<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/NCT03797261</url>
  </required_header>
  <id_info>
    <org_study_id>M16-785</org_study_id>
    <secondary_id>2018-003314-41</secondary_id>
    <nct_id>NCT03797261</nct_id>
  </id_info>
  <brief_title>A Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies</brief_title>
  <official_title>Phase 1b Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>AbbVie</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This dose-escalation study evaluating the safety, pharmacokinetics and preliminary efficacy&#xD;
      of venetoclax in combination with AMG 176 in participants with relapsed or refractory acute&#xD;
      myeloid leukemia (AML) and participants with Non-Hodgkin's lymphoma (NHL)/diffuse large&#xD;
      B-cell lymphoma (DLBCL).&#xD;
&#xD;
      This study will include a dose escalation phase to identify the maximum tolerated&#xD;
      dose/recommended phase 2 dose (MTD/RPTD) of venetoclax plus AMG 176 as well as a dose&#xD;
      expansion phase to confirm safety, explore efficacy, and confirm the suitability of the&#xD;
      preliminary RPTD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Safety&#xD;
  </why_stopped>
  <start_date type="Actual">March 18, 2019</start_date>
  <completion_date type="Actual">December 30, 2019</completion_date>
  <primary_completion_date type="Actual">December 30, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176</measure>
    <time_frame>Up to 28 days after first dose of study drug in a dose-escalation phase</time_frame>
    <description>The MTD and/or RPTD of venetoclax and of AMG 176 will be determined during the dose escalation phase of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>From first dose of study drug until 30 days or 5 half-lives after discontinuation of study drug administration will be collected (up to approximately 4 years).</time_frame>
    <description>An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composite Complete Remission Rate (CRc) for Participants with AML</measure>
    <time_frame>Up to approximately 2 years from last subject first dose</time_frame>
    <description>CRc rate is defined as CR + CRi (CR with incomplete blood count recovery).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) for Participants with AML</measure>
    <time_frame>Up to approximately 2 years from last subject first dose</time_frame>
    <description>ORR is defined as the percentage of participants with documented partial response (PR) or better (CR + CRi + partial response [PR]) based on International Working Group (IWG) criteria for AML</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR for Participants with NHL</measure>
    <time_frame>Up to approximately 2 years from last subject first dose</time_frame>
    <description>ORR is defined as the percentage of participants with documented CR + PR based on Lugano criteria for NHL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Venetoclax</measure>
    <time_frame>Up to approximately 28 days after first dose of study drug</time_frame>
    <description>Maximum observed plasma concentration (Cmax) of venetoclax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax</measure>
    <time_frame>Up to approximately 28 days after first dose of study drug</time_frame>
    <description>Time to maximum plasma concentration (Tmax) of Venetoclax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of Venetoclax</measure>
    <time_frame>Up to approximately 28 days after first dose of study drug</time_frame>
    <description>Area under the plasma concentration-time curve (AUC) of venetoclax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of AMG 176</measure>
    <time_frame>Up to approximately 16 days after first dose of study drug</time_frame>
    <description>Maximum observed plasma concentration (Cmax) of AMG 176</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life (t1/2) of AMG 176</measure>
    <time_frame>Approximately 16 days after first dose of study drug</time_frame>
    <description>Terminal phase elimination half-life (t1/2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of AMG 176</measure>
    <time_frame>Approximately 16 days after first dose of study drug</time_frame>
    <description>Area Under the Plasma Concentration-time Curve (AUC) of AMG 176</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL) of AMG 176</measure>
    <time_frame>Approximately 16 days after first dose of study drug</time_frame>
    <description>Clearance (CL) is defined the volume of plasma cleared of the drug per unit time.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Non-Hodgkin's Lymphoma</condition>
  <condition>Diffuse Large B-cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Venetoclax + AMG 176</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venetoclax</intervention_name>
    <description>tablet, oral</description>
    <arm_group_label>Venetoclax + AMG 176</arm_group_label>
    <other_name>ABT-199</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AMG 176</intervention_name>
    <description>solution, intravenous</description>
    <arm_group_label>Venetoclax + AMG 176</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adequate kidney, liver and hematology values as described in the protocol.&#xD;
&#xD;
          -  Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML) or R/R&#xD;
             Non-Hodgkin's lymphoma (NHL)/diffuse large B-cell lymphoma (DLBCL) confirmed by the&#xD;
             World Health Organization (WHO) criteria, as appropriate.&#xD;
&#xD;
          -  Meets the following disease activity criteria:&#xD;
&#xD;
          -  AML: must have received at least 1 prior therapy for AML and be ineligible for&#xD;
             cytotoxic therapy and allogeneic stem cell transplant.&#xD;
&#xD;
          -  NHL/DLBCL: measurable disease with a bidimensional lesion measuring at least 1.5 cm;&#xD;
             received at least 1 prior therapy for NHL with no curative treatment option as&#xD;
             determined by the investigator and be ineligible for a stem cell transplant.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of clinically significant medical condition that, in the opinion of the&#xD;
             investigator, would adversely affect participation in this study.&#xD;
&#xD;
          -  History of of any malignancy within the last 6 months except for those specified in&#xD;
             this protocol and low-grade malignancies not requiring active treatment such as&#xD;
             non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostate cancer in&#xD;
             situ.&#xD;
&#xD;
          -  Prior allogeneic stem cell transplant or autologous stem cell transplant within 100&#xD;
             days of study drug administration and no signs or symptoms of acute or chronic&#xD;
             graft-versus-host disease.&#xD;
&#xD;
          -  Previous enrollment in a randomized trial including either venetoclax or AMG 176.&#xD;
&#xD;
          -  Known active or chronic pancreatitis; severe chronic obstructive pulmonary disease&#xD;
             with hypoxemia; central nervous system manifestations of malignancy.&#xD;
&#xD;
          -  Active, uncontrolled infection.&#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>ABBVIE INC.</last_name>
    <role>Study Director</role>
    <affiliation>AbbVie</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope /ID# 207393</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC Norris Cancer Center /ID# 207396</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics /ID# 207459</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univ Kansas Med Ctr /ID# 207480</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duplicate_Dana-Farber Cancer Institute /ID# 207367</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University-School of Medicine /ID# 206995</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone Medical Center /ID# 207390</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016-6402</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unc /Id# 207388</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Ctr /ID# 208482</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Calvary Mater Newcastle /ID# 211455</name>
      <address>
        <city>Waratah</city>
        <state>New South Wales</state>
        <zip>2298</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital /ID# 210602</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alfred Health /ID# 210350</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Frankfurt /ID# 207984</name>
      <address>
        <city>Frankfurt am Main</city>
        <state>Hessen</state>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Leipzig /ID# 209824</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 207987</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 207803</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207788</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Germany</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.rxabbvie.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>December 3, 2021</last_update_submitted>
  <last_update_submitted_qc>December 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute Myeloid Leukemia</keyword>
  <keyword>Non-Hodgkin's Lymphoma</keyword>
  <keyword>Cancer</keyword>
  <keyword>Venetoclax</keyword>
  <keyword>AMG 176</keyword>
  <keyword>diffuse large B-cell lymphoma (DLBCL)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Hematologic Neoplasms</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/NCT03797261
org study id: M16-785
secondary id: 2018-003314-41
nct id: NCT03797261
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This dose-escalation study evaluating the safety, pharmacokinetics and preliminary efficacy
      of venetoclax in combination with AMG 176 in participants with relapsed or refractory acute
      myeloid leukemia (AML) and participants with Non-Hodgkin's lymphoma (NHL)/diffuse large
      B-cell lymphoma (DLBCL).

      This study will include a dose escalation phase to identify the maximum tolerated
      dose/recommended phase 2 dose (MTD/RPTD) of venetoclax plus AMG 176 as well as a dose
      expansion phase to confirm safety, explore efficacy, and confirm the suitability of the
      preliminary RPTD.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176
time frame: Up to 28 days after first dose of study drug in a dose-escalation phase
description: The MTD and/or RPTD of venetoclax and of AMG 176 will be determined during the dose escalation phase of the study.
measure: Number of Participants With Adverse Events
time frame: From first dose of study drug until 30 days or 5 half-lives after discontinuation of study drug administration will be collected (up to approximately 4 years).
description: An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
measure: Composite Complete Remission Rate (CRc) for Participants with AML
time frame: Up to approximately 2 years from last subject first dose
description: CRc rate is defined as CR + CRi (CR with incomplete blood count recovery).
measure: Objective Response Rate (ORR) for Participants with AML
time frame: Up to approximately 2 years from last subject first dose
description: ORR is defined as the percentage of participants with documented partial response (PR) or better (CR + CRi + partial response [PR]) based on International Working Group (IWG) criteria for AML
measure: ORR for Participants with NHL
time frame: Up to approximately 2 years from last subject first dose
description: ORR is defined as the percentage of participants with documented CR + PR based on Lugano criteria for NHL.
measure: Maximum Plasma Concentration (Cmax) of Venetoclax
time frame: Up to approximately 28 days after first dose of study drug
description: Maximum observed plasma concentration (Cmax) of venetoclax.
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
time frame: Up to approximately 28 days after first dose of study drug
description: Time to maximum plasma concentration (Tmax) of Venetoclax.
measure: AUC of Venetoclax
time frame: Up to approximately 28 days after first dose of study drug
description: Area under the plasma concentration-time curve (AUC) of venetoclax.
measure: Maximum Plasma Concentration (Cmax) of AMG 176
time frame: Up to approximately 16 days after first dose of study drug
description: Maximum observed plasma concentration (Cmax) of AMG 176
measure: Half-life (t1/2) of AMG 176
time frame: Approximately 16 days after first dose of study drug
description: Terminal phase elimination half-life (t1/2)
measure: AUC of AMG 176
time frame: Approximately 16 days after first dose of study drug
description: Area Under the Plasma Concentration-time Curve (AUC) of AMG 176
measure: Clearance (CL) of AMG 176
time frame: Approximately 16 days after first dose of study drug
description: Clearance (CL) is defined the volume of plasma cleared of the drug per unit time.
arm group label: Venetoclax + AMG 176
arm group type: Experimental
description: Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored.
intervention type: Drug
intervention name: Venetoclax
description: tablet, oral
arm group label: Venetoclax + AMG 176
other name: ABT-199
intervention type: Drug
intervention name: AMG 176
description: solution, intravenous
arm group label: Venetoclax + AMG 176
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: ABBVIE INC.
role: Study Director
affiliation: AbbVie
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Germany
country: United States
url: http://www.rxabbvie.com
description: Related Info
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Hematologic Neoplasms
mesh term: Venetoclax
sharing ipd: No