<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/NCT01696474</url>
  </required_header>
  <id_info>
    <org_study_id>CAD0111</org_study_id>
    <secondary_id>EudraCT number 2011-006329-42</secondary_id>
    <nct_id>NCT01696474</nct_id>
  </id_info>
  <brief_title>Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease</brief_title>
  <acronym>CAD0111</acronym>
  <official_title>Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gruppo Italiano Malattie EMatologiche dell'Adulto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gruppo Italiano Malattie EMatologiche dell'Adulto</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This multicenter, phase II, open label study will enroll patients with chronic cold&#xD;
      agglutinin disorder. A single course of Bortezomib will be given at the dose of 1,3 mg/sqm iv&#xD;
      on days 1, 4, 8, 11.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Based on its activity in MM, single agent Bortezomib was tested in phase II trials in&#xD;
      lymphoplasmacytic lymphoma, the disorder most frequently associated with CAD, and achieved&#xD;
      40-80% responses. These striking clinical responses indicate that proteasome activity is&#xD;
      critical for the survival of immunoglobulin-secreting cells. The resolution of transfusion&#xD;
      requirement in two patients with refractory CAD associated with IgMk monoclonal gammopathy&#xD;
      has been reported after treatment with a short course of Bortezomib. It may be interesting to&#xD;
      test the efficacy of Bortezomib in a larger series of patients with refractory CAD,&#xD;
      idiopathic or associated with an otherwise asymptomatic B cell clonal disorder, and to&#xD;
      evaluate the duration of clinical benefit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">March 27, 2017</completion_date>
  <primary_completion_date type="Actual">March 27, 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>Number of patients who become transfusion-free after Bortezomib therapy.</measure>
    <time_frame>After 3 months from study entry.</time_frame>
    <description>Cumulative proportion of patients transfusion-free at three months after Bortezomib therapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients who have never been transfused with a &gt;2g hemoglobin rise compared to baseline.</measure>
    <time_frame>After 3 months from study entry.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of CTC grade 3 and 4 adverse events.</measure>
    <time_frame>After 12 months from study entry.</time_frame>
    <description>Evaluation of the incidence of CTC grade 3 and 4 adverse events during and after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration in months of transfusion independence.</measure>
    <time_frame>At 12 months from study entry.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of treatment on the underlying clonal B cell disorder.</measure>
    <time_frame>At 3 months from study entry.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Refractory Cold Agglutinin Disease</condition>
  <arm_group>
    <arm_group_label>Bortezomib therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single course of Bortezomib will be given at the dose of 1,3 mg/sqm iv on days 1, 4, 8, 11. Prophylaxis of HZ reactivation will be given with oral acyclovir at the dosage of 400 mg twice daily for one month after the end of Bortezomib.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <arm_group_label>Bortezomib therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with chronic cold agglutinin disorder requiring or with a hemoglobin&#xD;
             concentration below 10g/L determined at least monthly during the two months before&#xD;
             entering the trial;&#xD;
&#xD;
          -  Failure of at least one previous treatment attempt;&#xD;
&#xD;
          -  Hemoglobin level assessment;&#xD;
&#xD;
          -  Presence of serum cold agglutinin (CA). If an overnight incubation is used for CA&#xD;
             detection, a titer at 4°C of 64 or higher is required;&#xD;
&#xD;
          -  Written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of a concomitant lymphoproliferative disorder requiring specific treatment&#xD;
             for reasons other than cold agglutinin related hemolytic anemia;&#xD;
&#xD;
          -  Preexisting peripheral neuropathy;&#xD;
&#xD;
          -  Known hypersensitivity to Bortezomib;&#xD;
&#xD;
          -  Non-cooperative behaviour or non-compliance;&#xD;
&#xD;
          -  Psychiatric diseases or conditions that might impair the ability to give informed&#xD;
             consent;&#xD;
&#xD;
          -  Patients who are pregnant (women of childbearing potential must have a negative serum&#xD;
             pregnancy test). Post-menopausal women must be amenorrhoic for at least 24 months to&#xD;
             be considered of non-childbearing potential. Male and female patients must agree to&#xD;
             employ an effective barrier method of birth control throughout the study and for up to&#xD;
             3 months following discontinuation of study drug.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giuseppe Rossi, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>S.C. Ematologia e Dipartimento di Oncologia Medica Spedali Civili - Brescia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria</name>
      <address>
        <city>Foggia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cattedra di Ematologia CTMO Università degli Studi di Parma</name>
      <address>
        <city>Parma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U.O. Ematologia Clinica - Azienda USL di Pescara</name>
      <address>
        <city>Pescara</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Bianchi Melacrino Morelli</name>
      <address>
        <city>Reggio Calabria</city>
        <zip>89100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università degli Studi &quot;Sapienza&quot; - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Ematologica - Policlinico Universitario</name>
      <address>
        <city>Udine</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Bortolo</name>
      <address>
        <city>Vicenza</city>
        <zip>36100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 27, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2012</study_first_posted>
  <last_update_submitted>October 26, 2017</last_update_submitted>
  <last_update_submitted_qc>October 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Refractory cold agglutinin disease</keyword>
  <keyword>Bortezomib</keyword>
  <keyword>blood-transfusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Hemolytic, Autoimmune</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bortezomib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>November 9, 2017</submitted>
    <returned>August 10, 2018</returned>
    <submitted>August 11, 2018</submitted>
    <returned>January 24, 2019</returned>
    <submitted>February 5, 2019</submitted>
    <returned>May 14, 2019</returned>
  </pending_results>
  <!-- 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/NCT01696474
org study id: CAD0111
secondary id: EudraCT number 2011-006329-42
nct id: NCT01696474
lead sponsor: 
has dmc: No
This multicenter, phase II, open label study will enroll patients with chronic cold
      agglutinin disorder. A single course of Bortezomib will be given at the dose of 1,3 mg/sqm iv
      on days 1, 4, 8, 11.
Based on its activity in MM, single agent Bortezomib was tested in phase II trials in
      lymphoplasmacytic lymphoma, the disorder most frequently associated with CAD, and achieved
      40-80% responses. These striking clinical responses indicate that proteasome activity is
      critical for the survival of immunoglobulin-secreting cells. The resolution of transfusion
      requirement in two patients with refractory CAD associated with IgMk monoclonal gammopathy
      has been reported after treatment with a short course of Bortezomib. It may be interesting to
      test the efficacy of Bortezomib in a larger series of patients with refractory CAD,
      idiopathic or associated with an otherwise asymptomatic B cell clonal disorder, and to
      evaluate the duration of clinical benefit.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients who become transfusion-free after Bortezomib therapy.
time frame: After 3 months from study entry.
description: Cumulative proportion of patients transfusion-free at three months after Bortezomib therapy.
measure: Number of patients who have never been transfused with a >2g hemoglobin rise compared to baseline.
time frame: After 3 months from study entry.
measure: Number of CTC grade 3 and 4 adverse events.
time frame: After 12 months from study entry.
description: Evaluation of the incidence of CTC grade 3 and 4 adverse events during and after treatment.
measure: Duration in months of transfusion independence.
time frame: At 12 months from study entry.
measure: Effect of treatment on the underlying clonal B cell disorder.
time frame: At 3 months from study entry.
arm group label: Bortezomib therapy
arm group type: Experimental
description: A single course of Bortezomib will be given at the dose of 1,3 mg/sqm iv on days 1, 4, 8, 11. Prophylaxis of HZ reactivation will be given with oral acyclovir at the dosage of 400 mg twice daily for one month after the end of Bortezomib.
intervention type: Drug
intervention name: Bortezomib
arm group label: Bortezomib therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Giuseppe Rossi, Dr.
role: Principal Investigator
affiliation: S.C. Ematologia e Dipartimento di Oncologia Medica Spedali Civili - Brescia
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Anemia, Hemolytic, Autoimmune
mesh term: Bortezomib
sharing ipd: No
submitted: November 9, 2017
returned: August 10, 2018
submitted: August 11, 2018
returned: January 24, 2019
submitted: February 5, 2019
returned: May 14, 2019