<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/NCT03013114</url>
  </required_header>
  <id_info>
    <org_study_id>ITP-Bortezomib</org_study_id>
    <nct_id>NCT03013114</nct_id>
  </id_info>
  <brief_title>A Single-center Clinical Trial of Bortezomib in Management of Immune Thrombocytopenia (ITP)</brief_title>
  <acronym>ITP</acronym>
  <official_title>A Single-center Clinical Trial of Bortezomib in Management of Immune Thrombocytopenia (ITP) With High Anti-platelet Antibodies Level</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shandong University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shandong University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary immune thrombocytopenia (ITP) is a disorder caused by autoantibody-mediated platelet&#xD;
      destruction and decreased platelet production. It has been reported that refractory ITP is&#xD;
      closely related to long-lived plasma cells (PCs), which are resistant to glucocorticoids,&#xD;
      conventional immunosuppressive and cytotoxic drugs, irradiation and B-cell depletion&#xD;
      therapies.&#xD;
&#xD;
      Proteasome inhibition bortezomib is one of the most promising therapeutic approaches to&#xD;
      target PCs, since this strategy has been shown to efficiently eliminate multiple myeloma&#xD;
      cells, that is, transformed PCs. It also has been successfully used in SLE-like mice,&#xD;
      experimental autoimmune MG rats and experimental hemophilia-A mice that develop anti-factor&#xD;
      VIII antibodies in preclinical models by depleting both short-lived and long-lived PCs.&#xD;
      Additionally, treatment with bortezomib resulted in a rapid clinical response in a patient&#xD;
      with refractory thrombotic thrombocytopenic purpura associated with the depletion of&#xD;
      inhibitory autoantibodies against ADAMTS13, a metalloproteinase that cleaves the von&#xD;
      Wille-brand factor, which is produced by plasma cells. Hence, the elimination of autoreactive&#xD;
      PCs by proteasome inhibitors might represent a new treatment strategy for&#xD;
      autoantibody-mediated diseases.&#xD;
&#xD;
      To date, refractory ITP is lacking of effective treatments and these findings encouraged us&#xD;
      to conduct a study of bortezomib in management of ITP with high anti-platelet antibodies&#xD;
      level. Data from this study may provide some idea of bortezomib in the treatment of ITP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators are undertaking a single-center, single-arm study of 20 primary ITP adult&#xD;
      patients from Shandong University Qilu Hospital&#xD;
&#xD;
      . All the participants are selected to receive bortezomib treatment (given intravenously at a&#xD;
      dose of 1.3mg/m2 on days 1,4,8,11). Platelet count, bleeding and other symptoms were&#xD;
      evaluated before and after treatment. Adverse events are also recorded throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_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>Platelet counts</measure>
    <time_frame>an average of 3 months</time_frame>
    <description>Complete response (CR)： A platelet count ≥ 100 * 10^9/L measured on two occasions &gt; 7 days apart and the absence of bleeding.&#xD;
Response (R)： A platelet count ≥ 30 * 10^9/L and a greater than two fold increase in platelet count from baseline measured on two occasions &gt; 7 days apart and the absence of bleeding.&#xD;
No response (NR)： A platelet count &lt; 30 * 10^9/L or a less than two fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on two occasions more than a day apart.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Numbers of Megakaryocyte Polyploidy</measure>
    <time_frame>6 days after every treatment cycle, an average of 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression rate of long-lived plasma cells</measure>
    <time_frame>6 days after every treatment cycle, an average of 3 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Immune Thrombocytopenia</condition>
  <arm_group>
    <arm_group_label>Bortezomib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bortezomib was given by intravenous bolus injection at a dose of 1.3 mg/m2 on days 1, 4, 8 and 11, repeated every 21 days. It will be given four cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <description>Bortezomib was given by intravenous bolus injection at a dose of 1.3 mg/m2 on days 1, 4, 8 and 11, repeated every 21 days. It will be given four cycles.</description>
    <arm_group_label>Bortezomib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  failure to achieve at least Response&#xD;
&#xD;
          -  need of treatment(s) (including, but not limited to, low dose of corticosteroids) to&#xD;
             minimize the risk of clinically significant bleeding. Need of on-demand or adjunctive&#xD;
             therapy alone does not qualify the patient as refractory&#xD;
&#xD;
          -  primary ITP confirmed by excluding other supervened causes of thrombocytopenia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  hypertension&#xD;
&#xD;
          -  cardiovascular disease&#xD;
&#xD;
          -  diabetes&#xD;
&#xD;
          -  liver and kidney function impairment&#xD;
&#xD;
          -  HCV, HIV, HBsAg seropositive status&#xD;
&#xD;
          -  patients with systemic lupus erythematosus and/or antiphospholipid syndrome&#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>Ming Hou</last_name>
    <role>Principal Investigator</role>
    <affiliation>Qilu Hospital, Shandong University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ming Hou</last_name>
    <email>houming@medmail.com.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shandong University Qilu hospital</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <zip>250012</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Hou Ming</last_name>
      <email>houming@medmail.com.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>January 5, 2017</last_update_submitted>
  <last_update_submitted_qc>January 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shandong University</investigator_affiliation>
    <investigator_full_name>Ming Hou</investigator_full_name>
    <investigator_title>Professor and Director</investigator_title>
  </responsible_party>
  <keyword>Bortezomib Immune thrombocytopenia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombocytopenia</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>Bortezomib</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/NCT03013114
org study id: ITP-Bortezomib
nct id: NCT03013114
lead sponsor: 
has dmc: Yes
Primary immune thrombocytopenia (ITP) is a disorder caused by autoantibody-mediated platelet
      destruction and decreased platelet production. It has been reported that refractory ITP is
      closely related to long-lived plasma cells (PCs), which are resistant to glucocorticoids,
      conventional immunosuppressive and cytotoxic drugs, irradiation and B-cell depletion
      therapies.

      Proteasome inhibition bortezomib is one of the most promising therapeutic approaches to
      target PCs, since this strategy has been shown to efficiently eliminate multiple myeloma
      cells, that is, transformed PCs. It also has been successfully used in SLE-like mice,
      experimental autoimmune MG rats and experimental hemophilia-A mice that develop anti-factor
      VIII antibodies in preclinical models by depleting both short-lived and long-lived PCs.
      Additionally, treatment with bortezomib resulted in a rapid clinical response in a patient
      with refractory thrombotic thrombocytopenic purpura associated with the depletion of
      inhibitory autoantibodies against ADAMTS13, a metalloproteinase that cleaves the von
      Wille-brand factor, which is produced by plasma cells. Hence, the elimination of autoreactive
      PCs by proteasome inhibitors might represent a new treatment strategy for
      autoantibody-mediated diseases.

      To date, refractory ITP is lacking of effective treatments and these findings encouraged us
      to conduct a study of bortezomib in management of ITP with high anti-platelet antibodies
      level. Data from this study may provide some idea of bortezomib in the treatment of ITP.
The investigators are undertaking a single-center, single-arm study of 20 primary ITP adult
      patients from Shandong University Qilu Hospital

      . All the participants are selected to receive bortezomib treatment (given intravenously at a
      dose of 1.3mg/m2 on days 1,4,8,11). Platelet count, bleeding and other symptoms were
      evaluated before and after treatment. Adverse events are also recorded throughout the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Platelet counts
time frame: an average of 3 months
description: Complete response (CR)： A platelet count ≥ 100 * 10^9/L measured on two occasions > 7 days apart and the absence of bleeding.
Response (R)： A platelet count ≥ 30 * 10^9/L and a greater than two fold increase in platelet count from baseline measured on two occasions > 7 days apart and the absence of bleeding.
No response (NR)： A platelet count < 30 * 10^9/L or a less than two fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on two occasions more than a day apart.
measure: Numbers of Megakaryocyte Polyploidy
time frame: 6 days after every treatment cycle, an average of 3 months
measure: Expression rate of long-lived plasma cells
time frame: 6 days after every treatment cycle, an average of 3 months
arm group label: Bortezomib
arm group type: Experimental
description: Bortezomib was given by intravenous bolus injection at a dose of 1.3 mg/m2 on days 1, 4, 8 and 11, repeated every 21 days. It will be given four cycles.
intervention type: Drug
intervention name: Bortezomib
description: Bortezomib was given by intravenous bolus injection at a dose of 1.3 mg/m2 on days 1, 4, 8 and 11, repeated every 21 days. It will be given four cycles.
arm group label: Bortezomib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Ming Hou
role: Principal Investigator
affiliation: Qilu Hospital, Shandong University
last name: Ming Hou
email: houming@medmail.com.cn
facility: 
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shandong University
investigator full name: Ming Hou
investigator title: Professor and Director
mesh term: Thrombocytopenia
mesh term: Purpura, Thrombocytopenic, Idiopathic
mesh term: Bortezomib