<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/NCT02260414</url>
  </required_header>
  <id_info>
    <org_study_id>1408049</org_study_id>
    <secondary_id>2014-000946-31</secondary_id>
    <nct_id>NCT02260414</nct_id>
  </id_info>
  <brief_title>Effects of Anticoagulant Preventive Injection in Patients With Blood Cancer</brief_title>
  <acronym>METRO B</acronym>
  <official_title>Effects of Injection Tinzaparin Prophylactic Dose (4,500 IU Anti-Xa) on Thrombin Generation in Patients With Multiple Myeloma, Lymphoma Patients and Patients Hospitalized for an Acute Medical Condition.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Saint Etienne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>LEO Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Saint Etienne</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In cancer, the incidence of venous thromboembolism (VTE) is particularly high in patients&#xD;
      with myeloma, especially when it is de novo and treated with thalidomide, lenalidomide or&#xD;
      erythropoietin. Curiously, the prevention of VTE with LMWH (low-molecular-weight heparin) in&#xD;
      myeloma seems no more effective than that achieved with aspirin, while the effectiveness of&#xD;
      the latter in the primary prevention of VTE has never been demonstrated regardless of the&#xD;
      type of population considered. Meanwhile, a biological study showed that prophylactic doses&#xD;
      of LMWH in patients with different types of cancer did not always optimal reduction of&#xD;
      thrombin peak during the 24 hours following the injection of LMWH. These clinical and&#xD;
      biological studies lead to the conclusion that patients with myeloma may be resistant to the&#xD;
      usual doses of preventive LMWH, which may explain the failure of prevention.&#xD;
&#xD;
      Initially we intend to investigate whether this resistance to prophylactic doses of LMWH is&#xD;
      present in patient's biology and if this resistance is specific to myeloma in hematological&#xD;
      cancers. For this, we propose to study the evolution of thrombin generation by&#xD;
      Thrombinography during 24 hours after subcutaneous injection of 4500 anti-Xa IU Tinzaparin in&#xD;
      6 patients with de novo myeloma whit high thrombo embolic risk ie treated with thalidomide,&#xD;
      lenalidomide or erythropoietin. LMWH is Tinzaparin chosen because it does not accumulate in&#xD;
      patients with impaired renal function, and has a greater anti-biological activity thrombotic&#xD;
      than other LMWH.&#xD;
&#xD;
      To assess whether the observed pattern of thrombin generation is particularly multiple&#xD;
      myeloma, we will take the same study in 6 patients with aggressive lymphoma and 6 medical&#xD;
      patients hospitalized for acute heart and respiratory failure.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 14, 2015</start_date>
  <completion_date type="Actual">May 9, 2017</completion_date>
  <primary_completion_date type="Actual">May 9, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endogenous Thrombin Potential (ETP, nM.min) for all patients with de novo myeloma with high thrombotic risk</measure>
    <time_frame>hours : 0, 3, 8, 18, 24</time_frame>
    <description>Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Endogenous Thrombin Potential (ETP, nM.min) for all patients with aggressive lymphoma treated with chemotherapy</measure>
    <time_frame>hours : 0, 3, 8, 18, 24</time_frame>
    <description>Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endogenous Thrombin Potential (ETP, nM.min) for all patients with over 40 years hospitalized for heart or respiratory failure</measure>
    <time_frame>hours : 0, 3, 8, 18, 24</time_frame>
    <description>Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences of Endogenous Thrombin Potential (ETP, nM.min) between group 1 and group 2 et 3</measure>
    <time_frame>hours : 0, 3, 8, 18, 24</time_frame>
    <description>Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Lymphoma</condition>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Patients with multiple myeloma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient with multiple myeloma indication with de novo standard treatment thalidomide or lenalidomide or erythropoietin treated with one injection of 4500 IU tinzaparin and blood samples taken at hours : 0, 3, 8, 18 and 24 after subcutaneous injection of tinzaparin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with agressive lymphoma</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient hospitalized for aggressive lymphoma treated with chemotherapy treated with one injection of 4500 IU tinzaparin and blood samples taken at hours : 0, 3, 8, 18 and 24 after subcutaneous injection of tinzaparin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with acute medical condition</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient older than 40 years and hospitalized at least three days for an acute medical pathology type of acute respiratory or cardiac treated with one injection of 4500 IU tinzaparin and blood samples taken at hours : 0, 3, 8, 18 and 24 after subcutaneous injection of tinzaparin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tinzaparin</intervention_name>
    <description>single subcutaneous injection of 4500 IU tinzaparin</description>
    <arm_group_label>Patients with acute medical condition</arm_group_label>
    <arm_group_label>Patients with agressive lymphoma</arm_group_label>
    <arm_group_label>Patients with multiple myeloma</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood sample</intervention_name>
    <description>blood sample taken at hours 0, 3, 8, 18 and 24 after subcutaneous injection of 4500 IU tinzaparin</description>
    <arm_group_label>Patients with acute medical condition</arm_group_label>
    <arm_group_label>Patients with agressive lymphoma</arm_group_label>
    <arm_group_label>Patients with multiple myeloma</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Body weight between 40 and 100 kg&#xD;
&#xD;
          2. Patient:&#xD;
&#xD;
        2a- With multiple myeloma indication with de novo standard treatment thalidomide or&#xD;
        lenalidomide or erythropoietin (group 1) 2b- Or hospitalized for aggressive lymphoma&#xD;
        treated with chemotherapy (group 2) 2c- Or older than 40 years and hospitalized at least&#xD;
        three days for an acute medical pathology type of acute respiratory or cardiac (group 3)&#xD;
        decompensation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient requiring anticoagulant therapy at curative doses&#xD;
&#xD;
          -  Patients with a lower platelet count 80 G / L&#xD;
&#xD;
          -  Subject with a history of heparin-induced thrombocytopenia&#xD;
&#xD;
          -  Subject with a history of hemorrhagic disease&#xD;
&#xD;
          -  History of severe trauma within 6 weeks prior to enrollment&#xD;
&#xD;
          -  Organic lesion at risk of bleeding&#xD;
&#xD;
          -  Poor renal with creatinine clearance &lt;30 ml / min&#xD;
&#xD;
          -  Hypersensitivity to Tinzaparin&#xD;
&#xD;
          -  Events or bleeding tendencies associated with coagulation disorders&#xD;
&#xD;
          -  Subject on oral anticoagulant&#xD;
&#xD;
          -  For group 3: Presence of hematological malignancy or active cancer&#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>Bernard TARDY, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU SAINT-ETIENNE</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Saint-Etienne</name>
      <address>
        <city>Saint-Etienne</city>
        <zip>42055</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <last_update_submitted>May 10, 2017</last_update_submitted>
  <last_update_submitted_qc>May 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Endogenous Thrombin Potential</keyword>
  <keyword>Lymphoma</keyword>
  <keyword>Multiple Myeloma</keyword>
  <keyword>tinzaparin</keyword>
  <keyword>thrombin generation</keyword>
  <keyword>Thromboplastin generation tests</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tinzaparin</mesh_term>
    <mesh_term>Heparin, Low-Molecular-Weight</mesh_term>
    <mesh_term>Dalteparin</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/NCT02260414
org study id: 1408049
secondary id: 2014-000946-31
nct id: NCT02260414
lead sponsor: 
collaborator: 
has dmc: No
In cancer, the incidence of venous thromboembolism (VTE) is particularly high in patients
      with myeloma, especially when it is de novo and treated with thalidomide, lenalidomide or
      erythropoietin. Curiously, the prevention of VTE with LMWH (low-molecular-weight heparin) in
      myeloma seems no more effective than that achieved with aspirin, while the effectiveness of
      the latter in the primary prevention of VTE has never been demonstrated regardless of the
      type of population considered. Meanwhile, a biological study showed that prophylactic doses
      of LMWH in patients with different types of cancer did not always optimal reduction of
      thrombin peak during the 24 hours following the injection of LMWH. These clinical and
      biological studies lead to the conclusion that patients with myeloma may be resistant to the
      usual doses of preventive LMWH, which may explain the failure of prevention.

      Initially we intend to investigate whether this resistance to prophylactic doses of LMWH is
      present in patient's biology and if this resistance is specific to myeloma in hematological
      cancers. For this, we propose to study the evolution of thrombin generation by
      Thrombinography during 24 hours after subcutaneous injection of 4500 anti-Xa IU Tinzaparin in
      6 patients with de novo myeloma whit high thrombo embolic risk ie treated with thalidomide,
      lenalidomide or erythropoietin. LMWH is Tinzaparin chosen because it does not accumulate in
      patients with impaired renal function, and has a greater anti-biological activity thrombotic
      than other LMWH.

      To assess whether the observed pattern of thrombin generation is particularly multiple
      myeloma, we will take the same study in 6 patients with aggressive lymphoma and 6 medical
      patients hospitalized for acute heart and respiratory failure.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Endogenous Thrombin Potential (ETP, nM.min) for all patients with de novo myeloma with high thrombotic risk
time frame: hours : 0, 3, 8, 18, 24
description: Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin
measure: Endogenous Thrombin Potential (ETP, nM.min) for all patients with aggressive lymphoma treated with chemotherapy
time frame: hours : 0, 3, 8, 18, 24
description: Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin
measure: Endogenous Thrombin Potential (ETP, nM.min) for all patients with over 40 years hospitalized for heart or respiratory failure
time frame: hours : 0, 3, 8, 18, 24
description: Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin
measure: Differences of Endogenous Thrombin Potential (ETP, nM.min) between group 1 and group 2 et 3
time frame: hours : 0, 3, 8, 18, 24
description: Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin
arm group label: Patients with multiple myeloma
arm group type: Experimental
description: Patient with multiple myeloma indication with de novo standard treatment thalidomide or lenalidomide or erythropoietin treated with one injection of 4500 IU tinzaparin and blood samples taken at hours : 0, 3, 8, 18 and 24 after subcutaneous injection of tinzaparin
arm group label: Patients with agressive lymphoma
arm group type: Active Comparator
description: Patient hospitalized for aggressive lymphoma treated with chemotherapy treated with one injection of 4500 IU tinzaparin and blood samples taken at hours : 0, 3, 8, 18 and 24 after subcutaneous injection of tinzaparin
arm group label: Patients with acute medical condition
arm group type: Active Comparator
description: Patient older than 40 years and hospitalized at least three days for an acute medical pathology type of acute respiratory or cardiac treated with one injection of 4500 IU tinzaparin and blood samples taken at hours : 0, 3, 8, 18 and 24 after subcutaneous injection of tinzaparin
intervention type: Drug
intervention name: Tinzaparin
description: single subcutaneous injection of 4500 IU tinzaparin
arm group label: Patients with acute medical condition
arm group label: Patients with agressive lymphoma
arm group label: Patients with multiple myeloma
intervention type: Other
intervention name: Blood sample
description: blood sample taken at hours 0, 3, 8, 18 and 24 after subcutaneous injection of 4500 IU tinzaparin
arm group label: Patients with acute medical condition
arm group label: Patients with agressive lymphoma
arm group label: Patients with multiple myeloma
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bernard TARDY, PhD
role: Principal Investigator
affiliation: CHU SAINT-ETIENNE
facility: 
country: France
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Tinzaparin
mesh term: Heparin, Low-Molecular-Weight
mesh term: Dalteparin