<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/NCT01664897</url>
  </required_header>
  <id_info>
    <org_study_id>2012-0060</org_study_id>
    <secondary_id>NCI-2012-02073</secondary_id>
    <secondary_id>2012-0060</secondary_id>
    <secondary_id>P30CA016672</secondary_id>
    <nct_id>NCT01664897</nct_id>
  </id_info>
  <brief_title>Erlotinib Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia</brief_title>
  <official_title>A Pilot Phase II Study of Erlotinib for the Treatment of Patients With Refractory/Relapsed AML</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Astellas Pharma Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot phase II trial studies how well erlotinib hydrochloride works in treating patients&#xD;
      with relapsed or refractory acute myeloid leukemia. Erlotinib hydrochloride may stop the&#xD;
      growth of cancer cells by blocking some of the enzymes needed for cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the efficacy of erlotinib (erlotinib hydrochloride) in patients with refractory&#xD;
      or relapsed acute myeloid leukemia (AML).&#xD;
&#xD;
      II. To determine the safety and tolerability of erlotinib in this patient population.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To investigate inhibitory effect of this drug on spleen tyrosine kinase (SYK) and its&#xD;
      down-stream targets such as mitogen-activated protein kinase 8 (JNK), mitogen-activated&#xD;
      protein kinase (MAPK) and mitogen-activated protein kinase 1 (Erk).&#xD;
&#xD;
      II. To evaluate its role in janus kinase (Jak)/signal transducer and activator of&#xD;
      transcription (STAT) pathway and to investigate erlotinib-mediated cell death and/or&#xD;
      differentiation.&#xD;
&#xD;
      III. To quantitate concentrations of plasma erlotinib.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses&#xD;
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 16, 2013</start_date>
  <completion_date type="Actual">October 25, 2018</completion_date>
  <primary_completion_date type="Actual">October 25, 2018</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>Participants With a Response</measure>
    <time_frame>Up to 3 months post-treatment</time_frame>
    <description>Overall Response is complete remission (CR) + CR with incomplete hematologic recovery (CRi) + Partial remission (PR) + Hematologic improvement (HI) + Morphologic Leukemia-Free State (MLF). (CR) is Bone marrow; &lt;/=5% blasts, no Auer rods or extramedullary disease and peripheral blood counts &gt;/= 1.0x10^9/L Neutrophils, &gt;/= 100x10^9/L platelets and no circulating blasts. (CRi), same as CR for bone marrow and &lt;1.0x10^9/L neutrophils and &lt; 100x10^9/L platelets in peripheral blood counts. PR is all CR criteria if abnormal prior to treatment except &gt;/= 50%reduction in bone marrow blast but still &gt; 5%. MLF is &lt;/=5% myeloblasts on bone marrow . HI response must be described by the number of positively affected cell lines..</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Clinically Significant, Non-hematologic Grade 3 or 4 Toxicities at Least Possibly Related to Erlotinib Hydrochloride</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Safety summaries will include tabulations in the form of tables and listings. The number of participants affected by treatment-emergent adverse events will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 97 weeks</time_frame>
    <description>Time from date of treatment start until date of death due to any cause or last Follow-up.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Event-free Survival</measure>
    <time_frame>Up to 21 weeks</time_frame>
    <description>Time from date of treatment start until the date of first objective documentation of disease-relapse.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biomarker Expressions</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Descriptive statistics will be used to summarize the expression of biomarkers and the concentrations of plasma erlotinib hydrochloride. The Wilcoxon rank sum test will be used to compare the expressions of biomarkers and concentrations of plasma erlotinib hydrochloride between patients with and without response.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome</condition>
  <condition>Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11</condition>
  <condition>Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11</condition>
  <condition>Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1</condition>
  <condition>Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A</condition>
  <condition>Adult Acute Promyelocytic Leukemia With PML-RARA</condition>
  <condition>Alkylating Agent-Related Acute Myeloid Leukemia</condition>
  <condition>Chronic Myelomonocytic Leukemia</condition>
  <condition>Myelodysplastic Syndrome</condition>
  <condition>Previously Treated Myelodysplastic Syndrome</condition>
  <condition>Recurrent Adult Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Treatment (erlotinib hydrochloride)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Erlotinib Hydrochloride</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (erlotinib hydrochloride)</arm_group_label>
    <other_name>Cp-358,774</other_name>
    <other_name>OSI-774</other_name>
    <other_name>Tarceva</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (erlotinib hydrochloride)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with AML who have either been refractory to prior therapy or have relapsed&#xD;
             after prior therapy; patients with myelodysplastic syndromes (MDS) or chronic&#xD;
             myelomonocytic leukemia (CMML) who received therapy with a hypomethylating agent and&#xD;
             progress to AML are eligible if they have received any therapy for MDS and failed&#xD;
             (i.e., lack or loss of response) regardless of whether they have received therapy for&#xD;
             AML or not; the World Health Organization (WHO) classification will be used for AML&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2&#xD;
&#xD;
          -  Total bilirubin =&lt; 2 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) =&lt; 2.5 x ULN&#xD;
&#xD;
          -  Creatinine =&lt; 2 x ULN&#xD;
&#xD;
          -  Patients must provide written informed consent&#xD;
&#xD;
          -  Patients must have been off chemotherapy for 2 weeks prior to entering this study,&#xD;
             unless there is evidence of rapidly progressive disease, and must have recovered from&#xD;
             the clinically significant toxic effects of that therapy to at least grade 1; use of&#xD;
             hydroxyurea for patients with rapidly proliferative disease is allowed before the&#xD;
             start of study therapy and for the first four weeks on therapy&#xD;
&#xD;
          -  Patients-both males and females-with reproductive potential (i.e., menopausal for less&#xD;
             than 1 year and not surgically sterilized) must practice effective contraceptive&#xD;
             measures throughout the study; women of childbearing potential must provide a negative&#xD;
             pregnancy test (serum or urine) within 14 days prior to initiation of study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with known allergy or hypersensitivity to erlotinib&#xD;
&#xD;
          -  Patients with any other known disease (except carcinoma in-situ) concurrent severe&#xD;
             and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular&#xD;
             disease including congestive heart failure New York Heart Association [NYHA] class III&#xD;
             or IV, myocardial infarction within 6 months, and poorly controlled hypertension;&#xD;
             chronic renal failure; or active uncontrolled infection) which, in the opinion of the&#xD;
             investigator could compromise participation in the study&#xD;
&#xD;
          -  Patients unwilling or unable to comply with the protocol&#xD;
&#xD;
          -  Significant gastrointestinal disorders that may interfere with absorption of erlotinib&#xD;
&#xD;
          -  Patients who can receive a stem cell transplant within 4 weeks&#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>Jorge Cortes</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>August 10, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 14, 2012</study_first_posted>
  <results_first_submitted>November 6, 2019</results_first_submitted>
  <results_first_submitted_qc>December 18, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">January 7, 2020</results_first_posted>
  <last_update_submitted>December 18, 2019</last_update_submitted>
  <last_update_submitted_qc>December 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 7, 2020</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>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Chronic</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Juvenile</mesh_term>
    <mesh_term>Leukemia, Promyelocytic, Acute</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Erlotinib Hydrochloride</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 19, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT01664897/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment Period: May 2013 to May 2014</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Erlotinib Hydrochloride)</title>
          <description>Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Erlotinib Hydrochloride: Given PO&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Erlotinib Hydrochloride)</title>
          <description>Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Erlotinib Hydrochloride: Given PO&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="29"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="67" lower_limit="20" upper_limit="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Participants With a Response</title>
        <description>Overall Response is complete remission (CR) + CR with incomplete hematologic recovery (CRi) + Partial remission (PR) + Hematologic improvement (HI) + Morphologic Leukemia-Free State (MLF). (CR) is Bone marrow; &lt;/=5% blasts, no Auer rods or extramedullary disease and peripheral blood counts &gt;/= 1.0x10^9/L Neutrophils, &gt;/= 100x10^9/L platelets and no circulating blasts. (CRi), same as CR for bone marrow and &lt;1.0x10^9/L neutrophils and &lt; 100x10^9/L platelets in peripheral blood counts. PR is all CR criteria if abnormal prior to treatment except &gt;/= 50%reduction in bone marrow blast but still &gt; 5%. MLF is &lt;/=5% myeloblasts on bone marrow . HI response must be described by the number of positively affected cell lines..</description>
        <time_frame>Up to 3 months post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Erlotinib Hydrochloride)</title>
            <description>Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Erlotinib Hydrochloride: Given PO&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With a Response</title>
          <description>Overall Response is complete remission (CR) + CR with incomplete hematologic recovery (CRi) + Partial remission (PR) + Hematologic improvement (HI) + Morphologic Leukemia-Free State (MLF). (CR) is Bone marrow; &lt;/=5% blasts, no Auer rods or extramedullary disease and peripheral blood counts &gt;/= 1.0x10^9/L Neutrophils, &gt;/= 100x10^9/L platelets and no circulating blasts. (CRi), same as CR for bone marrow and &lt;1.0x10^9/L neutrophils and &lt; 100x10^9/L platelets in peripheral blood counts. PR is all CR criteria if abnormal prior to treatment except &gt;/= 50%reduction in bone marrow blast but still &gt; 5%. MLF is &lt;/=5% myeloblasts on bone marrow . HI response must be described by the number of positively affected cell lines..</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Incidence of Clinically Significant, Non-hematologic Grade 3 or 4 Toxicities at Least Possibly Related to Erlotinib Hydrochloride</title>
        <description>Safety summaries will include tabulations in the form of tables and listings. The number of participants affected by treatment-emergent adverse events will be reported.</description>
        <time_frame>Up to 30 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Erlotinib Hydrochloride)</title>
            <description>Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Erlotinib Hydrochloride: Given PO&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Clinically Significant, Non-hematologic Grade 3 or 4 Toxicities at Least Possibly Related to Erlotinib Hydrochloride</title>
          <description>Safety summaries will include tabulations in the form of tables and listings. The number of participants affected by treatment-emergent adverse events will be reported.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival</title>
        <description>Time from date of treatment start until date of death due to any cause or last Follow-up.</description>
        <time_frame>Up to 97 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Erlotinib Hydrochloride)</title>
            <description>Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Erlotinib Hydrochloride: Given PO&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Time from date of treatment start until date of death due to any cause or last Follow-up.</description>
          <units>Weeks</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14" lower_limit="2.3" upper_limit="96.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Event-free Survival</title>
        <description>Time from date of treatment start until the date of first objective documentation of disease-relapse.</description>
        <time_frame>Up to 21 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Erlotinib Hydrochloride)</title>
            <description>Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Erlotinib Hydrochloride: Given PO&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Event-free Survival</title>
          <description>Time from date of treatment start until the date of first objective documentation of disease-relapse.</description>
          <units>Weeks</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="1.7" upper_limit="21.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biomarker Expressions</title>
        <description>Descriptive statistics will be used to summarize the expression of biomarkers and the concentrations of plasma erlotinib hydrochloride. The Wilcoxon rank sum test will be used to compare the expressions of biomarkers and concentrations of plasma erlotinib hydrochloride between patients with and without response.</description>
        <time_frame>Up to 30 days</time_frame>
        <population>Samples and data required for the above outcome measure were not done, therefore we cannot report any outcomes for the above outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Erlotinib Hydrochloride)</title>
            <description>Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Erlotinib Hydrochloride: Given PO&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Biomarker Expressions</title>
          <description>Descriptive statistics will be used to summarize the expression of biomarkers and the concentrations of plasma erlotinib hydrochloride. The Wilcoxon rank sum test will be used to compare the expressions of biomarkers and concentrations of plasma erlotinib hydrochloride between patients with and without response.</description>
          <population>Samples and data required for the above outcome measure were not done, therefore we cannot report any outcomes for the above outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Erlotinib Hydrochloride)</title>
          <description>Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Erlotinib Hydrochloride: Given PO&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood and Lymphatic System disorder - other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Espohageal Ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Oral Mucositis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Neutropenic Fever</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Tumor Lysis Syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleuritic Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Thromboembolic Event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Watery eyes</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Edema</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Neutropenic Fever</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle Aches</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Shortness of breath</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jorge Cortes MD./Professor</name_or_title>
      <organization>The University of Texas MD Anderson Cancer Center</organization>
      <phone>713-794-5783</phone>
      <email>jcortes@mdanderson.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01664897
org study id: 2012-0060
secondary id: NCI-2012-02073
secondary id: 2012-0060
secondary id: P30CA016672
nct id: NCT01664897
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This pilot phase II trial studies how well erlotinib hydrochloride works in treating patients
      with relapsed or refractory acute myeloid leukemia. Erlotinib hydrochloride may stop the
      growth of cancer cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:

      I. To assess the efficacy of erlotinib (erlotinib hydrochloride) in patients with refractory
      or relapsed acute myeloid leukemia (AML).

      II. To determine the safety and tolerability of erlotinib in this patient population.

      SECONDARY OBJECTIVES:

      I. To investigate inhibitory effect of this drug on spleen tyrosine kinase (SYK) and its
      down-stream targets such as mitogen-activated protein kinase 8 (JNK), mitogen-activated
      protein kinase (MAPK) and mitogen-activated protein kinase 1 (Erk).

      II. To evaluate its role in janus kinase (Jak)/signal transducer and activator of
      transcription (STAT) pathway and to investigate erlotinib-mediated cell death and/or
      differentiation.

      III. To quantitate concentrations of plasma erlotinib.

      OUTLINE:

      Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Participants With a Response
time frame: Up to 3 months post-treatment
description: Overall Response is complete remission (CR) + CR with incomplete hematologic recovery (CRi) + Partial remission (PR) + Hematologic improvement (HI) + Morphologic Leukemia-Free State (MLF). (CR) is Bone marrow; </=5% blasts, no Auer rods or extramedullary disease and peripheral blood counts >/= 1.0x10^9/L Neutrophils, >/= 100x10^9/L platelets and no circulating blasts. (CRi), same as CR for bone marrow and <1.0x10^9/L neutrophils and < 100x10^9/L platelets in peripheral blood counts. PR is all CR criteria if abnormal prior to treatment except >/= 50%reduction in bone marrow blast but still > 5%. MLF is </=5% myeloblasts on bone marrow . HI response must be described by the number of positively affected cell lines..
measure: Incidence of Clinically Significant, Non-hematologic Grade 3 or 4 Toxicities at Least Possibly Related to Erlotinib Hydrochloride
time frame: Up to 30 days
description: Safety summaries will include tabulations in the form of tables and listings. The number of participants affected by treatment-emergent adverse events will be reported.
measure: Overall Survival
time frame: Up to 97 weeks
description: Time from date of treatment start until date of death due to any cause or last Follow-up.
measure: Event-free Survival
time frame: Up to 21 weeks
description: Time from date of treatment start until the date of first objective documentation of disease-relapse.
measure: Biomarker Expressions
time frame: Up to 30 days
description: Descriptive statistics will be used to summarize the expression of biomarkers and the concentrations of plasma erlotinib hydrochloride. The Wilcoxon rank sum test will be used to compare the expressions of biomarkers and concentrations of plasma erlotinib hydrochloride between patients with and without response.
arm group label: Treatment (erlotinib hydrochloride)
arm group type: Experimental
description: Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Erlotinib Hydrochloride
description: Given PO
arm group label: Treatment (erlotinib hydrochloride)
other name: Cp-358,774
other name: OSI-774
other name: Tarceva
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (erlotinib hydrochloride)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jorge Cortes
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Leukemia, Myelomonocytic, Chronic
mesh term: Leukemia, Myelomonocytic, Juvenile
mesh term: Leukemia, Promyelocytic, Acute
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
mesh term: Erlotinib Hydrochloride
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 