Erythematosus, Systemic</condition>
  <arm_group>
    <arm_group_label>Rituximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive an intravenous infusion of rituximab on Days 0 and 14</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>1000 mg administered intravenously</description>
    <arm_group_label>Rituximab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of SLE&#xD;
&#xD;
          -  Positive ANA with a titer of at least 1:160&#xD;
&#xD;
          -  Active disease (one or more modified BILAG A or B) or inability to lower steroids to&#xD;
             leass than 20 mg/day. More information about this criterion can be found in the&#xD;
             protocol.&#xD;
&#xD;
          -  For females, must agree to use effective birth control methods for the duration of the&#xD;
             study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe thrombocytopenia&#xD;
&#xD;
          -  Active, moderate, or severe proliferative glomerulonephritis&#xD;
&#xD;
          -  Active CNS manifestations due to lupus other than migraines, mild cognitive&#xD;
             dysfunction, or mood disorders. More information about this criterion can be found in&#xD;
             the protocol.&#xD;
&#xD;
          -  Poorly controlled anti-phospholipid syndrom&#xD;
&#xD;
          -  Significant organ dysfunction&#xD;
&#xD;
          -  Conditions, other than SLE, that are likely to require prolonged systemic steroids&#xD;
&#xD;
          -  Chronic infections. More information about this criterion can be found in the&#xD;
             protocol.&#xD;
&#xD;
          -  Hepatitis B infection&#xD;
&#xD;
          -  Hepatitis C infection&#xD;
&#xD;
          -  Deep space infection within two years of study entry&#xD;
&#xD;
          -  Severe bacterial infection within three months of study entry&#xD;
&#xD;
          -  More than one severe bacterial infection within two years of study entry&#xD;
&#xD;
          -  Positive purified protein derivative tuberculin skin test&#xD;
&#xD;
          -  History of cancer, not including basal cell carcinomas and carcinoma in situ of the&#xD;
             cervix with documentation of successful treatment&#xD;
&#xD;
          -  Alcohol or drug abuse&#xD;
&#xD;
          -  Surgery within three months of study entry&#xD;
&#xD;
          -  Immunization with a live vaccine within two months of study entry&#xD;
&#xD;
          -  Any immunization within one month of study entry&#xD;
&#xD;
          -  Received cyclophosphamide or calcineurin inhibitors within six months of study entry&#xD;
&#xD;
          -  Received anti-TNF alpha antibody within 3 months of study entry&#xD;
&#xD;
          -  Received etanercept within one month of study entry&#xD;
&#xD;
          -  Received anti-CD20 antibodies or other lymphocyte depleting antibodies&#xD;
&#xD;
          -  Received Immunoglobin G infusion protein or monoclonal antibody&#xD;
&#xD;
          -  Treatment with FDA non-approved agents within six months of study entry&#xD;
&#xD;
          -  Transaminases greater than two times the upper limit of normal&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ignacio Sanz, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Rochester</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John Looney, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Rochester</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Eisenberg R. Targeting B cells in SLE: the experience with rituximab treatment (anti-CD20). Endocr Metab Immune Disord Drug Targets. 2006 Dec;6(4):345-50. doi: 10.2174/187153006779025757.</citation>
    <PMID>17214580</PMID>
  </reference>
  <reference>
    <citation>Pego-Reigosa JM, Isenberg DA. Systemic lupus erythematosus: pharmacological developments and recommendations for a therapeutic strategy. Expert Opin Investig Drugs. 2008 Jan;17(1):31-41. doi: 10.1517/13543784.17.1.31.</citation>
    <PMID>18095917</PMID>
  </reference>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <last_update_submitted>October 4, 2012</last_update_submitted>
  <last_update_submitted_qc>October 4, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 8, 2012</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>Lupus Erythematosus, Systemic</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/NCT01702038
org study id: DAIT ALE01
nct id: NCT01702038
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine how B cell subsets and autoantibodies are related
      to disease remission after rituximab treatment in subjects with Systemic Lupus Erythematosus
      (SLE).
Immune cells are an important part of the abnormal autoimmune response in SLE. The B cell is
      a significant part of this autimmune response because it produces the antibodies which can
      react with normal tissue of the body. B cells have the ability to accumulate and promote the
      development of SLE. The purpose of this study is to determine how B cell subsets and
      autoantibodies are related to disease remission after rituximab treatment in subjects with
      SLE.

      This study will last approximately two years and consist of 15 study visits. These visits
      will occur at screening, baseline, Days 0 and 14, and Months 1, 2, 3, 4, 6, 9, 12, 15, 18,
      21, and 24. Participants will receive a single rituximab injection on Days 0 and 14.
      Medication history and blood tests will occur at every study visit. A physical exam, medical
      history, and urine tests will occur at most visits. For females, a pregnancy test will occur
      at selected visits.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Ratio of B and T cell subsets among those with and without a long-term response and those with and without baseline anti-RBP antibody
time frame: Day 0 through month 24
measure: Impact of prolonged B cell absence on the composition and activation status of helper T cell subsets and regulatory T cells
time frame: Day 0 through month 24
measure: Effect of B cell depletion on interferon-alpha activity
time frame: Day 0 through month 24
arm group label: Rituximab
arm group type: Experimental
description: Participants will receive an intravenous infusion of rituximab on Days 0 and 14
intervention type: Drug
intervention name: Rituximab
description: 1000 mg administered intravenously
arm group label: Rituximab
criteria: 
gender: All
minimum age: 19 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ignacio Sanz, MD
role: Study Chair
affiliation: University of Rochester
last name: John Looney, MD
role: Study Chair
affiliation: University of Rochester
facility: 
facility: 
country: United States
citation: Eisenberg R. Targeting B cells in SLE: the experience with rituximab treatment (anti-CD20). Endocr Metab Immune Disord Drug Targets. 2006 Dec;6(4):345-50. doi: 10.2174/187153006779025757.
PMID: 17214580
citation: Pego-Reigosa JM, Isenberg DA. Systemic lupus erythematosus: pharmacological developments and recommendations for a therapeutic strategy. Expert Opin Investig Drugs. 2008 Jan;17(1):31-41. doi: 10.1517/13543784.17.1.31.
PMID: 18095917
responsible party type: Sponsor
mesh term: Lupus Erythematosus, Systemic
mesh term: Rituximab