<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/NCT04501939</url>
  </required_header>
  <id_info>
    <org_study_id>191407</org_study_id>
    <nct_id>NCT04501939</nct_id>
  </id_info>
  <brief_title>Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax</brief_title>
  <acronym>Venetoclax</acronym>
  <official_title>Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oncternal Therapeutics, Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Diego</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>
      Single center, open-label, phase 2 study to determine the efficacy of cirmtuzumab&#xD;
      consolidation in patients with measurable disease on venetoclax.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 2 study to test whether cirmtuzumab in combination with venetoclax given as&#xD;
      consolidation therapy can decrease the number of cancer cells that may be left in the bone&#xD;
      marrow or in the blood in patients who have been treated with venetoclax for at least one&#xD;
      year. Consolidation therapy is given after initial cancer treatment to further reduce the&#xD;
      number of cancer cells that may be left in the body. Cirmtuzumab, a monoclonal antibody that&#xD;
      inhibits receptor tyrosine kinase like orphan receptor (ROR1) signaling and stemness, may be&#xD;
      effective in reducing the risk of disease progression in patients with detectable minimal&#xD;
      residual disease (MRD) after treatment with venetoclax.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 6, 2020</start_date>
  <completion_date type="Anticipated">July 22, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 22, 2025</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>Cancer response to treatment</measure>
    <time_frame>6-24 months</time_frame>
    <description>Percentage of subjects with undetectable measurable residual disease after 6 months of cirmtuzumab + venetoclax treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of adverse events</measure>
    <time_frame>9-15 months</time_frame>
    <description>Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to next CLL treatment.</measure>
    <time_frame>9-24 months</time_frame>
    <description>Measurement of time of anti-cancer activity</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in gene expression in leukemic cells</measure>
    <time_frame>9-15 months</time_frame>
    <description>The change in gene expression of leukemia cells by single cell PCR or RNA after treatment with cirmtuzumab, including analysis of archival pre-venetoclax sample, when available.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">16</enrollment>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>Cirmtuzumab + Venetoclax</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients will receive a minimum of 6 cycles (cycle = 28 days) of therapy with venetoclax and cirmtuzumab during the treatment period. For patients who achieve undetectable minimal residual disease (uMRD) positive after cycle 6, an additional 6 cycles of venetoclax and cirmtuzumab may be administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cirmtuzumab</intervention_name>
    <description>Cycle 1, Day 1 &amp; 15 - 600mg Cycle 2, Day 1 to Cycle 6, Day 1 - 600mg</description>
    <arm_group_label>Cirmtuzumab + Venetoclax</arm_group_label>
    <other_name>Zilovertamab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venetoclax</intervention_name>
    <description>Venetoclax 400mg PO daily from cycle 1 day 1 for 6 cycles of 28 days.</description>
    <arm_group_label>Cirmtuzumab + Venetoclax</arm_group_label>
    <other_name>VENCLEXTA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must have detectable CLL/SLL (&gt; 0.01% leukemia cells present)&#xD;
&#xD;
          -  Must have received at least 12 months of venetoclax.&#xD;
&#xD;
          -  Patients may be receiving venetoclax at the time of screening and study entry.&#xD;
&#xD;
          -  Patients who have discontinued venetoclax more than 6 months prior to study entry must&#xD;
             still have a disease burden meeting criteria for low risk of TLS (i.e. no lymph node&#xD;
             greater than 5 cm in diameter; absolute lymphocyte count less than 25 k/uL)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Evidence of other clinically significant uncontrolled condition(s) including, but not&#xD;
        limited to:&#xD;
&#xD;
          -  Uncontrolled and/or active systemic infection (viral, bacterial or fungal)&#xD;
&#xD;
          -  Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note:&#xD;
             subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface&#xD;
             (HBs) antigen negative, anti-HBs antibody positive and anti-hepatitis B core (HBc)&#xD;
             antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins&#xD;
             (IVIG) may participate.&#xD;
&#xD;
          -  Child class B or C cirrhosis&#xD;
&#xD;
        Treatment with any of the following within 7 days prior to the first dose of cirmtuzumab:&#xD;
&#xD;
          -  Steroid therapy for anti-neoplastic intent&#xD;
&#xD;
          -  Biologic agent (monoclonal antibody) within 30 days for anti-neoplastic intent.&#xD;
&#xD;
          -  Chemotherapy (purine analog or alkylating agent) or target small molecule agent within&#xD;
             14 days or 5 half-lives (whichever is shorter), or has not recovered to less than&#xD;
             CTCAE grade 2 clinically significant adverse effect(s)/toxicity(s) of previous&#xD;
             therapy.&#xD;
&#xD;
          -  CLL therapy, aside from venetoclax.&#xD;
&#xD;
          -  History of other malignancy that could affect compliance with the protocol or&#xD;
             interpretation of results (example: patients with a history of curatively treated&#xD;
             basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are&#xD;
             generally eligible.)&#xD;
&#xD;
          -  Women who are pregnant or lactating&#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>Benjamin M Heyman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Diego</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Benjamin Heyman, MD</last_name>
    <phone>(858) 246-3038</phone>
    <email>bheyman@health.ucsd.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Betty Cabrera, MPH</last_name>
    <phone>858-534-5932</phone>
    <email>blcabrera@health.ucsd.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UCSD Koman Family Outpatient Pavilion</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elizabeth Miller</last_name>
      <phone>858-249-3000</phone>
      <email>eamiller@ucsd.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>February 28, 2023</last_update_submitted>
  <last_update_submitted_qc>February 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Benjamin Heyman</investigator_full_name>
    <investigator_title>Assistant Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>chronic lymphocytic leukemia</keyword>
  <keyword>CLL</keyword>
  <keyword>cirmtuzumab</keyword>
  <keyword>venetoclax</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Venetoclax</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04501939
org study id: 191407
nct id: NCT04501939
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Single center, open-label, phase 2 study to determine the efficacy of cirmtuzumab
      consolidation in patients with measurable disease on venetoclax.
This is a phase 2 study to test whether cirmtuzumab in combination with venetoclax given as
      consolidation therapy can decrease the number of cancer cells that may be left in the bone
      marrow or in the blood in patients who have been treated with venetoclax for at least one
      year. Consolidation therapy is given after initial cancer treatment to further reduce the
      number of cancer cells that may be left in the body. Cirmtuzumab, a monoclonal antibody that
      inhibits receptor tyrosine kinase like orphan receptor (ROR1) signaling and stemness, may be
      effective in reducing the risk of disease progression in patients with detectable minimal
      residual disease (MRD) after treatment with venetoclax.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cancer response to treatment
time frame: 6-24 months
description: Percentage of subjects with undetectable measurable residual disease after 6 months of cirmtuzumab + venetoclax treatment.
measure: Frequency of adverse events
time frame: 9-15 months
description: Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.
measure: Time to next CLL treatment.
time frame: 9-24 months
description: Measurement of time of anti-cancer activity
measure: Change in gene expression in leukemic cells
time frame: 9-15 months
description: The change in gene expression of leukemia cells by single cell PCR or RNA after treatment with cirmtuzumab, including analysis of archival pre-venetoclax sample, when available.
arm group label: Cirmtuzumab + Venetoclax
arm group type: Experimental
description: All patients will receive a minimum of 6 cycles (cycle = 28 days) of therapy with venetoclax and cirmtuzumab during the treatment period. For patients who achieve undetectable minimal residual disease (uMRD) positive after cycle 6, an additional 6 cycles of venetoclax and cirmtuzumab may be administered.
intervention type: Drug
intervention name: Cirmtuzumab
description: Cycle 1, Day 1 & 15 - 600mg Cycle 2, Day 1 to Cycle 6, Day 1 - 600mg
arm group label: Cirmtuzumab + Venetoclax
other name: Zilovertamab
intervention type: Drug
intervention name: Venetoclax
description: Venetoclax 400mg PO daily from cycle 1 day 1 for 6 cycles of 28 days.
arm group label: Cirmtuzumab + Venetoclax
other name: VENCLEXTA
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Benjamin M Heyman, MD
role: Principal Investigator
affiliation: University of California, San Diego
last name: Benjamin Heyman, MD
phone: (858) 246-3038
email: bheyman@health.ucsd.edu
last name: Betty Cabrera, MPH
phone: 858-534-5932
email: blcabrera@health.ucsd.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Diego
investigator full name: Benjamin Heyman
investigator title: Assistant Clinical Professor
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Venetoclax
sharing ipd: No