<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/NCT03286114</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2017.056</org_study_id>
    <secondary_id>HUM00129255</secondary_id>
    <nct_id>NCT03286114</nct_id>
  </id_info>
  <brief_title>Augmentation of the Graft vs. Leukemia Effect Via Checkpoint Blockade With Pembrolizumab</brief_title>
  <official_title>Augmentation of the Graft vs. Leukemia Effect Via Checkpoint Blockade With Pembrolizumab for Relapse of Primary Malignancy After Allogeneic Hematopoietic Stem Cell Transplant: A Feasibility Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan Rogel Cancer Center</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single arm, open-label, Phase 1b study of pembrolizumab for patients with&#xD;
      myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic&#xD;
      leukemia (ALL) whose disease has relapsed after receiving allogeneic hematopoetic stem cell&#xD;
      transplant.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of patient population&#xD;
  </why_stopped>
  <start_date type="Actual">December 21, 2017</start_date>
  <completion_date type="Actual">April 28, 2021</completion_date>
  <primary_completion_date type="Actual">October 22, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The number of patients that demonstrate clinical benefit from treatment</measure>
    <time_frame>Day 77</time_frame>
    <description>This study will assess if the study drug is promising for further study. The study drug will be considered promising if at least 4 patients receive a clinical benefit or if any complete response is seen. Clinical benefit is defined as either stable disease, partial remission or complete remission to treatment.&#xD;
Complete remission (CR) will be defined as achieving a morphologic leukemia free state by achieving all of the following criteria: bone marrow myeloblasts &lt; 5% by morphologic assessment; AND absence of circulating blasts with phenotypic or morphologic features of leukemia (e.g. Auer rods) AND no evidence of extramedulary disease.&#xD;
Partial remission (PR) will be defined as a ≥ 50% reduction in bone marrow blast percentage to 5-25% or marrow blasts &lt; 5% with persistent Auer rods, flow cytometric or cytogenetic disease.&#xD;
SD will be defined as ≤ 5% increase in blasts or decreased blast percentage in the bone marrow that does not meet the criteria for PR.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The number of patients that respond to treatment</measure>
    <time_frame>Day 77</time_frame>
    <description>This study will assess the number of patients that respond to treatment by overall response rate (ORR). ORR is defined as the number of patients will complete remission and partial remission.&#xD;
Complete remission (CR) will be defined as achieving a morphologic leukemia free state by achieving all of the following criteria: bone marrow myeloblasts &lt; 5% by morphologic assessment; AND absence of circulating blasts with phenotypic or morphologic features of leukemia (e.g. Auer rods) AND no evidence of extramedulary disease.&#xD;
Partial remission (PR) will be defined as a ≥ 50% reduction in bone marrow blast percentage to 5-25% or marrow blasts &lt; 5% with persistent Auer rods, flow cytometric or cytogenetic disease.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The number of patients that experience Graft Versus Host Disease (GvHD) or other significant immune mediated toxicities</measure>
    <time_frame>30 Days Post Treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The number of patients alive at 1 year</measure>
    <time_frame>1 Year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of patients alive at 1 year without disease</measure>
    <time_frame>1 Year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Myelodysplastic Syndromes</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>200mg IV every 21 days</description>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <other_name>KEYTRUDA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL) or Myelodysplastic&#xD;
             Syndrome (MDS) in confirmed relapse&#xD;
&#xD;
          -  Confirmation of 'measurable disease'&#xD;
&#xD;
          -  Patient may not have received definitive salvage chemotherapy for their&#xD;
             post-transplant relapse within the past 21 days.&#xD;
&#xD;
          -  Be willing and able to provide written informed consent/assent for the trial&#xD;
&#xD;
          -  Be ≥ 18 years of age on day of signing informed consent&#xD;
&#xD;
          -  Be willing to provide tissue from bone marrow biopsies&#xD;
&#xD;
          -  Have a performance status of 0, to 1 on the ECOG Performance Scale. Eastern&#xD;
             Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients'&#xD;
             general well-being and activities of daily life. The score ranges from 0 to 5 where 0&#xD;
             is asymptomatic and 5 is death.&#xD;
&#xD;
          -  Demonstrate adequate organ function&#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.&#xD;
&#xD;
          -  Female subjects of childbearing potential must be willing to use an adequate method of&#xD;
             contraception&#xD;
&#xD;
          -  Male subjects of childbearing potential must agree to use an adequate method of&#xD;
             contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has had relapse prior to primary neutrophil engraftment or ≤21 days post HCT.&#xD;
&#xD;
          -  Has received &gt;1 line of chemotherapy or other treatment directed towards&#xD;
             post-transplant relapse prior to study entry&#xD;
&#xD;
          -  Rapidly progressive relapse requiring urgent chemotherapy as determined by treating&#xD;
             physician&#xD;
&#xD;
          -  Is currently participating and receiving study therapy of an investigational agent and&#xD;
             received study therapy within 2 weeks of the first dose of treatment.&#xD;
&#xD;
          -  Has a diagnosis of active GvHD (≥ Grade I)&#xD;
&#xD;
          -  Receiving systemic steroid therapy of &gt; 10mg prednisone daily or equivalent*&#xD;
&#xD;
          -  Has received GM-CSF within 14 days of first dose of pembrolizumab&#xD;
&#xD;
          -  Has a known history of active TB (Bacillus Tuberculosis)Hypersensitivity to&#xD;
             pembrolizumab or any of its excipients&#xD;
&#xD;
          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study&#xD;
             Day 1 or who has not recovered from adverse events&#xD;
&#xD;
          -  Has had prior chemotherapy within 21 days or radiation therapy within 14 days prior to&#xD;
             study Day 1 or who has not recovered from adverse events&#xD;
&#xD;
          -  Has a known additional (secondary) malignancy that is progressing or requires active&#xD;
             treatment&#xD;
&#xD;
          -  Has known or suspected active central nervous system (CNS) metastases and/or&#xD;
             carcinomatous meningitis&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids, or current&#xD;
             pneumonitis&#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&#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)&#xD;
&#xD;
          -  Has known active Hepatitis B or Hepatitis C&#xD;
&#xD;
          -  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>John Magenau, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Rogel Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03286114
org study id: UMCC 2017.056
secondary id: HUM00129255
nct id: NCT03286114
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a single arm, open-label, Phase 1b study of pembrolizumab for patients with
      myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic
      leukemia (ALL) whose disease has relapsed after receiving allogeneic hematopoetic stem cell
      transplant.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The number of patients that demonstrate clinical benefit from treatment
time frame: Day 77
description: This study will assess if the study drug is promising for further study. The study drug will be considered promising if at least 4 patients receive a clinical benefit or if any complete response is seen. Clinical benefit is defined as either stable disease, partial remission or complete remission to treatment.
Complete remission (CR) will be defined as achieving a morphologic leukemia free state by achieving all of the following criteria: bone marrow myeloblasts < 5% by morphologic assessment; AND absence of circulating blasts with phenotypic or morphologic features of leukemia (e.g. Auer rods) AND no evidence of extramedulary disease.
Partial remission (PR) will be defined as a ≥ 50% reduction in bone marrow blast percentage to 5-25% or marrow blasts < 5% with persistent Auer rods, flow cytometric or cytogenetic disease.
SD will be defined as ≤ 5% increase in blasts or decreased blast percentage in the bone marrow that does not meet the criteria for PR.
measure: The number of patients that respond to treatment
time frame: Day 77
description: This study will assess the number of patients that respond to treatment by overall response rate (ORR). ORR is defined as the number of patients will complete remission and partial remission.
Complete remission (CR) will be defined as achieving a morphologic leukemia free state by achieving all of the following criteria: bone marrow myeloblasts < 5% by morphologic assessment; AND absence of circulating blasts with phenotypic or morphologic features of leukemia (e.g. Auer rods) AND no evidence of extramedulary disease.
Partial remission (PR) will be defined as a ≥ 50% reduction in bone marrow blast percentage to 5-25% or marrow blasts < 5% with persistent Auer rods, flow cytometric or cytogenetic disease.
measure: The number of patients that experience Graft Versus Host Disease (GvHD) or other significant immune mediated toxicities
time frame: 30 Days Post Treatment
measure: The number of patients alive at 1 year
time frame: 1 Year
measure: The number of patients alive at 1 year without disease
time frame: 1 Year
arm group label: Pembrolizumab
arm group type: Experimental
intervention type: Drug
intervention name: Pembrolizumab
description: 200mg IV every 21 days
arm group label: Pembrolizumab
other name: KEYTRUDA
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John Magenau, M.D.
role: Principal Investigator
affiliation: University of Michigan Rogel Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Myelodysplastic Syndromes
mesh term: Pembrolizumab
sharing ipd: Undecided