<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/NCT01713738</url>
  </required_header>
  <id_info>
    <org_study_id>CHB 02-12-160</org_study_id>
    <secondary_id>Genentec/IDEC U2591S</secondary_id>
    <secondary_id>Glaser 435</secondary_id>
    <nct_id>NCT01713738</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Rituximab in Children and Adolescents With Chronic Idiopathic Thrombocytopenic Purpura (ITP)</brief_title>
  <official_title>Open Label, Phase I/II Trial of Rituximab for Chronic, Severe Idiopathic Thrombocytopenic Purpura (ITP)in Children and Adolescents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neufeld, Ellis J, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Biogen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Glaser Pediatric Research Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Terrana ITP Research Fund</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Neufeld, Ellis J, MD, PhD</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate the safety and efficacy of rituximab in children ages&#xD;
      18 months to 18 years, who have severe, chronic ITP. Eligible patients with either primary or&#xD;
      secondary ITP are treated with rituximab once a week for 4 doses, and then followed for up to&#xD;
      one year. Response is defined as having a platelet count greater than or equal to 50,000/mL&#xD;
      on four consecutive weekly measures beginning anytime in weeks 9 - 12.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this open label, phase I/II study is to evaluate the safety and efficacy of&#xD;
      rituximab in children ages 18 months to 18 years, who have severe, chronic ITP. Eligible&#xD;
      patients with either primary or secondary ITP are treated with rituximab once a week for 4&#xD;
      doses, and then followed for up to one year. The primary and secondary objectives for safety&#xD;
      and efficacy are as follows:&#xD;
&#xD;
      Primary&#xD;
&#xD;
        1. Efficacy: To evaluate the effectiveness of rituximab in severe or refractory pediatric&#xD;
           ITP, with response defined as follows: platelet count greater than or equal to 50,000/mL&#xD;
           on four consecutive weekly measures beginning anytime in weeks 9 - 12 (day 57 - day 84),&#xD;
           with the first and fourth measure being spaced at least 22 days apart (i.e., once&#xD;
           established during the 9 - 12 week timeframe, the response would be defined as beginning&#xD;
           at the first one of these measures). All measurements must be independent of supportive&#xD;
           care, as follows: 1) no IVIG (intravenous immunoglobulin) administration within 7 days&#xD;
           of the first measure or at any time between measures, 2) no initiation of a 4-day&#xD;
           corticosteroid &quot;pulse&quot; within 7 days of the first measure or at any time between&#xD;
           measures, 3) no RHo (D) immunoglobulin (WinRHo-SDFTM ) administration within 7 days of&#xD;
           the first measure or at any time between measures, and 4) no platelet transfusions&#xD;
           administered within 7 days of the first measure or at any time between measures.&#xD;
&#xD;
        2. Safety: To obtain further safety information on rituximab in this clinical setting using&#xD;
           Genentech standard safety monitoring and SAE reporting. In addition, the frequency of&#xD;
           hypogammaglobulinemia will be assessed as the incidence of IgG levels &lt;1/2 the lower&#xD;
           limit of normal for age.&#xD;
&#xD;
      Secondary&#xD;
&#xD;
        1. To evaluate the one-year clinical course of severe or refractory ITP patients treated&#xD;
           with a single course of rituximab. What fraction of responsive patients maintains this&#xD;
           response?&#xD;
&#xD;
        2. To assess the need for salvage therapy (supportive care) in this severely affected group&#xD;
           of patients during the clinical trial.&#xD;
&#xD;
        3. To evaluate the rate of &quot;early response,&quot; defined as: platelets greater than or equal to&#xD;
           50,000/mL at least one week off rescue therapy, BEFORE day 57, and continuing for four&#xD;
           consecutive weeks.&#xD;
&#xD;
        4. To follow the trend of bleeding scores from onset of therapy through the duration of the&#xD;
           trial.&#xD;
&#xD;
        5. To assess the incidence of hypogammaglobulinemia requiring intervention (IgG level &lt;1/2&#xD;
           of lower limit of normal for age) in this setting. IVIG 400 mg/kg monthly will be used&#xD;
           to treat hypogammaglobulinemia.&#xD;
&#xD;
        6. To describe the health-related quality of life (HRQL) of children with severe or&#xD;
           refractory ITP, based on parent report and to assess the impact on the family, using&#xD;
           standardized questionnaires. This is a pilot-scale objective.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2003</start_date>
  <completion_date type="Actual">December 2005</completion_date>
  <primary_completion_date type="Actual">December 2005</primary_completion_date>
  <phase>Phase 1/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>platelet levels</measure>
    <time_frame>9 - 12 weeks after 1st dose of rituximab</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>hypogammaglobulinemia</measure>
    <time_frame>over one year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>fraction of responsive patients maintaining response over 1 year</measure>
    <time_frame>week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>assessment of need for salvage therapy</measure>
    <time_frame>first 12 weeks of trial</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rate of early response before day 57</measure>
    <time_frame>before day 57, and 4 additional weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>trend of bleeding scores throughout trial</measure>
    <time_frame>over one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>description of health-related quality of life</measure>
    <time_frame>over one year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Idiopathic Thrombocytopenic Purpura (ITP)</condition>
  <condition>Immune Thrombocytopenic Purpura (ITP)</condition>
  <arm_group>
    <arm_group_label>rituximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rituximab</intervention_name>
    <description>infusion of 4 weekly doses of 375 mg/m2 rituximab</description>
    <arm_group_label>rituximab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        severe, chronic ITP, including refractory; at least 6 months from diagnosis for refractory;&#xD;
        at least 12 months from diagnosis for severe; platelet counts &lt;10,000/mm3 twice in past 3&#xD;
        months without bleeding; platelet counts &lt;20,000/mm3 twice in past 3 months with bleeding&#xD;
&#xD;
        -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        ever had B or T cell neoplasm; HIV/AIDS; allergy to murine antibodies; treatment with&#xD;
        investigational immunosuppressive strategies within past 3 months -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Months</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ellis J Neufeld, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Boston Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA, Mattel Children's Hospital</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University School of Medicine</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University School of Medicine</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Boston</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Van Eslander Cancer Center, St. John Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Medical College at Cornell University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwestern Medical Center at Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <last_update_submitted>November 8, 2012</last_update_submitted>
  <last_update_submitted_qc>November 8, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 9, 2012</last_update_posted>
  <responsible_party>
    <name_title>Ellis J. Neufeld, MD, PhD</name_title>
    <organization>Children's Hospital Boston</organization>
  </responsible_party>
  <keyword>ITP</keyword>
  <keyword>rituximab</keyword>
  <keyword>bleeding score</keyword>
  <keyword>platelet count</keyword>
  <keyword>health-related quality of life</keyword>
  <keyword>HRQL</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Purpura</mesh_term>
    <mesh_term>Purpura, Thrombocytopenic</mesh_term>
    <mesh_term>Purpura, Thrombocytopenic, Idiopathic</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/NCT01713738
org study id: CHB 02-12-160
secondary id: Genentec/IDEC U2591S
secondary id: Glaser 435
nct id: NCT01713738
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of the study is to evaluate the safety and efficacy of rituximab in children ages
      18 months to 18 years, who have severe, chronic ITP. Eligible patients with either primary or
      secondary ITP are treated with rituximab once a week for 4 doses, and then followed for up to
      one year. Response is defined as having a platelet count greater than or equal to 50,000/mL
      on four consecutive weekly measures beginning anytime in weeks 9 - 12.
The purpose of this open label, phase I/II study is to evaluate the safety and efficacy of
      rituximab in children ages 18 months to 18 years, who have severe, chronic ITP. Eligible
      patients with either primary or secondary ITP are treated with rituximab once a week for 4
      doses, and then followed for up to one year. The primary and secondary objectives for safety
      and efficacy are as follows:

      Primary

        1. Efficacy: To evaluate the effectiveness of rituximab in severe or refractory pediatric
           ITP, with response defined as follows: platelet count greater than or equal to 50,000/mL
           on four consecutive weekly measures beginning anytime in weeks 9 - 12 (day 57 - day 84),
           with the first and fourth measure being spaced at least 22 days apart (i.e., once
           established during the 9 - 12 week timeframe, the response would be defined as beginning
           at the first one of these measures). All measurements must be independent of supportive
           care, as follows: 1) no IVIG (intravenous immunoglobulin) administration within 7 days
           of the first measure or at any time between measures, 2) no initiation of a 4-day
           corticosteroid "pulse" within 7 days of the first measure or at any time between
           measures, 3) no RHo (D) immunoglobulin (WinRHo-SDFTM ) administration within 7 days of
           the first measure or at any time between measures, and 4) no platelet transfusions
           administered within 7 days of the first measure or at any time between measures.

        2. Safety: To obtain further safety information on rituximab in this clinical setting using
           Genentech standard safety monitoring and SAE reporting. In addition, the frequency of
           hypogammaglobulinemia will be assessed as the incidence of IgG levels <1/2 the lower
           limit of normal for age.

      Secondary

        1. To evaluate the one-year clinical course of severe or refractory ITP patients treated
           with a single course of rituximab. What fraction of responsive patients maintains this
           response?

        2. To assess the need for salvage therapy (supportive care) in this severely affected group
           of patients during the clinical trial.

        3. To evaluate the rate of "early response," defined as: platelets greater than or equal to
           50,000/mL at least one week off rescue therapy, BEFORE day 57, and continuing for four
           consecutive weeks.

        4. To follow the trend of bleeding scores from onset of therapy through the duration of the
           trial.

        5. To assess the incidence of hypogammaglobulinemia requiring intervention (IgG level <1/2
           of lower limit of normal for age) in this setting. IVIG 400 mg/kg monthly will be used
           to treat hypogammaglobulinemia.

        6. To describe the health-related quality of life (HRQL) of children with severe or
           refractory ITP, based on parent report and to assess the impact on the family, using
           standardized questionnaires. This is a pilot-scale objective.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: platelet levels
time frame: 9 - 12 weeks after 1st dose of rituximab
measure: hypogammaglobulinemia
time frame: over one year
measure: fraction of responsive patients maintaining response over 1 year
time frame: week 52
measure: assessment of need for salvage therapy
time frame: first 12 weeks of trial
measure: rate of early response before day 57
time frame: before day 57, and 4 additional weeks
measure: trend of bleeding scores throughout trial
time frame: over one year
measure: description of health-related quality of life
time frame: over one year
arm group label: rituximab
arm group type: Experimental
intervention type: Drug
intervention name: rituximab
description: infusion of 4 weekly doses of 375 mg/m2 rituximab
arm group label: rituximab
criteria: 
gender: All
minimum age: 18 Months
maximum age: 18 Years
healthy volunteers: No
last name: Ellis J Neufeld, MD, PhD
role: Principal Investigator
affiliation: Boston Children's Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
name title: Ellis J. Neufeld, MD, PhD
organization: Children's Hospital Boston
mesh term: Purpura
mesh term: Purpura, Thrombocytopenic
mesh term: Purpura, Thrombocytopenic, Idiopathic
mesh term: Rituximab