<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/NCT03291353</url>
  </required_header>
  <id_info>
    <org_study_id>17-056</org_study_id>
    <nct_id>NCT03291353</nct_id>
  </id_info>
  <brief_title>Phase 0- Pilot Study of Pembrolizumab on Immune Cells in Patient With Refractory Acute Myeloid Leukemia</brief_title>
  <official_title>Phase 0- Pilot Study of Pembrolizumab on Immune Cells in Patient With Refractory Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Michael Boyiadzis</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open label, single-arm, pilot trial to evaluate the immune effects, safety and&#xD;
      tolerability of pembrolizumab in subjects newly diagnosed with acute myeloid leukemia (AML)&#xD;
      who have persistent leukemia after induction chemotherapy. Patients must have an ECOG&#xD;
      performance status of 0-1. The enrollment target for this study is 10 patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    This study has closed due to slow accrual.&#xD;
  </why_stopped>
  <start_date type="Actual">October 17, 2017</start_date>
  <completion_date type="Anticipated">August 19, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 19, 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse event assessment</measure>
    <time_frame>From prior to first dose up to 48 months</time_frame>
    <description>Adverse event assessment using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response Rate (RR)</measure>
    <time_frame>Up to greater than or equal to 48 months</time_frame>
    <description>The number of patients receiving treatment that experience either a Partial Response (remission) and/or a Complete Response (remission) / the total number of treated patients, per Response Criteria for Acute Leukemia criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to greater than or equal to 48 months</time_frame>
    <description>Median overall survival will be estimated by the Kaplan-Meier method with 90% confidence intervals.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Percent change of neutrophils and lymphocytes</measure>
    <time_frame>Up to greater than or equal to 48 months</time_frame>
    <description>Percent change of neutrophils and lymphocytes from baseline before therapy to follow up</description>
  </other_outcome>
  <other_outcome>
    <measure>Absolute number of CD4+ T cells, CD8+ T cells, Treg , NK cells, B cells and monocytes</measure>
    <time_frame>Up to greater than or equal to 48 months</time_frame>
    <description>Change in number of CD4+ T cells, CD8+ T cells, Treg , NK cells, B cells and monocytes from baseline before therapy to follow up</description>
  </other_outcome>
  <other_outcome>
    <measure>Absolute number of activated immune effector cells</measure>
    <time_frame>Up to greater than or equal to 48 months</time_frame>
    <description>Change in number of activated immune effector cells from baseline before therapy to follow up</description>
  </other_outcome>
  <other_outcome>
    <measure>Levels of TGF-beta and NKG2D ligands</measure>
    <time_frame>Up to greater than or equal to 48 months</time_frame>
    <description>Change in level from baseline before therapy to follow up</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Refractory Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>AML Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>pembrolizumab 200 mg given IV once every three weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <description>200 mg IV given every three weeks</description>
    <arm_group_label>AML Patients</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Be willing and able to provide written informed consent/assent for the trial.&#xD;
&#xD;
          2. Be 18 years of age on the day of signing informed consent.&#xD;
&#xD;
          3. Patients with newly diagnosed AML based on the World Health Organization&#xD;
             classification (21) who have persistent leukemia after a course or more of treatment&#xD;
             with induction chemotherapy (the diagnosis of persistent disease, which is defined as&#xD;
             &gt;10% blasts by evaluation of bone marrow biopsy or bone marrow aspirate).&#xD;
&#xD;
          4. Left ventricular ejection fraction (LVEF) ≥ 45%&#xD;
&#xD;
          5. Have a performance status of 0 or 1 on the ECOG Performance Scale.&#xD;
&#xD;
          6. Demonstrate adequate organ function, all screening labs should be performed within 10&#xD;
             days of treatment initiation.&#xD;
&#xD;
          7. 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;
          8. 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.&#xD;
&#xD;
          9. Male subjects of childbearing potential must agree to use an adequate method of&#xD;
             contraception- Contraception, starting with the first dose of study therapy through&#xD;
             120 days after the last dose of study therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has a diagnosis of Acute Promyelocytic Leukemia (APL) as defined by the World Health&#xD;
             Organization&#xD;
&#xD;
          2. Relapsed acute myeloid leukemia&#xD;
&#xD;
          3. Bi-lineage or bi-phenotypic leukemias&#xD;
&#xD;
          4. Prior use of clofarabine or fludarabine&#xD;
&#xD;
          5. Previous allogeneic or autologous hematopoietic cell transplantation or solid organ&#xD;
             transplantation&#xD;
&#xD;
          6. Is currently participating in and receiving study therapy, or has participated in a&#xD;
             study of an investigational agent and received study therapy, or used an&#xD;
             investigational device within 4 weeks of the first dose of treatment.&#xD;
&#xD;
          7. 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;
          8. Has a known history of active TB (Bacillus Tuberculosis)&#xD;
&#xD;
          9. Hypersensitivity to pembrolizumab or any of its excipients.&#xD;
&#xD;
         10. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study&#xD;
             Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events&#xD;
             due to agents administered more than 4 weeks earlier.&#xD;
&#xD;
         11. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy&#xD;
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at&#xD;
             baseline) from adverse events due to a previously administered agent.&#xD;
&#xD;
         12. Concurrent active malignancy; exceptions include patients who have been disease free&#xD;
             for 5 years, patients with a history of completely resected non-melanoma skin cancer&#xD;
             or successfully treated in situ carcinoma, or patients with another malignancy that is&#xD;
             indolent or definitively treated.&#xD;
&#xD;
         13. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis and/or has known active central nervous system (CNS) leukemia involvement.&#xD;
&#xD;
         14. 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;
         15. Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis.&#xD;
&#xD;
         16. 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;
         17. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
         18. 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;
         19. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.&#xD;
&#xD;
         20. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
         21. Has known active Hepatitis B or Hepatitis C.&#xD;
&#xD;
         22. Has received a live vaccine within 30 days of planned start of study therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Boyiadzis, MD, MHSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>June 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>April 17, 2019</last_update_submitted>
  <last_update_submitted_qc>April 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Michael Boyiadzis</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03291353
org study id: 17-056
nct id: NCT03291353
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an open label, single-arm, pilot trial to evaluate the immune effects, safety and
      tolerability of pembrolizumab in subjects newly diagnosed with acute myeloid leukemia (AML)
      who have persistent leukemia after induction chemotherapy. Patients must have an ECOG
      performance status of 0-1. The enrollment target for this study is 10 patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse event assessment
time frame: From prior to first dose up to 48 months
description: Adverse event assessment using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
measure: Response Rate (RR)
time frame: Up to greater than or equal to 48 months
description: The number of patients receiving treatment that experience either a Partial Response (remission) and/or a Complete Response (remission) / the total number of treated patients, per Response Criteria for Acute Leukemia criteria.
measure: Overall survival
time frame: Up to greater than or equal to 48 months
description: Median overall survival will be estimated by the Kaplan-Meier method with 90% confidence intervals.
measure: Percent change of neutrophils and lymphocytes
time frame: Up to greater than or equal to 48 months
description: Percent change of neutrophils and lymphocytes from baseline before therapy to follow up
measure: Absolute number of CD4+ T cells, CD8+ T cells, Treg , NK cells, B cells and monocytes
time frame: Up to greater than or equal to 48 months
description: Change in number of CD4+ T cells, CD8+ T cells, Treg , NK cells, B cells and monocytes from baseline before therapy to follow up
measure: Absolute number of activated immune effector cells
time frame: Up to greater than or equal to 48 months
description: Change in number of activated immune effector cells from baseline before therapy to follow up
measure: Levels of TGF-beta and NKG2D ligands
time frame: Up to greater than or equal to 48 months
description: Change in level from baseline before therapy to follow up
arm group label: AML Patients
arm group type: Experimental
description: pembrolizumab 200 mg given IV once every three weeks
intervention type: Drug
intervention name: pembrolizumab
description: 200 mg IV given every three weeks
arm group label: AML Patients
other name: Keytruda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Boyiadzis, MD, MHSc
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Michael Boyiadzis
investigator title: Associate Professor of Medicine
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Pembrolizumab