<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/NCT04465760</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00018976</org_study_id>
    <secondary_id>NCI-2020-02554</secondary_id>
    <secondary_id>STUDY00018976</secondary_id>
    <secondary_id>R01HL151367</secondary_id>
    <nct_id>NCT04465760</nct_id>
  </id_info>
  <brief_title>Xisomab 3G3 for the Prevention of Catheter-Associated Thrombosis in Patients With Cancer Receiving Chemotherapy</brief_title>
  <official_title>A Phase II Study of Xisomab 3G3, a Monoclonal Antibody Preventing the Activation of FXI by FXIIa, for the Prophylaxis of Catheter-Associated Thrombosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OHSU Knight Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>OHSU Knight Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well xisomab 3G3 works in preventing catheter-associated&#xD;
      blood clots (thrombosis) in patients with cancer receiving chemotherapy. Many patients with&#xD;
      cancer develop blood clots from their catheters and can have pain, swelling, and other&#xD;
      symptoms. They also often require blood thinners, which can increase the risk of bleeding.&#xD;
      Xisomab 3G3 is type of drug called a monoclonal antibody that may prevent blood clots caused&#xD;
      by a catheter in patients receiving chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE I. To determine the efficacy of xisomab as measured by the incidence of&#xD;
      catheter-associated thrombosis (CAT) in individuals with a central venous catheter.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the safety and tolerability of xisomab 3G3 in cancer patients with a PICC or&#xD;
      indwelling catheter.&#xD;
&#xD;
      EXPLORATORY OBJECTIVE:&#xD;
&#xD;
      I. Assessment of drug exposure and catheter occlusions leading to medical intervention.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive xisomab 3G3 intravenously (IV) or via catheter within 48 hours of catheter&#xD;
      placement. Patients then receive standard of care chemotherapy 2 days later. After&#xD;
      approximately 2 weeks, patients undergo standard of care ultrasound for possible CAT.&#xD;
&#xD;
      After completion of study, patients are followed up for 60 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 25, 2021</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of catheter-associated thrombosis (CAT)</measure>
    <time_frame>Up to end of treatment visit (day 18)</time_frame>
    <description>The incidence of overall CAT (inclusive of both symptomatic and asymptomatic events) will be assessed and reported with 95% confidence interval.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of major and clinically-relevant bleeding</measure>
    <time_frame>Up to end of follow-up (60 days from time of administration)</time_frame>
    <description>Bleeding will be defined using the International Society of Thrombosis and Hemostasis definition of major bleeding for clinical investigations of anti-hemostatic medicinal products in nonsurgical patients (i.e., fatal bleeding, critical organ bleeding such as central nervous system bleeding, or bleeding causing a fall in hemoglobin of 20 g/L or more) and clinically relevant non-major bleeding (i.e., bleeding that does not fit the former definition of major bleeding but prompts medical attention). The incidence of major and clinically relevant non-major bleeding, along with 95% confidence interval, will be assessed using the safety analysis set (all patients who are exposed to the single dose of study drug).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of xisomab 3G3-associated adverse events (AEs)</measure>
    <time_frame>Up to end of follow-up (60 days from time of administration)</time_frame>
    <description>Descriptive statistics of safety will be presented using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 using the safety analysis set (all patients who are exposed to the single dose of study drug). All on-study AEs, treatment-related AEs, serious adverse events (SAEs), and treatment-related SAEs will be tabulated using worst grade per National Cancer Institute (NCI) CTCAE v5.0 criteria by system organ class and preferred term. On-study lab parameters including hematology, chemistry, liver function, and renal function will be summarized using worst grade NCI CTCAE v5.0 criteria.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Quantification of coagulation measures: platelet count</measure>
    <time_frame>Up to end of treatment visit (day 18)</time_frame>
    <description>Presented with descriptive statistics.</description>
  </other_outcome>
  <other_outcome>
    <measure>Quantification of coagulation measures: Prothrombin time/international normalized ratio (PT/INR)</measure>
    <time_frame>Up to end of treatment visit (day 18)</time_frame>
    <description>Presented with descriptive statistics.</description>
  </other_outcome>
  <other_outcome>
    <measure>Quantification of coagulation measures: Activated partial thromboplastin time (aPTT)</measure>
    <time_frame>Up to end of treatment visit (day 18)</time_frame>
    <description>Presented with descriptive statistics.</description>
  </other_outcome>
  <other_outcome>
    <measure>Xisomab 3G3 pharmacokinetics</measure>
    <time_frame>Up to end of treatment visit (day 18)</time_frame>
    <description>Presented with descriptive statistics.</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to detection of thrombosis</measure>
    <time_frame>From xisomab 3G3 infusion up to end of treatment visit (day 18)</time_frame>
    <description>Will be reported for those (expected few) subjects with symptomatic CAT.</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to clot symptoms</measure>
    <time_frame>From xisomab 3G3 infusion up to end of treatment visit (day 18)</time_frame>
    <description>Will be reported for those (expected few) subjects with symptomatic CAT.</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of patients that had a catheter occlusion requiring medical intervention</measure>
    <time_frame>Up to end of treatment visit (day 18)</time_frame>
    <description>Results will be presented with descriptive statistics.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Lymphoma</condition>
  <condition>Malignant Solid Neoplasm</condition>
  <condition>Plasma Cell Myeloma</condition>
  <arm_group>
    <arm_group_label>Supportive Care (xisomab 3G3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive xisomab 3G3 IV or via catheter within 48 hours of catheter placement. Patients then receive standard of care chemotherapy 2 days later. After approximately 2 weeks, patients undergo standard of care ultrasound for possible CAT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Xisomab 3G3</intervention_name>
    <description>Given IV or via catheter</description>
    <arm_group_label>Supportive Care (xisomab 3G3)</arm_group_label>
    <other_name>AB 023</other_name>
    <other_name>AB-023</other_name>
    <other_name>AB023</other_name>
    <other_name>Anti-factor XI Monoclonal Antibody Xisomab 3G3</other_name>
    <other_name>Anti-FXI Antibody Xisomab 3G3</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant or legally authorized representative (LAR) must provide written informed&#xD;
             consent before any study-specific procedures or interventions are performed&#xD;
&#xD;
          -  In consultation with principal investigator (PI) and treating physician, participant's&#xD;
             cancer-directed therapy allows for a 1-day period between administration of study drug&#xD;
             and subsequent start of planned cancer-directed therapy&#xD;
&#xD;
          -  Individuals with a confirmed solid malignancy that are scheduled to undergo insertion&#xD;
             of a PICC line or indwelling central venous catheter as part of planned anticancer&#xD;
             therapy per institutional standards&#xD;
&#xD;
          -  Must have Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2&#xD;
&#xD;
          -  Platelet count &gt; 100 x 10^9/L&#xD;
&#xD;
          -  Female participants of childbearing potential must have a negative urine or serum&#xD;
             pregnancy test within 72 hours prior to receiving the first dose of study medication.&#xD;
             If the urine test is positive or cannot be confirmed as negative, a serum pregnancy&#xD;
             test will be required. Participants of childbearing potential are defined as any&#xD;
             female who has experienced menarche and who has not undergone surgical sterilization&#xD;
             (hysterectomy or bilateral oophorectomy) and is not postmenopausal&#xD;
&#xD;
          -  Female participants of childbearing potential must agree to use adequate methods of&#xD;
             contraception starting with the first dose of study therapy through 90 days after the&#xD;
             last dose of study therapy. Participants of childbearing potential are those who have&#xD;
             not been surgically sterilized or have not been free from menses for &gt; 1 year without&#xD;
             an alternative medical cause&#xD;
&#xD;
          -  Male participants must agree to use an adequate method of contraception starting with&#xD;
             the first dose of study therapy through 90 days after the last dose of study therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Actively receiving treatment in another therapeutic clinical trial&#xD;
&#xD;
          -  Active acute leukemia (lymphoma and myeloma are allowed)&#xD;
&#xD;
          -  At time of enrollment, known contraindication to anticoagulation therapy, including:&#xD;
&#xD;
               -  Clinically significant active bleeding&#xD;
&#xD;
               -  Individual is within 72 hours of major surgery&#xD;
&#xD;
               -  Abnormal baseline coagulation tests, including international normalized ratio&#xD;
                  (INR) &gt; 1.5, or activated partial thromboplastin time (aPTT) prolonged&#xD;
&#xD;
               -  Abnormal renal function defined by an estimated glomerular filtration rate (eGFR)&#xD;
                  &lt; 45 mL/min&#xD;
&#xD;
               -  Abnormal hepatic function defined as liver function tests (LFTs) (aspartate&#xD;
                  aminotransferase [AST], alanine aminotransferase [ALT] or total bilirubin) &gt; 2 x&#xD;
                  the upper limit of normal or known Child-Pugh class B or C cirrhosis&#xD;
&#xD;
               -  Prior history of intracranial hemorrhage&#xD;
&#xD;
               -  Primary brain tumors or known brain metastasis&#xD;
&#xD;
               -  Major extracranial bleed within the last 6 months where the cause has not been&#xD;
                  identified or treated&#xD;
&#xD;
               -  Known bleeding diathesis&#xD;
&#xD;
               -  Use of therapeutic anticoagulation or anti-platelet agents for any indication at&#xD;
                  enrollment&#xD;
&#xD;
               -  At the discretion of the investigator, any other contraindication to&#xD;
                  anticoagulation therapy&#xD;
&#xD;
               -  Presence of a pediatric-sized PICC line&#xD;
&#xD;
               -  Participant is expected to receive chemotherapy associated with a 15% or higher&#xD;
                  incidence of grade 3-4 thrombocytopenia within 14 days of receiving study drug&#xD;
&#xD;
          -  Preexisting intravenous catheter, or indwelling spinal or epidural catheter, at time&#xD;
             of enrollment that is intended to remain for the duration of study. Participants may&#xD;
             remain eligible if existing catheter is to be removed before placement of a catheter&#xD;
             for cancer directed therapy. Removal of existing catheter should occur at least 24&#xD;
             hours prior to PICC or indwelling catheter insertion&#xD;
&#xD;
          -  Previously documented hypersensitivity to either the drug or excipients&#xD;
&#xD;
          -  Psychiatric illness/social situations, or any other condition, that in the opinion of&#xD;
             the investigator, would limit compliance with study requirements&#xD;
&#xD;
          -  Participant is pregnant or breastfeeding, or expecting to conceive or father children&#xD;
             within the projected duration of the trial, starting with the screening visit through&#xD;
             90 days after the last dose of trial treatment&#xD;
&#xD;
          -  Participant is allergic to heparin or heparin derivatives&#xD;
&#xD;
          -  Participants with a history of venous thromboembolism within the last 3 months&#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>Joseph Shatzel, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>OHSU Knight Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>OHSU Knight Cancer Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joseph J. Shatzel, M.D.</last_name>
      <phone>503-494-6594</phone>
      <email>shatzel@ohsu.edu</email>
    </contact>
    <investigator>
      <last_name>Joseph J. Shatzel, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>October 10, 2022</last_update_submitted>
  <last_update_submitted_qc>October 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>OHSU Knight Cancer Institute</investigator_affiliation>
    <investigator_full_name>Joseph Shatzel M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</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/NCT04465760
org study id: STUDY00018976
secondary id: NCI-2020-02554
secondary id: STUDY00018976
secondary id: R01HL151367
nct id: NCT04465760
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well xisomab 3G3 works in preventing catheter-associated
      blood clots (thrombosis) in patients with cancer receiving chemotherapy. Many patients with
      cancer develop blood clots from their catheters and can have pain, swelling, and other
      symptoms. They also often require blood thinners, which can increase the risk of bleeding.
      Xisomab 3G3 is type of drug called a monoclonal antibody that may prevent blood clots caused
      by a catheter in patients receiving chemotherapy.
PRIMARY OBJECTIVE I. To determine the efficacy of xisomab as measured by the incidence of
      catheter-associated thrombosis (CAT) in individuals with a central venous catheter.

      SECONDARY OBJECTIVE:

      I. To evaluate the safety and tolerability of xisomab 3G3 in cancer patients with a PICC or
      indwelling catheter.

      EXPLORATORY OBJECTIVE:

      I. Assessment of drug exposure and catheter occlusions leading to medical intervention.

      OUTLINE:

      Patients receive xisomab 3G3 intravenously (IV) or via catheter within 48 hours of catheter
      placement. Patients then receive standard of care chemotherapy 2 days later. After
      approximately 2 weeks, patients undergo standard of care ultrasound for possible CAT.

      After completion of study, patients are followed up for 60 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Incidence of catheter-associated thrombosis (CAT)
time frame: Up to end of treatment visit (day 18)
description: The incidence of overall CAT (inclusive of both symptomatic and asymptomatic events) will be assessed and reported with 95% confidence interval.
measure: Incidence of major and clinically-relevant bleeding
time frame: Up to end of follow-up (60 days from time of administration)
description: Bleeding will be defined using the International Society of Thrombosis and Hemostasis definition of major bleeding for clinical investigations of anti-hemostatic medicinal products in nonsurgical patients (i.e., fatal bleeding, critical organ bleeding such as central nervous system bleeding, or bleeding causing a fall in hemoglobin of 20 g/L or more) and clinically relevant non-major bleeding (i.e., bleeding that does not fit the former definition of major bleeding but prompts medical attention). The incidence of major and clinically relevant non-major bleeding, along with 95% confidence interval, will be assessed using the safety analysis set (all patients who are exposed to the single dose of study drug).
measure: Incidence of xisomab 3G3-associated adverse events (AEs)
time frame: Up to end of follow-up (60 days from time of administration)
description: Descriptive statistics of safety will be presented using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 using the safety analysis set (all patients who are exposed to the single dose of study drug). All on-study AEs, treatment-related AEs, serious adverse events (SAEs), and treatment-related SAEs will be tabulated using worst grade per National Cancer Institute (NCI) CTCAE v5.0 criteria by system organ class and preferred term. On-study lab parameters including hematology, chemistry, liver function, and renal function will be summarized using worst grade NCI CTCAE v5.0 criteria.
measure: Quantification of coagulation measures: platelet count
time frame: Up to end of treatment visit (day 18)
description: Presented with descriptive statistics.
measure: Quantification of coagulation measures: Prothrombin time/international normalized ratio (PT/INR)
time frame: Up to end of treatment visit (day 18)
description: Presented with descriptive statistics.
measure: Quantification of coagulation measures: Activated partial thromboplastin time (aPTT)
time frame: Up to end of treatment visit (day 18)
description: Presented with descriptive statistics.
measure: Xisomab 3G3 pharmacokinetics
time frame: Up to end of treatment visit (day 18)
description: Presented with descriptive statistics.
measure: Time to detection of thrombosis
time frame: From xisomab 3G3 infusion up to end of treatment visit (day 18)
description: Will be reported for those (expected few) subjects with symptomatic CAT.
measure: Time to clot symptoms
time frame: From xisomab 3G3 infusion up to end of treatment visit (day 18)
description: Will be reported for those (expected few) subjects with symptomatic CAT.
measure: Proportion of patients that had a catheter occlusion requiring medical intervention
time frame: Up to end of treatment visit (day 18)
description: Results will be presented with descriptive statistics.
arm group label: Supportive Care (xisomab 3G3)
arm group type: Experimental
description: Patients receive xisomab 3G3 IV or via catheter within 48 hours of catheter placement. Patients then receive standard of care chemotherapy 2 days later. After approximately 2 weeks, patients undergo standard of care ultrasound for possible CAT.
intervention type: Drug
intervention name: Xisomab 3G3
description: Given IV or via catheter
arm group label: Supportive Care (xisomab 3G3)
other name: AB 023
other name: AB-023
other name: AB023
other name: Anti-factor XI Monoclonal Antibody Xisomab 3G3
other name: Anti-FXI Antibody Xisomab 3G3
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joseph Shatzel, M.D.
role: Principal Investigator
affiliation: OHSU Knight Cancer Institute
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: OHSU Knight Cancer Institute
investigator full name: Joseph Shatzel M.D.
investigator title: Principal Investigator
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Thrombosis
mesh term: Antibodies
mesh term: Immunoglobulins