<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/NCT02238522</url>
  </required_header>
  <id_info>
    <org_study_id>ZEN-ONC3365-101</org_study_id>
    <nct_id>NCT02238522</nct_id>
  </id_info>
  <brief_title>Phase 1 Study Evaluating ZEN003365 in Relapsed/Refractory Lymphoproliferative Malignancies or Relapsed/Refractory AML</brief_title>
  <official_title>Phase 1 Open-label Dose Escalation and Expansion Study of ZEN003365 in Subjects With Relapsed or Refractory Lymphoproliferative Malignancies or Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zenith Epigenetics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zenith Epigenetics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine safety, tolerability, dose limiting toxicities&#xD;
      (DLT) and maximum tolerated dose (MTD) of ZEN003365 in patients with relapsed/refractory&#xD;
      lymphoproliferative malignancies (LPM) or relapsed/refractory acute myeloid leukemia (AML).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">January 2017</completion_date>
  <primary_completion_date type="Anticipated">June 2016</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose escalation stage - The safety of orally administered ZEN003365, assessed by frequency of adverse events, including worsening of medical conditions/diseases</measure>
    <time_frame>From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose escalation stage - To characterize the DLTs of orally administered ZEN003365, using NCI CTCAE v4.03</measure>
    <time_frame>The first 25 days of at least 12 doses of ZEN003365</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose expansion stage - Preliminary evidence of the antitumor activity of orally administered ZEN003365 in selected patients, assessed by objective response, duration of objective response and progression-free survival</measure>
    <time_frame>From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose expansion stage - The safety of orally administered ZEN003365, at the dose chosen based upon the dose escalation stage, assessed by frequency of adverse events, including worsening of medical conditions/diseases</measure>
    <time_frame>From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dose escalation stage - To characterize the pharmacokinetics (PK) of orally administered ZEN003365 in patients, using the following parameters: AUC, Tmax, Cmax, Cmin, pre-dose concentration, and accumulation ratio</measure>
    <time_frame>From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose expansion stage - To characterize the PK of orally administered ZEN003365, at the dose chosen based upon the dose escalation stage, using the following parameters: AUC, Tmax, Cmax, Cmin, pre-dose concentration, and accumulation ratio</measure>
    <time_frame>From Screening Visit through 40 days after the last day of treatment with ZEN003365 (19 weeks, average)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Lymphoproliferative Malignancies</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Dose Escalation Stage - ZEN003365</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion Stage - ZEN003365</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ZEN003365</intervention_name>
    <arm_group_label>Dose Escalation Stage - ZEN003365</arm_group_label>
    <arm_group_label>Dose Expansion Stage - ZEN003365</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Dose Escalation and Expansion Stages:&#xD;
&#xD;
          -  ECOG performance status ≤ 1 for LPM patients, ≤ 2 for AML patients&#xD;
&#xD;
          -  Age 18 years or older&#xD;
&#xD;
          -  Adverse events (AEs), except for alopecia, from any previous treatments must have&#xD;
             recovered to eligibility levels from prior toxicity&#xD;
&#xD;
          -  Adequate renal, hepatic and coagulation function, as specified per protocol&#xD;
&#xD;
          -  Written informed consent granted prior to any study-specific screening procedures&#xD;
&#xD;
        LPM Patients:&#xD;
&#xD;
          -  Histologically confirmed lymphoproliferative malignancy&#xD;
&#xD;
          -  Have received prior protocol-specified disease-dependent prior treatments&#xD;
&#xD;
          -  Have measurable disease&#xD;
&#xD;
          -  Platelets ≥ 75,000/µL (≥50,000/µL if bone marrow involvement), absolute neutrophil&#xD;
             count (ANC) ≥ 1,000/ µL, and hemoglobin (Hgb) ≥ 8 g/dL&#xD;
&#xD;
          -  Patients must have been off previous anticancer therapy for at least 3 weeks or 5&#xD;
             half-lives, whichever is longer, and the subject must have recovered to eligibility&#xD;
             levels from prior toxicity&#xD;
&#xD;
        AML:&#xD;
&#xD;
          -  Refractory or relapsed AML patients, without curative intent, e.g., not a stem cell&#xD;
             transplant candidate&#xD;
&#xD;
          -  Any prior chemotherapy must have been completed ≥ 2 weeks, any therapy with biologics&#xD;
             must have been completed ≥ 4 weeks prior to day 1 of study treatment, and the&#xD;
             participant must have recovered to eligibility levels from prior toxicity&#xD;
&#xD;
          -  Blast count ≤ 10,000/µL prior to initiation of therapy&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Dose Escalation and Expansion Stages:&#xD;
&#xD;
          -  Prior exposure to a BET inhibitor&#xD;
&#xD;
          -  Prior allogeneic hematopoietic cell transplant&#xD;
&#xD;
          -  Chronic graft versus host disease&#xD;
&#xD;
          -  Known, active fungal, bacterial, and/or viral infection&#xD;
&#xD;
          -  Uncontrolled autoimmune hemolytic anemia or thrombocytopenia&#xD;
&#xD;
          -  Current subdural hematoma&#xD;
&#xD;
          -  CNS or leptomeningeal metastases&#xD;
&#xD;
          -  Requirement for medications or agents known to be sensitive CYP3A4 substrate drugs,&#xD;
             CYP3A4 substrate drugs with a narrow therapeutic range or to be strong&#xD;
             inhibitors/inducers of CYP3A4&#xD;
&#xD;
          -  Requirement for immunosuppressive agents&#xD;
&#xD;
          -  Evidence of significant cardiovascular disease or significant screening ECG&#xD;
             abnormalities&#xD;
&#xD;
          -  Any medical conditions that, in the Investigator's opinion, would impose excessive&#xD;
             risk to the patient.&#xD;
&#xD;
        AML patients:&#xD;
&#xD;
          -  Acute promyelocytic leukemia (APL)&#xD;
&#xD;
          -  Chronic myeloid leukemia (CML) in blast crisis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>St. Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Willamette Valley Cancer Institute and Research Center</name>
      <address>
        <city>Springfield</city>
        <state>Oregon</state>
        <zip>97477</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2014</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>November 12, 2014</last_update_submitted>
  <last_update_submitted_qc>November 12, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 13, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic lymphocytic leukemia</keyword>
  <keyword>B-prolymphocytic leukemia</keyword>
  <keyword>Non-Hodgkin's lymphoma</keyword>
  <keyword>follicular lymphoma</keyword>
  <keyword>mantle cell lymphoma</keyword>
  <keyword>marginal zone lymphoma</keyword>
  <keyword>small lymphocytic lymphoma</keyword>
  <keyword>diffuse large B-cell lymphoma</keyword>
  <keyword>unclassifiable lymphoma</keyword>
  <keyword>T-cell lymphoma</keyword>
  <keyword>Richter's syndrome</keyword>
  <keyword>Waldenström's macroglobulinemia</keyword>
  <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>
    <mesh_term>Neoplasms</mesh_term>
  </condition_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/NCT02238522
org study id: ZEN-ONC3365-101
nct id: NCT02238522
lead sponsor: 
has dmc: No
The purpose of this study is to determine safety, tolerability, dose limiting toxicities
      (DLT) and maximum tolerated dose (MTD) of ZEN003365 in patients with relapsed/refractory
      lymphoproliferative malignancies (LPM) or relapsed/refractory acute myeloid leukemia (AML).
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose escalation stage - The safety of orally administered ZEN003365, assessed by frequency of adverse events, including worsening of medical conditions/diseases
time frame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
measure: Dose escalation stage - To characterize the DLTs of orally administered ZEN003365, using NCI CTCAE v4.03
time frame: The first 25 days of at least 12 doses of ZEN003365
measure: Dose expansion stage - Preliminary evidence of the antitumor activity of orally administered ZEN003365 in selected patients, assessed by objective response, duration of objective response and progression-free survival
time frame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
measure: Dose expansion stage - The safety of orally administered ZEN003365, at the dose chosen based upon the dose escalation stage, assessed by frequency of adverse events, including worsening of medical conditions/diseases
time frame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
measure: Dose escalation stage - To characterize the pharmacokinetics (PK) of orally administered ZEN003365 in patients, using the following parameters: AUC, Tmax, Cmax, Cmin, pre-dose concentration, and accumulation ratio
time frame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
measure: Dose expansion stage - To characterize the PK of orally administered ZEN003365, at the dose chosen based upon the dose escalation stage, using the following parameters: AUC, Tmax, Cmax, Cmin, pre-dose concentration, and accumulation ratio
time frame: From Screening Visit through 40 days after the last day of treatment with ZEN003365 (19 weeks, average)
arm group label: Dose Escalation Stage - ZEN003365
arm group type: Experimental
description: ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients
arm group label: Dose Expansion Stage - ZEN003365
arm group type: Experimental
description: ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients
intervention type: Drug
intervention name: ZEN003365
arm group label: Dose Escalation Stage - ZEN003365
arm group label: Dose Expansion Stage - ZEN003365
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Neoplasms