<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/NCT02981914</url>
  </required_header>
  <id_info>
    <org_study_id>IRB16-1195</org_study_id>
    <nct_id>NCT02981914</nct_id>
  </id_info>
  <brief_title>Pilot Study of Pembrolizumab Treatment for Disease Relapse After Allogeneic Stem Cell Transplantation</brief_title>
  <official_title>Pilot Study of Pembrolizumab Treatment for Disease Relapse After Allogeneic Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Chicago</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>
      This pilot study has been designed to investigate the safety of pembrolizumab treatment for&#xD;
      disease relapse following allogeneic stem cell transplant (alloSCT). Pembrolizumab will be&#xD;
      administered at a fixed dose of 200 mg IV every 3 weeks. Approximately 12-26 patients with&#xD;
      relapsed MDS, AML, or mature B cell (B-NHL, cHL) malignancies that have relapsed following&#xD;
      alloSCT will be enrolled on this trial. Pembrolizumab treatment will be administered for up&#xD;
      to 24 months, provided that neither disease progression, nor development of a dose-limiting&#xD;
      toxicity (DLT), has occurred. Adverse events will be monitored every three weeks throughout&#xD;
      the trial and graded in severity according to the guidelines outlined in the NCI Common&#xD;
      Terminology Criteria for Adverse Events (CTCAE) version 4.0. This trial will be conducted in&#xD;
      accordance with Good Clinical Practices.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 7, 2017</start_date>
  <completion_date type="Anticipated">February 2029</completion_date>
  <primary_completion_date type="Anticipated">February 2023</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>Number of patients with adverse events</measure>
    <time_frame>24 months</time_frame>
    <description>To determine the tolerability of pembrolizumab treatment in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time between initial response and subsequent disease progression or relapse</measure>
    <time_frame>From date of therapy until the date of first documented progression or relapse, whichever came first, assessed up to 100 months</time_frame>
    <description>To determine the duration of response (DOR) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time between first documentation of complete remission (CR) or partial remission (PR) (by IRC) to the first documentation of disease progression or death by any cause</measure>
    <time_frame>From the date of first documented of CR or PR to the first documented progression or date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
    <description>To determine the overall response rate (ORR) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT, stratified by disease type.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time between the start of therapy to death from any cause.</measure>
    <time_frame>From start date of therapy to the date of death from any cause, whichever may come first, assessed up to 100 months</time_frame>
    <description>To determine the overall survival (OS) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Effect on restoring donor chimerism</measure>
    <time_frame>24 months</time_frame>
    <description>To determine the effect of pembrolizumab on restoring donor chimerism in patients with relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of pembrolizumab on the numbers and activations status of peripheral blood T cells</measure>
    <time_frame>24 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Compare PD-L1 expression on malignant cells at initial diagnosis and at disease relapse following alloSCT</measure>
    <time_frame>24 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Effect of pembrolizumab on the T cell receptor (TCR) repertoire in the peripheral blood, and where available, tumor environment, following alloSCT</measure>
    <time_frame>24 months</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">26</enrollment>
  <condition>Classical Hodgkin Lymphoma</condition>
  <condition>B-cell Non-Hodgkin Lymphoma</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks. Treatment will be administered for up to 24 months, provided that neither disease progression, nor development of a dose-limiting toxicity (DLT), has occurred.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks for a max of 24 months, so long as there is no disease progression.</description>
    <arm_group_label>Pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects with AML, MDS or mature B cell lymphomas that have relapsed&#xD;
             following matched-related donor (MRD) or matched unrelated donor (MUD) (HLA-A -B -C&#xD;
             -DR -DQ) alloSCT are eligible for enrollment&#xD;
&#xD;
               1. Signed written informed consent&#xD;
&#xD;
                    1. Subjects must have signed and dated an IRB-approved written informed consent&#xD;
                       form in accordance with regulatory and institutional guidelines. This must&#xD;
                       be obtained before the performance of any protocol-related procedures that&#xD;
                       are not part of normal subject care.&#xD;
&#xD;
                    2. Subjects must be willing and able to comply with scheduled visits, treatment&#xD;
                       schedule, laboratory tests and other requirements of the study.&#xD;
&#xD;
               2. Target population&#xD;
&#xD;
                    1. Subjects must be ≥ 18 years of age.&#xD;
&#xD;
                    2. Subjects must have an ECOG performance status of 0-1 (Appendix).&#xD;
&#xD;
                    3. Subjects have undergone alloSCT &gt; 90 days prior to enrollment from a&#xD;
                       matched-related donor (MRD), matched-unrelated donor (MUD), cord blood&#xD;
                       donor, or haplo-identical and cord blood donor.&#xD;
&#xD;
                    4. There must be histological confirmation of relapse after alloSCT of any of&#xD;
                       the following diseases: any mature B cell lymphoma (cHL or NHL), AML or MDS.&#xD;
&#xD;
                    5. Subjects must be off of all immunosuppressive medications for a minimum of 2&#xD;
                       weeks with the exception of physiologic doses of corticosteroids.&#xD;
&#xD;
                    6. Subjects with B cell lymphoma must have measurable disease, defined as at&#xD;
                       least 1 lesion that can be accurately measured in at least 2 dimensions with&#xD;
                       CT scan. Minimum measurement must be &gt; 15 mm in the longest diameter and &gt;&#xD;
                       10 mm in the short axis.&#xD;
&#xD;
                    7. Subjects must not have had any prior investigational agents or devices&#xD;
                       within 4 weeks of beginning study drug&#xD;
&#xD;
                    8. Subjects must have no prior history of VOD&#xD;
&#xD;
                    9. Subjects must demonstrate adequate organ function as defined below. All&#xD;
                       screening labs should be performed within 10 days of treatment initiation.&#xD;
&#xD;
                       Hematological Absolute neutrophil count (ANC) ≥ 500 /mcL Platelets ≥ 20,000&#xD;
                       /mcL Hemoglobin ≥ 8 g/dL (RBC transfusions are OK)&#xD;
&#xD;
                       Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR&#xD;
                       can also be used in place of creatinine or CrCl) ≤ 1.5 X upper limit of&#xD;
                       normal (ULN) or&#xD;
&#xD;
                         -  60 mL/min for subject with creatinine levels &gt; 1.5 X institutional ULN&#xD;
&#xD;
                       Hepatic Serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for&#xD;
                       subjects with total bilirubin levels &gt; 1.5X ULN AST (SGOT) and ALT (SGPT) ≤&#xD;
                       2.5 X ULN Albumin ≥ 2.0 mg/dL&#xD;
&#xD;
                       Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤&#xD;
                       1.5 X ULN unless subject is receiving anticoagulant therapy, in which case,&#xD;
                       the PT/INR should be within therapeutic range for intended use. Activated&#xD;
                       Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN unless subject is receiving&#xD;
                       anticoagulant therapy, in which case, the PTT should be within therapeutic&#xD;
                       range for intended use.&#xD;
&#xD;
                       *Creatinine clearance should be calculated per institutional standard.&#xD;
&#xD;
                   10. Female subjects of childbearing potential should have a negative urine or&#xD;
                       serum pregnancy test (β-hCG) within 72 hours prior to receiving the first&#xD;
                       dose of study medication.&#xD;
&#xD;
                   11. Female subjects with childbearing potential should be willing to use 2&#xD;
                       methods of contraception, be surgically sterile, or abstain from&#xD;
                       heterosexual activity throughout the course of the study, until 120 days&#xD;
                       after the final dose of study medication. Subjects with childbearing&#xD;
                       potential are those who have not been surgically sterilized or have not been&#xD;
                       free from menses for &gt; 1 year. Abstinence is acceptable if this is the&#xD;
                       established and preferred contraceptive method for the subject.&#xD;
&#xD;
                   12. Male subjects should agree to use an adequate method of contraception&#xD;
                       starting with the first dose of study medication until 120 days after the&#xD;
                       final dose of study medicine. Abstinence is acceptable if this is the&#xD;
                       established and preferred contraceptive method for the subject.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Target disease exclusions&#xD;
&#xD;
               1. Subjects must not have known central nervous system involvement by disease&#xD;
                  (parenchymal, meningeal or cerebrospinal fluid) 2. Medical history, concurrent&#xD;
                  diseases, and prior treatments&#xD;
&#xD;
               1. Subjects must not have a history of any positive test for hepatitis B or&#xD;
                  hepatitis C indicating active disease or previous exposure.&#xD;
&#xD;
               2. Subjects must not have a history of human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
               3. Subjects must not be receiving systemic steroid therapy or any other form of&#xD;
                  immunosuppressive therapy within 2 weeks prior to the first dose of study&#xD;
                  medication. The use of physiologic doses of corticosteroids is acceptable.&#xD;
&#xD;
               4. Subjects must not be concurrently receiving disease-modifying therapy in another&#xD;
                  therapeutic investigational study.&#xD;
&#xD;
               5. Subjects must not have received a prior monoclonal antibody within 4 weeks prior&#xD;
                  to the first dose of study medication, and must have recovered (≤ grade 1) from&#xD;
                  adverse events related to any anti-cancer agent administered &gt; 4 weeks previous&#xD;
                  to the first dose of study medication.&#xD;
&#xD;
               6. Subjects must not have received chemotherapy, targeted small molecule therapy, or&#xD;
                  radiation therapy within 2 weeks prior to the first dose of study medication, and&#xD;
                  must have recovered (≤ grade 1) from adverse events related to a previously&#xD;
                  administered agent.&#xD;
&#xD;
               7. Subjects must not have received a donor lymphocyte infusion (DLI) within 8 weeks&#xD;
                  prior to the first dose of study medication.&#xD;
&#xD;
               8. Subjects must not have a history of severe (grade 3-4) acute GVHD, and/or current&#xD;
                  &gt; grade 1 acute GHVD. Subjects must not have a history of chronic GVHD (whether&#xD;
                  limited or extensive stage).&#xD;
&#xD;
               9. Subjects must not have autoimmune disease that has required systemic treatment in&#xD;
                  the past 2 years (i.e. with use of disease modifying agents, corticosteroids or&#xD;
                  immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or&#xD;
                  physiologic corticosteroid replacement therapy for adrenal or pituitary&#xD;
                  insufficiency, etc.) is not considered a form of systemic treatment.&#xD;
&#xD;
              10. Subjects must not have a known history of congestive heart failure, unstable&#xD;
                  angina pectoris, or cardiac arrhythmia (with the exception of chronic and&#xD;
                  rate-controlled atrial fibrillation).&#xD;
&#xD;
              11. Subjects must not have a history of other serious underlying medical or&#xD;
                  psychiatric condition that, in the opinion of the investigator, would impair the&#xD;
                  ability to receive, tolerate and or comply with the planned treatment and&#xD;
                  follow-up.&#xD;
&#xD;
              12. Subjects must not have a history of a known secondary primary malignancy that is&#xD;
                  not in remission and/or that requires active therapy. Exceptions include&#xD;
                  non-melanoma skin cancers and in situ cervical cancer that has undergone&#xD;
                  curative-intent local therapy.&#xD;
&#xD;
              13. Subjects must not have a known active infection requiring intravenous antibiotic&#xD;
                  therapy.&#xD;
&#xD;
              14. Subjects must not have a history of (non-infectious) pneumonitis that required&#xD;
                  steroid treatment, evidence of interstitial lung disease, or active,&#xD;
                  non-infectious pneumonitis. Subjects must not have active, non-infectious&#xD;
                  colitis.&#xD;
&#xD;
              15. Subjects must not be pregnant or breastfeeding, or expecting to conceive or&#xD;
                  father children within the projected duration of the trial, starting with the&#xD;
                  screening visit through 120 days after the final dose of study medication.&#xD;
&#xD;
              16. Subjects must not have received a live vaccine within 30 days prior to the first&#xD;
                  dose of study medication.&#xD;
&#xD;
              17. Subjects must not be or have an immediate family member (spouse, parent, legal&#xD;
                  guardian, sibling or child) who is an investigational site sponsor or staff&#xD;
                  directly involved with the trial, unless IRB approval is granted previously.&#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>Justin Kline, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Chicago</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Michael Gomez</last_name>
    <phone>(773) 834-5314</phone>
    <email>mgomez9@medicine.bsd.uchicago.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexis Small</last_name>
      <phone>773-702-9440</phone>
      <email>asmall@medicine.bsd.uchicago.edu</email>
    </contact>
    <investigator>
      <last_name>Justin Kline, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>June 29, 2021</last_update_submitted>
  <last_update_submitted_qc>June 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Classical Hodgkin Lymphoma</keyword>
  <keyword>B-cell Non-Hodgkin Lymphoma</keyword>
  <keyword>Acute Myeloid Leukemia</keyword>
  <keyword>Myelodysplastic Syndromes</keyword>
  <keyword>pembrolizumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Hodgkin Disease</mesh_term>
    <mesh_term>Lymphoma, B-Cell</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>
  <pending_results>
    <submitted>November 23, 2022</submitted>
  </pending_results>
  <!-- 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/NCT02981914
org study id: IRB16-1195
nct id: NCT02981914
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This pilot study has been designed to investigate the safety of pembrolizumab treatment for
      disease relapse following allogeneic stem cell transplant (alloSCT). Pembrolizumab will be
      administered at a fixed dose of 200 mg IV every 3 weeks. Approximately 12-26 patients with
      relapsed MDS, AML, or mature B cell (B-NHL, cHL) malignancies that have relapsed following
      alloSCT will be enrolled on this trial. Pembrolizumab treatment will be administered for up
      to 24 months, provided that neither disease progression, nor development of a dose-limiting
      toxicity (DLT), has occurred. Adverse events will be monitored every three weeks throughout
      the trial and graded in severity according to the guidelines outlined in the NCI Common
      Terminology Criteria for Adverse Events (CTCAE) version 4.0. This trial will be conducted in
      accordance with Good Clinical Practices.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with adverse events
time frame: 24 months
description: To determine the tolerability of pembrolizumab treatment in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.
measure: Time between initial response and subsequent disease progression or relapse
time frame: From date of therapy until the date of first documented progression or relapse, whichever came first, assessed up to 100 months
description: To determine the duration of response (DOR) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.
measure: Time between first documentation of complete remission (CR) or partial remission (PR) (by IRC) to the first documentation of disease progression or death by any cause
time frame: From the date of first documented of CR or PR to the first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
description: To determine the overall response rate (ORR) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT, stratified by disease type.
measure: Time between the start of therapy to death from any cause.
time frame: From start date of therapy to the date of death from any cause, whichever may come first, assessed up to 100 months
description: To determine the overall survival (OS) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.
measure: Effect on restoring donor chimerism
time frame: 24 months
description: To determine the effect of pembrolizumab on restoring donor chimerism in patients with relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.
measure: Effect of pembrolizumab on the numbers and activations status of peripheral blood T cells
time frame: 24 months
measure: Compare PD-L1 expression on malignant cells at initial diagnosis and at disease relapse following alloSCT
time frame: 24 months
measure: Effect of pembrolizumab on the T cell receptor (TCR) repertoire in the peripheral blood, and where available, tumor environment, following alloSCT
time frame: 24 months
arm group label: Pembrolizumab
arm group type: Experimental
description: Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks. Treatment will be administered for up to 24 months, provided that neither disease progression, nor development of a dose-limiting toxicity (DLT), has occurred.
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks for a max of 24 months, so long as there is no disease progression.
arm group label: Pembrolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Justin Kline, MD
role: Principal Investigator
affiliation: University of Chicago
last name: Michael Gomez
phone: (773) 834-5314
email: mgomez9@medicine.bsd.uchicago.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Lymphoma, Non-Hodgkin
mesh term: Preleukemia
mesh term: Hodgkin Disease
mesh term: Lymphoma, B-Cell
mesh term: Myelodysplastic Syndromes
mesh term: Pembrolizumab
submitted: November 23, 2022