<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/NCT01690624</url>
  </required_header>
  <id_info>
    <org_study_id>1315.1</org_study_id>
    <nct_id>NCT01690624</nct_id>
  </id_info>
  <brief_title>BI 836858 Dose Escalation in Patients With Refractory or Relapsed Acute Myeloid Leukemia and in Patients in Complete Remission With High Risk to Relapse</brief_title>
  <official_title>A Phase I, Open-label, Cohort Dose Escalation Trial With BI 836858 in Patients With Refractory or Relapsed Acute Myeloid Leukemia and Patients With Acute Myeloid Leukemia in Complete Remission With High Risk to Relapse.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Patients with acute myeloid leukemia who experience a relapse after at least one prior&#xD;
      regimen may be enrolled in this trial. In addition, acute myeloid leukemia patients who are&#xD;
      in complete remission with high risk to relapse may be eligible for this trial. The trial&#xD;
      will examine whether monotherapy with BI 836858 is safe and tolerable at escalating dose&#xD;
      levels.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 13, 2012</start_date>
  <completion_date type="Actual">May 21, 2018</completion_date>
  <primary_completion_date type="Actual">May 21, 2018</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determination of the maximum tolerated dose of BI 836858</measure>
    <time_frame>up to 4 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with dose limiting toxicity during maximum tolerated dose evaluation for patients with refractory or relapsed acute myeloid leukemia</measure>
    <time_frame>up to 4 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with dose limiting toxicity during maximum tolerated dose evaluation for acute myeloid leukemia patients in complete remission with high risk to relapse</measure>
    <time_frame>up to 4 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum measured plasma concentration (Cmax)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to the maximum plasma concentration (tmax)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve over the time interval of one week (AUC0-168)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve over the time interval of one treatment cycle (AUC0-tz)</measure>
    <time_frame>up to 336 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC0-infinity)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t1/2)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time after intravenous infusion (MRT)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total plasma clearance (CL)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase (Vz)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution after intravenous infusion at steady state (Vss)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve over the time interval from zero to the time of the last quantifiable data point (AUC0-tz)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall response rate according to International Working Group (IWG) criteria (for refractory or relapsed acute myeloid leukemia patients only)</measure>
    <time_frame>up to 22 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival for patients with refractory or relapsed acute myeloid leukemia</measure>
    <time_frame>up to 22 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure for patients with refractory or relapsed acute myeloid leukemia</measure>
    <time_frame>up to 22 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure for acute myeloid leukemia patients in complete remission with high risk to relapse</measure>
    <time_frame>up to 22 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival for acute myeloid leukemia patients in complete remission with high risk to relapse</measure>
    <time_frame>up to 22 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Leukemia, Myeloid, Acute</condition>
  <arm_group>
    <arm_group_label>Patients with relapsed or refractoryAML</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with acute myeloid leukemia who have relapsed after 1 prior treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 836858</intervention_name>
    <description>Monotherapy with BI 836858 administered as intravenous infusion</description>
    <arm_group_label>Patients with relapsed or refractoryAML</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Diagnosis of relapsed or refractory AML with at least one prior treatment for acute&#xD;
             myeloid leukemia and patients with diagnosis of acute myeloid leukemia in complete&#xD;
             remission with high risk to relapse.&#xD;
&#xD;
          2. Expression of CD33 on more than 30% of bone marrow blasts at screening for patients&#xD;
             with refractory or relapsed acute myeloid leukemia is required. CD33 positive&#xD;
             expression of bone marrow blasts at the time of initial acute myeloid leukemia&#xD;
             diagnosis is sufficient for those patients in complete remission with high risk to&#xD;
             relapse.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group Performance Status 0, 1 or 2&#xD;
&#xD;
          4. Age 18 years or older&#xD;
&#xD;
          5. Written informed consent which is consistent with International Conference on&#xD;
             Harmonization, Good Clinical Practice (ICH-GCP) guidelines and local legislation.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Patients with acute promyelocytic leukemia according to WHO definition.&#xD;
&#xD;
          2. Patients with refractory or relapsed acute myeloid leukemia &gt; 5.000 blasts in the&#xD;
             peripheral blood.&#xD;
&#xD;
          3. Anti-leukemia therapy within two weeks before first treatment with BI 836858, 4 weeks&#xD;
             for biologics. Parallel treatment with Hydroxyurea ia allowed with refractory or&#xD;
             relapsed acute myeloid leukemia patients.&#xD;
&#xD;
          4. Allogeneic stem cell transplantation within the last 28 days before first treatment&#xD;
             with graft versus host disease requiring more than 20 mg of steroids per day. Steroid&#xD;
             dosage must be stable within two weeks prior to start of treatment.&#xD;
&#xD;
          5. Patients who are candidates for allogeneic stem cell transplantation (for patients&#xD;
             with refractory or relapsed acute myeloid leukemia).&#xD;
&#xD;
          6. Second malignancy currently requiring active therapy.&#xD;
&#xD;
          7. Symptomatic central nervous system involvement&#xD;
&#xD;
          8. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5&#xD;
             times the upper limit of normal (ULN), or AST or ALT greater than 5 times the ULN for&#xD;
             those with Gilbert syndrome.&#xD;
&#xD;
          9. Prothrombin time (PT) &gt;1.5 x ULN for subjects not on therapeutic vitamin K antagonists&#xD;
             (phenprocoumon, warfarin)&#xD;
&#xD;
         10. Bilirubin greater than 1.5 mg/dl (&gt;26 µmol/L) unless elevation is thought to be due to&#xD;
             hepatic infiltration by AML, Gilbert syndrome, or hemolysis.&#xD;
&#xD;
         11. Serum creatinine greater than 2.0 mg/dl&#xD;
&#xD;
         12. Known human immunodeficiency virus (HIV) infection or active hepatitis B virus or&#xD;
             hepatitis C virus infection.&#xD;
&#xD;
         13. Concomitant intercurrent illness, or any condition which in the opinion of the&#xD;
             Investigator, would compromise safe participation in the study, e.g. active severe&#xD;
             infection, unstable angina pectoris, new onset of exacerbation of a cardiac arrhythmia&#xD;
&#xD;
         14. Psychiatric illness or social situation that would limit compliance with trial&#xD;
             requirements&#xD;
&#xD;
         15. Concomitant therapy, which is considered relevant for the evaluation of the efficacy&#xD;
             or safety of the trial drug&#xD;
&#xD;
         16. Female patients of childbearing potential who are sexually active and unwilling to use&#xD;
             a medically acceptable method of contraception during the trial and for 6 months after&#xD;
             the last administration of BI 836858&#xD;
&#xD;
         17. Male patients with partners of childbearing potential who are unwilling to use condoms&#xD;
             in combination with a second effective method of contraception during the trial and&#xD;
             for 6 months after the last administration of BI 836858&#xD;
&#xD;
         18. Pregnant or nursing female patients&#xD;
&#xD;
         19. Treatment with another investigational agent under the following conditions:&#xD;
&#xD;
               1. Within two weeks (4 weeks for biologics or 5 half-lives, whichever is longer) of&#xD;
                  first administration of BI 836858; or&#xD;
&#xD;
               2. Patient has persistent toxicities from prior anti-leukemic therapies which are&#xD;
                  determined to be relevant by the Investigator.&#xD;
&#xD;
               3. Concomitant treatment with another investigational agent while participating in&#xD;
                  this trial.&#xD;
&#xD;
         20. Prior treatment with a CD33 antibody&#xD;
&#xD;
         21. Patient unable or unwilling to comply with the protocol.&#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>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint 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>The Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 24, 2012</study_first_posted>
  <last_update_submitted>May 22, 2018</last_update_submitted>
  <last_update_submitted_qc>May 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2018</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>
  <!-- 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/NCT01690624
org study id: 1315.1
nct id: NCT01690624
lead sponsor: 
Patients with acute myeloid leukemia who experience a relapse after at least one prior
      regimen may be enrolled in this trial. In addition, acute myeloid leukemia patients who are
      in complete remission with high risk to relapse may be eligible for this trial. The trial
      will examine whether monotherapy with BI 836858 is safe and tolerable at escalating dose
      levels.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determination of the maximum tolerated dose of BI 836858
time frame: up to 4 weeks
measure: Number of patients with dose limiting toxicity during maximum tolerated dose evaluation for patients with refractory or relapsed acute myeloid leukemia
time frame: up to 4 weeks
measure: Number of patients with dose limiting toxicity during maximum tolerated dose evaluation for acute myeloid leukemia patients in complete remission with high risk to relapse
time frame: up to 4 weeks
measure: Maximum measured plasma concentration (Cmax)
time frame: up to 168 hours
measure: Time from dosing to the maximum plasma concentration (tmax)
time frame: up to 168 hours
measure: Area under the plasma concentration-time curve over the time interval of one week (AUC0-168)
time frame: up to 168 hours
measure: Area under the plasma concentration-time curve over the time interval of one treatment cycle (AUC0-tz)
time frame: up to 336 hours
measure: Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC0-infinity)
time frame: up to 168 hours
measure: Terminal half-life (t1/2)
time frame: up to 168 hours
measure: Mean residence time after intravenous infusion (MRT)
time frame: up to 168 hours
measure: Total plasma clearance (CL)
time frame: up to 168 hours
measure: Apparent volume of distribution during the terminal phase (Vz)
time frame: up to 168 hours
measure: Volume of distribution after intravenous infusion at steady state (Vss)
time frame: up to 168 hours
measure: Area under the plasma concentration-time curve over the time interval from zero to the time of the last quantifiable data point (AUC0-tz)
time frame: up to 168 hours
measure: Best overall response rate according to International Working Group (IWG) criteria (for refractory or relapsed acute myeloid leukemia patients only)
time frame: up to 22 months
measure: Progression free survival for patients with refractory or relapsed acute myeloid leukemia
time frame: up to 22 months
measure: Time to treatment failure for patients with refractory or relapsed acute myeloid leukemia
time frame: up to 22 months
measure: Time to treatment failure for acute myeloid leukemia patients in complete remission with high risk to relapse
time frame: up to 22 months
measure: Progression free survival for acute myeloid leukemia patients in complete remission with high risk to relapse
time frame: up to 22 months
arm group label: Patients with relapsed or refractoryAML
arm group type: Experimental
description: Patients with acute myeloid leukemia who have relapsed after 1 prior treatment.
intervention type: Drug
intervention name: BI 836858
description: Monotherapy with BI 836858 administered as intravenous infusion
arm group label: Patients with relapsed or refractoryAML
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute