<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/NCT03298516</url>
  </required_header>
  <id_info>
    <org_study_id>GO39902</org_study_id>
    <nct_id>NCT03298516</nct_id>
  </id_info>
  <brief_title>A Study of DCLL9718S in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or DCLL9718S in Combination With Azacitidine in Participants With Previously Untreated AML Unsuitable for Intensive Induction Chemotherapy</brief_title>
  <official_title>An Open-Label, Phase I, Dose-Escalation Study Evaluating the Safety and Tolerability of DCLL9718S in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or DCLL9718S in Combination With Azacitidine in Patients With Previously Untreated AML Unsuitable for Intensive Induction Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Genentech, Inc.</source>
  <oversight_info>
    <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 Ia/Ib, open-label, multicenter study will evaluate the safety, tolerability, and&#xD;
      preliminary efficacy of DCLL9718S as a single agent (Phase Ia, Arm A) in participants with&#xD;
      relapsed or refractory AML or in combination with azacitidine (Phase Ib, Arm B) in&#xD;
      participants with previously untreated AML who are not eligible for intensive induction&#xD;
      chemotherapy. Each arm will consist of two stages: a dose-escalation stage and an expansion&#xD;
      stage. The dose-escalation stage is designed to establish the maximum tolerated dose (MTD)&#xD;
      and recommended Phase II dose (RP2D) for DCLL9718S alone (Arm A) or in combination with&#xD;
      azacitidine (Arm B). The dose-expansion stage is designed to characterize the long-term&#xD;
      safety and tolerability of DCLL9718S.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 15, 2017</start_date>
  <completion_date type="Actual">July 16, 2019</completion_date>
  <primary_completion_date type="Actual">July 16, 2019</primary_completion_date>
  <phase>Phase 1</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of participants With Adverse Events (AEs)</measure>
    <time_frame>Baseline up to end of study (up to approximately 3 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Dose-Limiting Toxicities (DLTs)</measure>
    <time_frame>Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>MTD of DCLL9718S</measure>
    <time_frame>Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>RP2D of DCLL9718S</measure>
    <time_frame>Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of DCLL9718S</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of Azacitidine</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-Time Curve (AUC) of DCLL9718S</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration Observed (Cmax) of DCLL9718S</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Clearance of DCLL9718S</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-Life (t1/2) of DCLL9718S</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution Under Steady-State (Vss) of DCLL9718S</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Complete Remission (CR), CR With Incomplete Blood Count Recovery (CRi), CR With Incomplete Platelet Count Recovery (CRp), and Overall Response, Assessed as per International Working Group (IWG) Criteria</measure>
    <time_frame>From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response, Assessed as per IWG Criteria</measure>
    <time_frame>From the date of first response to the earliest recurrence or disease progression (up to approximately 3 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From the date of first treatment to the date of death from any cause (up to approximately 3 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-Free Survival (EFS), Assessed as per IWG Criteria</measure>
    <time_frame>From the date of first treatment until treatment failure, relapsed from CR, CRp, or CRi, or death from any cause, whichever occurs first (up to approximately 3 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS), Assessed as per IWG Criteria</measure>
    <time_frame>From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S</measure>
    <time_frame>Baseline up to end of study (up to approximately 3 years)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Leukemia, Myeloid, Acute</condition>
  <arm_group>
    <arm_group_label>Arm A: DCLL9718S</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive escalating doses of DCLL9718S intravenously (IV) in each 21-day cycle to determine MTD and RP2D in dose-escalation stage followed by DCLL9718S IV at RP2D in each 21-day cycle in dose-expansion stage until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: DCLL9718S and Azacitidine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive escalating doses of DCLL9718S (starting dose: at least one dose level below a completed and tolerated DCLL9718S monotherapy in Arm A) IV in each 28-day cycle and azacitidine 75 milligrams per square meter (mg/m^2) subcutaneously (SC) or IV on Days 1-7 of each 28-day cycle to determine MTD and RP2D of DCLL9718S in dose-escalation stage followed by DCLL9718S IV at RP2D in each 28-day cycle and azacitidine 75 mg/m^2 SC or IV on Days 1-7 of each 28-day cycle in dose-expansion stage until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. Azacitidine may also be given on Days 1-5 and Days 8-9 depending on institutional preference.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DCLL9718S</intervention_name>
    <description>DCLL9718S will be administered as per the schedule specified in the respective arm.</description>
    <arm_group_label>Arm A: DCLL9718S</arm_group_label>
    <arm_group_label>Arm B: DCLL9718S and Azacitidine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azacitidine</intervention_name>
    <description>Azacitidine will be administered as per the schedule specified in the respective arm.</description>
    <arm_group_label>Arm B: DCLL9718S and Azacitidine</arm_group_label>
    <other_name>Vidaza</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of AML per World Health Organization (WHO) criteria (except acute&#xD;
             promyelocytic leukemia)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2&#xD;
&#xD;
          -  Adequate end-organ function&#xD;
&#xD;
          -  Willing and able to undergo a pre-treatment bone marrow aspirate and biopsy and&#xD;
             subsequent bone marrow aspirates and biopsies during treatment&#xD;
&#xD;
        Specifically for participants in Arm A:&#xD;
&#xD;
          -  Age greater than or equal to (&gt;/=) 18 years&#xD;
&#xD;
          -  Relapsed or refractory acute myeloid leukemia&#xD;
&#xD;
          -  Participants cannot have received more than two prior regimens&#xD;
&#xD;
        Specifically for participants in Arm B:&#xD;
&#xD;
          -  Treatment-naive participants with AML who are &gt;/=75 years old&#xD;
&#xD;
          -  Treatment-naive participants unfit for induction chemotherapy for AML due to&#xD;
             comorbidities who are &gt;/=65 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of acute promyelocytc leukemia&#xD;
&#xD;
          -  Prior allogeneic stem cell transplant or solid organ transplant&#xD;
&#xD;
          -  Active central nervous system (CNS) involvement by leukemia&#xD;
&#xD;
          -  History of idiopathic pulmonary fibrosis, organizing pneumonitis (for example [e.g.],&#xD;
             bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis&#xD;
&#xD;
          -  Treatment with investigational therapy within 14 days prior to Cycle 1, Day 1&#xD;
&#xD;
          -  Treatment with a monoclonal antibody within 30 days prior to Cycle 1, Day 1&#xD;
&#xD;
          -  Positive for hepatitis C virus (HCV) antibody at screening&#xD;
&#xD;
          -  Active hepatitis B virus (HBV) infection&#xD;
&#xD;
          -  Known positivity for human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  History of other malignancy within 2 years prior to screening&#xD;
&#xD;
          -  Family history of long QT syndrome, with a QTc interval greater than (&gt;) 480&#xD;
             millisecond (msec) at screening, or taking concurrent medications known to prolong&#xD;
             QT/QTc interval&#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>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital - Anschutz Cancer Pavilion</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1C9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Hospital; Department of Med Oncology</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jewish General Hospital / McGill University</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Korea, Republic of</country>
  </removed_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <last_update_submitted>November 18, 2019</last_update_submitted>
  <last_update_submitted_qc>November 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azacitidine</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/NCT03298516
org study id: GO39902
nct id: NCT03298516
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This Phase Ia/Ib, open-label, multicenter study will evaluate the safety, tolerability, and
      preliminary efficacy of DCLL9718S as a single agent (Phase Ia, Arm A) in participants with
      relapsed or refractory AML or in combination with azacitidine (Phase Ib, Arm B) in
      participants with previously untreated AML who are not eligible for intensive induction
      chemotherapy. Each arm will consist of two stages: a dose-escalation stage and an expansion
      stage. The dose-escalation stage is designed to establish the maximum tolerated dose (MTD)
      and recommended Phase II dose (RP2D) for DCLL9718S alone (Arm A) or in combination with
      azacitidine (Arm B). The dose-expansion stage is designed to characterize the long-term
      safety and tolerability of DCLL9718S.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of participants With Adverse Events (AEs)
time frame: Baseline up to end of study (up to approximately 3 years)
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
time frame: Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
measure: MTD of DCLL9718S
time frame: Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
measure: RP2D of DCLL9718S
time frame: Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
measure: Serum Concentration of DCLL9718S
time frame: up to 3 years
measure: Plasma Concentration of Azacitidine
time frame: up to 3 years
measure: Area Under the Concentration-Time Curve (AUC) of DCLL9718S
time frame: up to 3 years
measure: Maximum Plasma Concentration Observed (Cmax) of DCLL9718S
time frame: up to 3 years
measure: Total Clearance of DCLL9718S
time frame: up to 3 years
measure: Terminal Half-Life (t1/2) of DCLL9718S
time frame: up to 3 years
measure: Volume of Distribution Under Steady-State (Vss) of DCLL9718S
time frame: up to 3 years
measure: Percentage of Participants With Complete Remission (CR), CR With Incomplete Blood Count Recovery (CRi), CR With Incomplete Platelet Count Recovery (CRp), and Overall Response, Assessed as per International Working Group (IWG) Criteria
time frame: From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years)
measure: Duration of Response, Assessed as per IWG Criteria
time frame: From the date of first response to the earliest recurrence or disease progression (up to approximately 3 years)
measure: Overall Survival
time frame: From the date of first treatment to the date of death from any cause (up to approximately 3 years)
measure: Event-Free Survival (EFS), Assessed as per IWG Criteria
time frame: From the date of first treatment until treatment failure, relapsed from CR, CRp, or CRi, or death from any cause, whichever occurs first (up to approximately 3 years)
measure: Progression-Free Survival (PFS), Assessed as per IWG Criteria
time frame: From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years)
measure: Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S
time frame: Baseline up to end of study (up to approximately 3 years)
arm group label: Arm A: DCLL9718S
arm group type: Experimental
description: Participants will receive escalating doses of DCLL9718S intravenously (IV) in each 21-day cycle to determine MTD and RP2D in dose-escalation stage followed by DCLL9718S IV at RP2D in each 21-day cycle in dose-expansion stage until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
arm group label: Arm B: DCLL9718S and Azacitidine
arm group type: Experimental
description: Participants will receive escalating doses of DCLL9718S (starting dose: at least one dose level below a completed and tolerated DCLL9718S monotherapy in Arm A) IV in each 28-day cycle and azacitidine 75 milligrams per square meter (mg/m^2) subcutaneously (SC) or IV on Days 1-7 of each 28-day cycle to determine MTD and RP2D of DCLL9718S in dose-escalation stage followed by DCLL9718S IV at RP2D in each 28-day cycle and azacitidine 75 mg/m^2 SC or IV on Days 1-7 of each 28-day cycle in dose-expansion stage until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. Azacitidine may also be given on Days 1-5 and Days 8-9 depending on institutional preference.
intervention type: Drug
intervention name: DCLL9718S
description: DCLL9718S will be administered as per the schedule specified in the respective arm.
arm group label: Arm A: DCLL9718S
arm group label: Arm B: DCLL9718S and Azacitidine
intervention type: Drug
intervention name: Azacitidine
description: Azacitidine will be administered as per the schedule specified in the respective arm.
arm group label: Arm B: DCLL9718S and Azacitidine
other name: Vidaza
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Azacitidine