<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/NCT02996474</url>
  </required_header>
  <id_info>
    <org_study_id>170026</org_study_id>
    <secondary_id>17-H-0026</secondary_id>
    <nct_id>NCT02996474</nct_id>
  </id_info>
  <brief_title>Pembrolizumab and Decitabine for Refractory or Relapsed Acute Myeloid Leukemia</brief_title>
  <official_title>Pembrolizumab and Decitabine for Refractory or Relapsed Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</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>
      Background:&#xD;
&#xD;
      Acute myeloid leukemia (AML) is a cancer of the white blood cells. It is fatal if not&#xD;
      treated. Treatment for AML that has not responded to treatment (refractory) or has returned&#xD;
      after treatment (relapsed) often do not work. Researchers want to see if an immunotherapy&#xD;
      drug, combined with a less intense chemotherapy, may be able to help.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To test if pembrolizumab, in combination with decitabine, is a possible treatment for people&#xD;
      with relapsed or refractory AML.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Adults 18 years of age and older with refractory AML or relapsed AML.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be first screened for eligibility.&#xD;
&#xD;
      The study is counted in 21-day cycles. The initial phase of the study consists of 8 cycles.&#xD;
      Participants may be in the study for up to 2 years if they are responding to the treatment.&#xD;
&#xD;
      The first 3 weeks of treatment is usually done in the hospital. The rest may be done as an&#xD;
      outpatient.&#xD;
&#xD;
      Participants will get pembrolizumab at the beginning of each cycle through an IV.&#xD;
&#xD;
      Participants will usually get decitabine by IV on days 8 12 and days 15 19 of every other&#xD;
      cycle.&#xD;
&#xD;
      Participants will give blood samples.&#xD;
&#xD;
      Participants will have bone marrow exams. A needle will be inserted into the hip to extract&#xD;
      cells from the bone marrow.&#xD;
&#xD;
      Some participants may give a sample of saliva from the inside of their cheek.&#xD;
&#xD;
      Some participants may give a small skin sample. The top layer of the skin is removed.&#xD;
&#xD;
      Some patients may require leukapheresis before starting treatment. This is a procedure to&#xD;
      remove leukemia cells in the blood stream.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pilot study to determine the feasibility of a novel combination of Pembrolizumab&#xD;
      and Decitabine in relapsed/refractory adult AML patients. While both Pembrolizumab and&#xD;
      Decitabine are FDA approved agents, this study will explore giving these drugs in combination&#xD;
      for this population of patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 16, 2016</start_date>
  <completion_date type="Actual">April 2, 2019</completion_date>
  <primary_completion_date type="Actual">April 2, 2019</primary_completion_date>
  <phase>Phase 1/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>Feasibility of a Novel Combination of Pembrolizumab and Decitabine in Relapsed/Refractory Acute Myeloid Leukemia Participants</measure>
    <time_frame>24 weeks</time_frame>
    <description>The number of patients who could be treated with a novel combination of Pembrolizumab and Decitabine in relapsed/refractory Acute Myeloid Leukemia participants without being removed from the protocol due to treatment related toxicities.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Days to First Response From Start of Study to Initial Achievement of First Response (mCR, mCRi, CR, CRi, PR, or SD)</measure>
    <time_frame>At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)</time_frame>
    <description>Time to first response (days) is time from start of study to first response (mCR, mCRi, CR, CRi, PR, or SD) in relapsed/refractory acute myeloid leukemia (AML) participants.&#xD;
Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Days to Best Response From Start of Study to Initial Achievement of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)</measure>
    <time_frame>At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)</time_frame>
    <description>Time to Best Response is defined as time (days) from start of study to initial achievement of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Duration (Days) of Response From Initial Achievement of Response to Loss of Response (mCR, mCRi, CR, CRi, PR, or SD)</measure>
    <time_frame>At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)</time_frame>
    <description>To determine duration (days) of response as defined as time from initial achievement of response to loss of response (mCR, mCRi, CR, CRi, PR, or SD).&#xD;
Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Duration (Days) of Best Response From Initial Achievement of Best Response to Loss of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)</measure>
    <time_frame>At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)</time_frame>
    <description>Duration of Best Response is time (days) from initial achievement of best response to loss of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>from enrollment until date of death, assessed up to 24 weeks</time_frame>
    <description>Number of participants overall survival is defined as death from any cause</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Relapsed Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory AML.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>200 mg will be administered as a 30 minute IV infusion every 3 weeks. Every effort should be made to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min).</description>
    <arm_group_label>Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia</arm_group_label>
    <other_name>Keytruda</other_name>
    <other_name>MK-3475</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Decitabine</intervention_name>
    <description>Will be administered at a dose of 20 mg/m^2 by continuous intravenous infusion over 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7). Decitabine should be repeated every 6 weeks.</description>
    <arm_group_label>Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia</arm_group_label>
    <other_name>Dacogen</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Unequivocal diagnosis of relapsed or refractory acute myeloid leukemia (AML) confirmed&#xD;
             by an NIH attending pathologist within 30 days of study enrollment (includes residual&#xD;
             AML as confirmed by institutional standards by NIH pathologists&#xD;
&#xD;
          -  Received at least one prior AML therapy before study enrollment.&#xD;
&#xD;
          -  Ability to comprehend the investigational nature of the study and provide informed&#xD;
             consent.&#xD;
&#xD;
          -  Be at least 18 years of age on day of signing informed consent.&#xD;
&#xD;
          -  Availability of a physician willing to assume clinical care after completion of the&#xD;
             study.&#xD;
&#xD;
          -  Be willing to provide blood and bone marrow for research as described in the study.&#xD;
&#xD;
          -  Have a performance status of less than or equal to 1 on the ECOG Performance Scale&#xD;
&#xD;
          -  Demonstrate adequate organ function as defined below, all screening labs should be&#xD;
             performed within 14 days of treatment initiation.&#xD;
&#xD;
          -  Female subject of childbearing potential should have a negative urine or serum&#xD;
             pregnancy within 72 hours prior to receiving the first dose of study medication. If&#xD;
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test&#xD;
             will be required.&#xD;
&#xD;
          -  Female subjects of childbearing potential must be willing to use an adequate method of&#xD;
             contraception; Contraception, for the course of the study through 120 days after the&#xD;
             last dose of study medication. Note: Abstinence is acceptable if this is the usual&#xD;
             lifestyle and preferred contraception for the subject.&#xD;
&#xD;
          -  Male subjects of childbearing potential must agree to use an adequate method of&#xD;
             contraception starting with the first dose of study therapy through 120 days after the&#xD;
             last dose of study therapy. Note: Abstinence is acceptable if this is the usual&#xD;
             lifestyle and preferred contraception for the subject.&#xD;
&#xD;
          -  Adequate Organ Function Laboratory Values: System Laboratory - Value&#xD;
&#xD;
               -  Renal&#xD;
&#xD;
                  ---Serum Creatinine - Less than or equal to 1.5 X upper limit of normal (ULN)&#xD;
&#xD;
               -  Hepatic&#xD;
&#xD;
                    -  Serum total bilirubin Less than or equal to 1.5 X ULN OR&#xD;
&#xD;
                    -  Direct bilirubin less than or equal to ULN for subjects with total bilirubin&#xD;
                       levels greater than 1.5 ULN&#xD;
&#xD;
                    -  AST (SGOT) and ALT(SGPT) Less than or equal to 3 X ULN&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        The subject must be excluded from participating in the trial if the subject:&#xD;
&#xD;
          -  Has a diagnosis of acute promyelocytic leukemia (APL)&#xD;
&#xD;
          -  Has previously received an allogeneic hematopoietic stem cell transplant.&#xD;
&#xD;
          -  Has received AML treatment with an investigational therapy or device within 4 weeks of&#xD;
             the first dose of treatment.&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any&#xD;
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial&#xD;
             treatment.&#xD;
&#xD;
          -  Has a known history of active TB (Bacillus Tuberculosis)&#xD;
&#xD;
          -  Has hypersensitivity to pembrolizumab or any of its excipients.&#xD;
&#xD;
          -  Has hypersensitivity to decitabine or any of its excipients.&#xD;
&#xD;
          -  Has received more than two prior cycles of decitabine.&#xD;
&#xD;
          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study&#xD;
             Day 1.&#xD;
&#xD;
          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy&#xD;
             within 2 weeks prior to study Day 1.&#xD;
&#xD;
             --Note: Subjects who have received cytoreductive therapy with hydroxyurea at any time&#xD;
             prior to study Day 1 are an exception to this criterion.&#xD;
&#xD;
          -  Has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse&#xD;
             events due to previously administered AML therapy agents.&#xD;
&#xD;
               -  Note: Subjects with less than or equal to Grade 2 neuropathy are an exception and&#xD;
                  may qualify for the study.&#xD;
&#xD;
               -  Note: If subject received major surgery, they must have recovered adequately from&#xD;
                  the toxicity and/or complications from the intervention prior to starting&#xD;
                  therapy.&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment.&#xD;
             Patients with basal cell carcinoma of the skin or squamous cell carcinoma of the skin&#xD;
             that has undergone potentially curative therapy or in situ cervical cancer would not&#xD;
             be excluded.&#xD;
&#xD;
          -  Has known malignant central nervous system (CNS) involvement.&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment.&#xD;
&#xD;
          -  Has history of (non-infectious) pneumonitis that required steroids, evidence of&#xD;
             interstitial lung disease or active, non-infectious pneumonitis.&#xD;
&#xD;
          -  Has an active infection requiring intravenous systemic therapy.&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject s&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment.&#xD;
&#xD;
          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.&#xD;
&#xD;
          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA&#xD;
             [qualitative] is detected).&#xD;
&#xD;
          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:&#xD;
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and&#xD;
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist ) are live&#xD;
             attenuated vaccines, and are not allowed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher S Hourigan, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Heart, Lung, and Blood Institute (NHLBI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-H-0026.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Goswami M, Gui G, Dillon LW, Lindblad KE, Thompson J, Valdez J, Kim DY, Ghannam JY, Oetjen KA, Destefano CB, Smith DM, Tekleab H, Li Y, Dagur P, Hughes T, Marte JL, Del Rivero J, Klubo-Gwiezdzinksa J, Gulley JL, Calvo KR, Lai C, Hourigan CS. Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia. J Immunother Cancer. 2022 Jan;10(1):e003392. doi: 10.1136/jitc-2021-003392.</citation>
    <PMID>35017151</PMID>
  </reference>
  <verification_date>November 20, 2019</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 19, 2016</study_first_posted>
  <results_first_submitted>May 4, 2020</results_first_submitted>
  <results_first_submitted_qc>May 4, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">May 21, 2020</results_first_posted>
  <last_update_submitted>December 1, 2022</last_update_submitted>
  <last_update_submitted_qc>December 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pembrolizumab</keyword>
  <keyword>Decitabine</keyword>
  <keyword>AML (Acute Myelogenous Leukemia)</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Decitabine</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 27, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT02996474/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia</title>
          <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia</title>
          <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="1"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </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="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Feasibility of a Novel Combination of Pembrolizumab and Decitabine in Relapsed/Refractory Acute Myeloid Leukemia Participants</title>
        <description>The number of patients who could be treated with a novel combination of Pembrolizumab and Decitabine in relapsed/refractory Acute Myeloid Leukemia participants without being removed from the protocol due to treatment related toxicities.</description>
        <time_frame>24 weeks</time_frame>
        <population>All patients enrolled on study.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia</title>
            <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility of a Novel Combination of Pembrolizumab and Decitabine in Relapsed/Refractory Acute Myeloid Leukemia Participants</title>
          <description>The number of patients who could be treated with a novel combination of Pembrolizumab and Decitabine in relapsed/refractory Acute Myeloid Leukemia participants without being removed from the protocol due to treatment related toxicities.</description>
          <population>All patients enrolled on study.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Days to First Response From Start of Study to Initial Achievement of First Response (mCR, mCRi, CR, CRi, PR, or SD)</title>
        <description>Time to first response (days) is time from start of study to first response (mCR, mCRi, CR, CRi, PR, or SD) in relapsed/refractory acute myeloid leukemia (AML) participants.&#xD;
Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
        <time_frame>At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)</time_frame>
        <population>Includes all participants that received treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia</title>
            <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).</description>
          </group>
        </group_list>
        <measure>
          <title>Median Days to First Response From Start of Study to Initial Achievement of First Response (mCR, mCRi, CR, CRi, PR, or SD)</title>
          <description>Time to first response (days) is time from start of study to first response (mCR, mCRi, CR, CRi, PR, or SD) in relapsed/refractory acute myeloid leukemia (AML) participants.&#xD;
Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
          <population>Includes all participants that received treatment.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42" lower_limit="37" upper_limit="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Days to Best Response From Start of Study to Initial Achievement of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)</title>
        <description>Time to Best Response is defined as time (days) from start of study to initial achievement of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
        <time_frame>At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)</time_frame>
        <population>Includes all participants that received treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia</title>
            <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).</description>
          </group>
        </group_list>
        <measure>
          <title>Median Days to Best Response From Start of Study to Initial Achievement of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)</title>
          <description>Time to Best Response is defined as time (days) from start of study to initial achievement of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
          <population>Includes all participants that received treatment.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42" lower_limit="39" upper_limit="159"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Duration (Days) of Response From Initial Achievement of Response to Loss of Response (mCR, mCRi, CR, CRi, PR, or SD)</title>
        <description>To determine duration (days) of response as defined as time from initial achievement of response to loss of response (mCR, mCRi, CR, CRi, PR, or SD).&#xD;
Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
        <time_frame>At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)</time_frame>
        <population>Includes all participants that received treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia</title>
            <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).</description>
          </group>
        </group_list>
        <measure>
          <title>Median Duration (Days) of Response From Initial Achievement of Response to Loss of Response (mCR, mCRi, CR, CRi, PR, or SD)</title>
          <description>To determine duration (days) of response as defined as time from initial achievement of response to loss of response (mCR, mCRi, CR, CRi, PR, or SD).&#xD;
Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
          <population>Includes all participants that received treatment.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="148" lower_limit="12" upper_limit="337"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Duration (Days) of Best Response From Initial Achievement of Best Response to Loss of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)</title>
        <description>Duration of Best Response is time (days) from initial achievement of best response to loss of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
        <time_frame>At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)</time_frame>
        <population>Includes all participants that received treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia</title>
            <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).</description>
          </group>
        </group_list>
        <measure>
          <title>Median Duration (Days) of Best Response From Initial Achievement of Best Response to Loss of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)</title>
          <description>Duration of Best Response is time (days) from initial achievement of best response to loss of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, &lt; 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, &lt; 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be &lt; 1,000/mcl and/or platelet count &lt; 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count &gt; 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt; 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.</description>
          <population>Includes all participants that received treatment.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="148" lower_limit="12" upper_limit="316"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Number of participants overall survival is defined as death from any cause</description>
        <time_frame>from enrollment until date of death, assessed up to 24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia</title>
            <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Number of participants overall survival is defined as death from any cause</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="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 weeks</time_frame>
      <desc>The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia</title>
          <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory AML.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.03)</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="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Wound infection bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood culture positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.03)</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="10" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Increased tendency to bruise</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cardiomegaly</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes insipidus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Thyroid mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eye symptom</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Myopia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nystagmus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Anorectal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fecal incontinence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lip ulceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral mucosal blistering</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Perirectal abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Generalised oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Head discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vascular access complication</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vessel puncture site bruise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatomegaly</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Enterococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Infections and infestations- Other, specify- Bacteremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Post-operative hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin wound</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tendonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood thyroid stimulating hormone increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood urine present</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Body temperature increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT corrected interval prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Heart rate irregular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Imaging procedure abnormal</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Surgical and medical procedures - Other, specify- Skin biopsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia nervosa</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tenosynovitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Bartholin's cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Haemangioma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Renal cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Altered state of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Micturition urgency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Polyuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema genital</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vulvovaginal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Bronchial wall thickening</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lung infiltration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pulmonary edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders- Bronchiectasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Photosensitivity reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Mucositis management</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Extremity necrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Intracranial hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </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>
    <limitations_and_caveats>The 5 patients who did not complete the study were for reason other than treatment related toxicities.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Christopher Hourigan</name_or_title>
      <organization>National Heart Lung and Blood Institute</organization>
      <phone>+1 301 451 0257</phone>
      <email>christopher.hourigan@nih.gov</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/NCT02996474
org study id: 170026
secondary id: 17-H-0026
nct id: NCT02996474
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Background:

      Acute myeloid leukemia (AML) is a cancer of the white blood cells. It is fatal if not
      treated. Treatment for AML that has not responded to treatment (refractory) or has returned
      after treatment (relapsed) often do not work. Researchers want to see if an immunotherapy
      drug, combined with a less intense chemotherapy, may be able to help.

      Objective:

      To test if pembrolizumab, in combination with decitabine, is a possible treatment for people
      with relapsed or refractory AML.

      Eligibility:

      Adults 18 years of age and older with refractory AML or relapsed AML.

      Design:

      Participants will be first screened for eligibility.

      The study is counted in 21-day cycles. The initial phase of the study consists of 8 cycles.
      Participants may be in the study for up to 2 years if they are responding to the treatment.

      The first 3 weeks of treatment is usually done in the hospital. The rest may be done as an
      outpatient.

      Participants will get pembrolizumab at the beginning of each cycle through an IV.

      Participants will usually get decitabine by IV on days 8 12 and days 15 19 of every other
      cycle.

      Participants will give blood samples.

      Participants will have bone marrow exams. A needle will be inserted into the hip to extract
      cells from the bone marrow.

      Some participants may give a sample of saliva from the inside of their cheek.

      Some participants may give a small skin sample. The top layer of the skin is removed.

      Some patients may require leukapheresis before starting treatment. This is a procedure to
      remove leukemia cells in the blood stream.
This is a pilot study to determine the feasibility of a novel combination of Pembrolizumab
      and Decitabine in relapsed/refractory adult AML patients. While both Pembrolizumab and
      Decitabine are FDA approved agents, this study will explore giving these drugs in combination
      for this population of patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility of a Novel Combination of Pembrolizumab and Decitabine in Relapsed/Refractory Acute Myeloid Leukemia Participants
time frame: 24 weeks
description: The number of patients who could be treated with a novel combination of Pembrolizumab and Decitabine in relapsed/refractory Acute Myeloid Leukemia participants without being removed from the protocol due to treatment related toxicities.
measure: Median Days to First Response From Start of Study to Initial Achievement of First Response (mCR, mCRi, CR, CRi, PR, or SD)
time frame: At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)
description: Time to first response (days) is time from start of study to first response (mCR, mCRi, CR, CRi, PR, or SD) in relapsed/refractory acute myeloid leukemia (AML) participants.
Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, < 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, < 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be < 1,000/mcl and/or platelet count < 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count > 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts < 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.
measure: Median Days to Best Response From Start of Study to Initial Achievement of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)
time frame: At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)
description: Time to Best Response is defined as time (days) from start of study to initial achievement of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, < 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, < 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be < 1,000/mcl and/or platelet count < 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count > 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts < 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.
measure: Median Duration (Days) of Response From Initial Achievement of Response to Loss of Response (mCR, mCRi, CR, CRi, PR, or SD)
time frame: At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)
description: To determine duration (days) of response as defined as time from initial achievement of response to loss of response (mCR, mCRi, CR, CRi, PR, or SD).
Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, < 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, < 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be < 1,000/mcl and/or platelet count < 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count > 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts < 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.
measure: Median Duration (Days) of Best Response From Initial Achievement of Best Response to Loss of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)
time frame: At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)
description: Duration of Best Response is time (days) from initial achievement of best response to loss of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, < 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, < 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be < 1,000/mcl and/or platelet count < 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count > 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts < 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.
measure: Overall Survival
time frame: from enrollment until date of death, assessed up to 24 weeks
description: Number of participants overall survival is defined as death from any cause
arm group label: Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia
arm group type: Experimental
description: Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory AML.
intervention type: Drug
intervention name: Pembrolizumab
description: 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Every effort should be made to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min).
arm group label: Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia
other name: Keytruda
other name: MK-3475
intervention type: Drug
intervention name: Decitabine
description: Will be administered at a dose of 20 mg/m^2 by continuous intravenous infusion over 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7). Decitabine should be repeated every 6 weeks.
arm group label: Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia
other name: Dacogen
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Christopher S Hourigan, M.D.
role: Principal Investigator
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-H-0026.html
description: NIH Clinical Center Detailed Web Page
citation: Goswami M, Gui G, Dillon LW, Lindblad KE, Thompson J, Valdez J, Kim DY, Ghannam JY, Oetjen KA, Destefano CB, Smith DM, Tekleab H, Li Y, Dagur P, Hughes T, Marte JL, Del Rivero J, Klubo-Gwiezdzinksa J, Gulley JL, Calvo KR, Lai C, Hourigan CS. Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia. J Immunother Cancer. 2022 Jan;10(1):e003392. doi: 10.1136/jitc-2021-003392.
PMID: 35017151
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Pembrolizumab
mesh term: Decitabine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The 5 patients who did not complete the study were for reason other than treatment related toxicities.
point of contact: 