<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/NCT02243579</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2014-00709</org_study_id>
    <secondary_id>NCI-2014-00709</secondary_id>
    <secondary_id>CITN-10</secondary_id>
    <secondary_id>CITN-10</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <secondary_id>U01CA154967</secondary_id>
    <nct_id>NCT02243579</nct_id>
  </id_info>
  <brief_title>Pembrolizumab in Treating Patients With Relapsed or Refractory Stage IB-IVB Mycosis Fungoides or Sezary Syndrome</brief_title>
  <official_title>A Phase 2 Study of MK-3475 for the Treatment of Relapsed/Refractory Mycosis Fungoides/Sezary Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well pembrolizumab works in treating patients with stage&#xD;
      IB-IVB mycosis fungoides or Sezary syndrome that has returned after a period of improvement&#xD;
      or has not responded to at least one type of treatment. Monoclonal antibodies, such as&#xD;
      pembrolizumab, may block cancer growth in different ways by targeting certain cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the response rate of MK-3475 (pembrolizumab) in subjects with&#xD;
      relapsed/refractory mycosis fungoides/Sezary syndrome (MF/SS).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To explore the clinical activity of MK-3475 in subjects with relapsed/refractory MF and SS&#xD;
      with respect to the following endpoints: duration of response (DOR); progression-free&#xD;
      survival (PFS); overall survival (OS).&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat&#xD;
      every 3 weeks for up to 2 years (6 months for patients achieving complete response [CR]) in&#xD;
      the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 30 days and then every 12&#xD;
      weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2014</start_date>
  <completion_date type="Actual">April 1, 2019</completion_date>
  <primary_completion_date type="Actual">January 4, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome</measure>
    <time_frame>Up to 3.2 years</time_frame>
    <description>A generalized linear model for the objective response rate used a binominal error distribution. The model included as covariates all available baseline predictors of the missing outcomes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard Mycosis Fungoides and Sezary Syndrome response criteria, assessed at 26 and 52 weeks</time_frame>
    <description>Was estimated using the Kaplan-Meier method (Duration of Response Probability).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed at 26 and 52 weeks</time_frame>
    <description>Was estimated using the Kaplan-Meier method (Progression Free Survival Probability).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>The time from randomization to death due to any cause, assessed at 52, 104 and 156 weeks</time_frame>
    <description>Was estimated using the Kaplan-Meier method (Overall Survival Probability).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Onset of First Drug-related Toxicity</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Summary statistics (mean and SD) for time to onset of first drug-related toxicity was provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events Graded Using the Common Terminology Criteria for Adverse Events Version 5.0</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Adverse events were summarized as counts and frequencies by toxicity grade.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Recurrent Mycosis Fungoides and Sezary Syndrome</condition>
  <condition>Refractory Mycosis Fungoides and Sezary Syndrome</condition>
  <condition>Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7</condition>
  <condition>Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7</condition>
  <condition>Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7</condition>
  <condition>Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7</condition>
  <condition>Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v7</condition>
  <condition>Stage IVA Mycosis Fungoides and Sezary Syndrome AJCC v7</condition>
  <condition>Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v7</condition>
  <arm_group>
    <arm_group_label>Treatment (pembrolizumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (pembrolizumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pembrolizumab)</arm_group_label>
    <other_name>Keytruda</other_name>
    <other_name>Lambrolizumab</other_name>
    <other_name>MK-3475</other_name>
    <other_name>SCH 900475</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  This trial will include subjects with stage IB-IVB MF/SS (maximal stage since&#xD;
             diagnosis will determine eligibility), and who have relapsed, are refractory, or&#xD;
             progressed after at least one standard systemic therapy; current disease stage at time&#xD;
             of entry will also be documented but will not be used for eligibility&#xD;
&#xD;
          -  Subjects must have the following minimum wash-out and adverse event (AE) recovery&#xD;
             period from previous treatments without treatment between documentation of&#xD;
             relapse/progression and enrollment of specifically:&#xD;
&#xD;
               -  &gt;= 2 weeks for local radiation therapy&#xD;
&#xD;
               -  &gt;= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational&#xD;
                  agents that are not defined as immunotherapy, or for tumor-targeting monoclonal&#xD;
                  antibodies (mAbs) with the exception of alemtuzumab for which the washout is at&#xD;
                  least 8 weeks&#xD;
&#xD;
               -  &gt;= 15 weeks for anti-cluster of differentiation (CD)137 or anti-cytotoxic&#xD;
                  T-lymphocyte-associated protein 4 (CTLA-4) (including ipilimumab or any other&#xD;
                  antibody or drug specifically targeting T-cell co-stimulation or checkpoint&#xD;
                  pathways)&#xD;
&#xD;
               -  &gt;= 2 weeks from resolution (i.e., =&lt; grade 1 or at baseline) from AEs due to&#xD;
                  procedures performed or therapeutic agents administered&#xD;
&#xD;
               -  &gt;= 2 weeks for retinoids, interferons, vorinostat, romidepsin, denileukin&#xD;
                  diftitox, and therapeutic doses of oral corticosteroids (physiologic replacement&#xD;
                  doses of oral corticosteroids are allowed, topical corticosteroids are allowed)&#xD;
&#xD;
               -  &gt;= 2 weeks for phototherapy&#xD;
&#xD;
               -  &gt;= 1 week for topical therapy (including retinoid, nitrogen mustard, or&#xD;
                  imiquimod)&#xD;
&#xD;
          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)&#xD;
             performance scale&#xD;
&#xD;
          -  Life expectancy of at least 6 months&#xD;
&#xD;
          -  Performed within 10 days of treatment initiation: Leukocytes &gt;= 2,000/mcL&#xD;
&#xD;
          -  Performed within 10 days of treatment initiation: Absolute neutrophil count &gt;=&#xD;
             1,500/mcL&#xD;
&#xD;
          -  Performed within 10 days of treatment initiation: Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Performed within 10 days of treatment initiation: Hemoglobin &gt;= 9 g/dL OR &gt;= 5.6&#xD;
             mmol/L&#xD;
&#xD;
          -  Performed within 10 days of treatment initiation: Serum total bilirubin =&lt; 1.5 x upper&#xD;
             limit of normal (ULN) OR direct bilirubin =&lt; ULN for subjects with total bilirubin&#xD;
             levels &gt; 1.5 ULN&#xD;
&#xD;
          -  Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)&#xD;
             (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)&#xD;
             (serum glutamate pyruvate transaminase [SGPT]) =&lt; 2.5 x ULN OR =&lt; 5 x ULN for patients&#xD;
             with liver metastases&#xD;
&#xD;
          -  Performed within 10 days of treatment initiation: Serum creatinine =&lt; 1.5 x ULN OR&#xD;
             measured or calculated creatinine clearance &gt;= 60 mL/min for subject with creatinine&#xD;
             clearance (CrCl) levels &gt; 1.5 x institutional ULN (glomerular filtration rate [GFR]&#xD;
             can also be used in place of creatinine or CrCl)&#xD;
&#xD;
          -  Performed within 10 days of treatment initiation: International normalized ratio (INR)&#xD;
             or prothrombin time (PT) =&lt; 1.5 x ULN unless subject is receiving anticoagulant&#xD;
             therapy in which case the INR or PT must be within the therapeutic range of intended&#xD;
             use for the anticoagulant&#xD;
&#xD;
          -  Performed within 10 days of treatment initiation: Activated partial thromboplastin&#xD;
             time (aPTT) =&lt; 1.5 x ULN unless subject is receiving anticoagulant therapy in which&#xD;
             case the aPTT must be within the therapeutic range of intended use for the&#xD;
             anticoagulant&#xD;
&#xD;
          -  Performed within 10 days of treatment initiation: Thyroid stimulating hormone (TSH)&#xD;
             within institutional limits (ie: normal); if TSH is greater or less than institutional&#xD;
             limits patients may participate if their thyroxine (T4) is within normal limits (WNL);&#xD;
             patients may be on a stable dose of replacement thyroid medication; dose adjustments&#xD;
             are allowed if needed&#xD;
&#xD;
          -  Patients must provide tissue from a punch biopsy of the skin at baseline, at the time&#xD;
             of a clinical event (at the time of response, progression or appearance of a new&#xD;
             lesion) and at the end of treatment; additional punch biopsies every 3 cycles are&#xD;
             optional; an archival tissue sample is optional&#xD;
&#xD;
          -  Have measurable disease based on modified severity-weighted assessment tool (mSWAT);&#xD;
             tumor lesions situated in a previously irradiated area are considered measurable if&#xD;
             progression has been demonstrated in such lesions&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) from the time of the&#xD;
             pre-study visit, through the course of the study and for 120 days after the last dose&#xD;
             of study medication&#xD;
&#xD;
               -  Female patients 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;
                  if the urine test is positive or cannot be confirmed as negative, a serum&#xD;
                  pregnancy test will be required&#xD;
&#xD;
               -  Female patients of childbearing potential should be willing to use 2 methods of&#xD;
                  birth control or be surgically sterile, or abstain from heterosexual activity&#xD;
                  from the time of the pre-study visit, through the course of the study and for 120&#xD;
                  days after the last dose of study medication; patients of childbearing potential&#xD;
                  are those who have not been surgically sterilized or have not been free from&#xD;
                  menses for &gt; 1 year&#xD;
&#xD;
               -  Should a woman become pregnant or suspect she is pregnant while she is&#xD;
                  participating in this study, she should inform her treating physician&#xD;
                  immediately; men treated or enrolled on this protocol must also agree to use&#xD;
                  adequate contraception prior to the study, for the duration of study&#xD;
                  participation, and 4 months after completion of MK-3475 administration&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks&#xD;
             (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who&#xD;
             have not recovered from adverse events due to agents administered more than 4 weeks&#xD;
             earlier&#xD;
&#xD;
               -  Note: patients with =&lt; grade 2 neuropathy are an exception to this criterion and&#xD;
                  may qualify for the study&#xD;
&#xD;
               -  Note: if patients received major surgery, they must have recovered adequately&#xD;
                  from the toxicity and/or complications from the intervention prior to starting&#xD;
                  therapy&#xD;
&#xD;
          -  Patients who are currently participating in or have participated in a study of an&#xD;
             investigational agent or using an investigational device within 4 weeks of the first&#xD;
             dose of treatment&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving therapeutic systemic steroid&#xD;
             therapy or any other form of immunosuppressive therapy within 7 days prior to the&#xD;
             first dose of trial treatment&#xD;
&#xD;
          -  Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not&#xD;
             recovered (i.e., =&lt; grade 1 or at baseline) from AEs due to agents administered more&#xD;
             than 4 weeks earlier&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment;&#xD;
             exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the&#xD;
             skin, or in situ cervical cancer that has undergone potentially curative therapy&#xD;
&#xD;
          -  Patients with known brain metastases should be excluded from this clinical trial&#xD;
&#xD;
               -  Patients with carcinomatous meningitis should also be excluded&#xD;
&#xD;
               -  Patients with previously treated brain metastases may participate provided they&#xD;
                  are stable (without evidence of progression by imaging for at least 4 weeks prior&#xD;
                  to the first dose of trial treatment and any neurologic symptoms have returned to&#xD;
                  baseline), have no evidence of new or enlarging brain metastases, and are not&#xD;
                  using steroids for at least 7 days prior to trial treatment&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to MK-3475&#xD;
&#xD;
          -  Has an active autoimmune disease requiring systemic treatment within the past 3 months&#xD;
             or a documented history of clinically severe autoimmune disease, or a syndrome that&#xD;
             requires systemic steroids or immunosuppressive agents; patients with vitiligo or&#xD;
             resolved childhood asthma/atopy would be an exception to this rule; patients that&#xD;
             require intermittent use of bronchodilators or local steroid injections would not be&#xD;
             excluded from the study; the use of physiologic doses of corticosteroids may be&#xD;
             approved after consultation with the protocol principal investigator (PI) and Cancer&#xD;
             Immunotherapy Trials Network (CITN); patients with hypothyroidism stable on hormone&#xD;
             replacement or Sjogren's syndrome will not be excluded from the study&#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 patient's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the patient 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;
          -  Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand&#xD;
             (L)1, anti-PD-L2&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, interstitial lung disease or active, non-infectious pneumonitis,&#xD;
             symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or&#xD;
             psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements&#xD;
&#xD;
          -  History of other pulmonary disease such as emphysema or chronic obstructive pulmonary&#xD;
             disease, (forced expiratory volume in one second [FEV1] &lt; 60% of predicted for height&#xD;
             and age); pulmonary function tests (PFTs) are required in patients with prolonged&#xD;
             smoking history or symptoms of respiratory dysfunction&#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-study visit through 120 days&#xD;
             after the last dose of trial treatment; breastfeeding should be discontinued if the&#xD;
             mother is treated with MK-3475&#xD;
&#xD;
               -  Men and non-pregnant, non-breast-feeding women may be enrolled if they are&#xD;
                  willing to use 2 methods of birth control or are considered highly unlikely to&#xD;
                  conceive; highly unlikely to conceive is defined as 1) surgically sterilized, or&#xD;
                  2) postmenopausal (a woman who is &gt;= 45 years of age and has not had menses for&#xD;
                  greater than 1 year will be considered postmenopausal), or 3) not heterosexually&#xD;
                  active for the duration of the study; the two birth control methods can be&#xD;
                  barrier method or a barrier method plus a hormonal method to prevent pregnancy;&#xD;
                  patients should start using birth control from the time of the pre-study visit,&#xD;
                  through the course of the study and for 120 days after the last dose of study&#xD;
                  medication; the following are considered adequate barrier methods of&#xD;
                  contraception: diaphragm, condom (by the partner), copper intrauterine device,&#xD;
                  sponge, or spermicide; appropriate hormonal contraceptives will include any&#xD;
                  registered and marketed contraceptive agent that contains an estrogen and/or a&#xD;
                  progestational agent (including oral, subcutaneous, intrauterine, or&#xD;
                  intramuscular agents)&#xD;
&#xD;
               -  Patients should be informed that taking the study medication may involve unknown&#xD;
                  risks to the fetus (unborn baby) if pregnancy were to occur during the study; in&#xD;
                  order to participate in the study they must adhere to the contraception&#xD;
                  requirement (described above) for the duration of the study and during the&#xD;
                  follow-up period; if there is any question that a patient will not reliably&#xD;
                  comply with the requirements for contraception, that patient should not be&#xD;
                  entered into the study&#xD;
&#xD;
               -  If a patient inadvertently becomes pregnant while on treatment with MK-3475, the&#xD;
                  patient will immediately be removed from the study; the site will contact the&#xD;
                  patient at least monthly and document the patient's status until the pregnancy&#xD;
                  has been completed or terminated; the outcome of the pregnancy will be reported&#xD;
                  without delay and within 24 hours if the outcome is a serious adverse experience&#xD;
                  (e.g., death, abortion, congenital anomaly, or other disabling or&#xD;
                  life-threatening complication to the mother or newborn); the study investigator&#xD;
                  will make every effort to obtain permission to follow the outcome of the&#xD;
                  pregnancy and report the condition of the fetus or newborn; if a male patient&#xD;
                  impregnates his female partner the study personnel at the site must be informed&#xD;
                  immediately and the pregnancy reported and followed&#xD;
&#xD;
          -  Patients who are human immunodeficiency virus (HIV) positive may participate IF they&#xD;
             meet the following eligibility requirements:&#xD;
&#xD;
               -  They must be stable on their anti-retroviral regimen, and they must be healthy&#xD;
                  from an HIV perspective&#xD;
&#xD;
               -  They must have a CD4 count of greater than 250 cells/mcL&#xD;
&#xD;
               -  They must not be receiving prophylactic therapy for an opportunistic infection&#xD;
&#xD;
          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or&#xD;
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is&#xD;
             detected)&#xD;
&#xD;
          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment&#xD;
&#xD;
          -  Has a known human T-lymphotropic virus type 1 (HTLV) infection&#xD;
&#xD;
          -  Patient has a history of (non-infectious) pneumonitis that required steroids or&#xD;
             current pneumonitis&#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>Youn Kim</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Immunotherapy Trials Network</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford Cancer Institute Palo Alto</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University/Sidney Kimmel Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania/Abramson Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2014</study_first_posted>
  <results_first_submitted>January 7, 2019</results_first_submitted>
  <results_first_submitted_qc>January 11, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">February 5, 2019</results_first_posted>
  <last_update_submitted>August 29, 2019</last_update_submitted>
  <last_update_submitted_qc>August 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 20, 2019</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>Mycoses</mesh_term>
    <mesh_term>Mycosis Fungoides</mesh_term>
    <mesh_term>Sezary Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</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>March 8, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT02243579/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Pembrolizumab)</title>
          <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Pembrolizumab)</title>
          <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="24"/>
          </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="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </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="0"/>
                  </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="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome</title>
        <description>A generalized linear model for the objective response rate used a binominal error distribution. The model included as covariates all available baseline predictors of the missing outcomes.</description>
        <time_frame>Up to 3.2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome</title>
          <description>A generalized linear model for the objective response rate used a binominal error distribution. The model included as covariates all available baseline predictors of the missing outcomes.</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="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Confirmed Complete Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Confirmed Partial Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stable Disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Progressive Disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response</title>
        <description>Was estimated using the Kaplan-Meier method (Duration of Response Probability).</description>
        <time_frame>The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard Mycosis Fungoides and Sezary Syndrome response criteria, assessed at 26 and 52 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response</title>
          <description>Was estimated using the Kaplan-Meier method (Duration of Response Probability).</description>
          <units>Duration of Response Probability</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>26 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>52 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8571"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>Was estimated using the Kaplan-Meier method (Progression Free Survival Probability).</description>
        <time_frame>The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed at 26 and 52 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>Was estimated using the Kaplan-Meier method (Progression Free Survival Probability).</description>
          <units>Progression Free Survival Probability</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>26 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7380"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>52 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6457"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Was estimated using the Kaplan-Meier method (Overall Survival Probability).</description>
        <time_frame>The time from randomization to death due to any cause, assessed at 52, 104 and 156 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Was estimated using the Kaplan-Meier method (Overall Survival Probability).</description>
          <units>Overall Survival Probability</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>52 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>104 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7917"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>156 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5429"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Onset of First Drug-related Toxicity</title>
        <description>Summary statistics (mean and SD) for time to onset of first drug-related toxicity was provided.</description>
        <time_frame>Up to 4 years</time_frame>
        <population>Patients with drug-related toxicities included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Onset of First Drug-related Toxicity</title>
          <description>Summary statistics (mean and SD) for time to onset of first drug-related toxicity was provided.</description>
          <population>Patients with drug-related toxicities included in the analysis</population>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.5" spread="121.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Adverse Events Graded Using the Common Terminology Criteria for Adverse Events Version 5.0</title>
        <description>Adverse events were summarized as counts and frequencies by toxicity grade.</description>
        <time_frame>Up to 4 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab)</title>
            <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Events Graded Using the Common Terminology Criteria for Adverse Events Version 5.0</title>
          <description>Adverse events were summarized as counts and frequencies by toxicity grade.</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="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Maximum Toxicity Grade 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Maximum Toxicity Grade 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Maximum Toxicity Grade 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Maximum Toxicity Grade 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 4 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Pembrolizumab)</title>
          <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pembrolizumab: Given IV</description>
        </group>
      </group_list>
      <serious_events>
        <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="7" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Heart Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Corneal Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Periorbital Edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Colonic obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Duodenitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </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="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </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="24"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pneuminitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pulmonary Edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <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="24" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Low Hemoglobin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Keratitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Colonic hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Nausia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Edema trunk</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Weakness (grade decrease)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Firm tender lump on his left lateral thigh, no trauma to the area</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Generalized edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Inflammation/Flare reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Esophageal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Infection S/P scheduled Mohs surgery</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Right lower leg infection related to approved radiation and wound care</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Mucosal infection (thrush)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Mucosal infection - thrush</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Upper eyelid infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>otitis externa</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>rash pustular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase inceased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Cardiac troponin T increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Investigations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>white blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </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="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Herniated disc</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>neck pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>BCC right leg</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>SCC forehead</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Horseness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Postnasal drip</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Bilateral pulmonary infiltrates</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Sinus inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Erythroderma</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Skin eruption/flare, rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>immune mediated flare reaction on the face</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>pustular rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Mild skin peeling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Erythroderma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Skin flare</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Excess skin peeling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Scheduled Mohs surgery</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Asa Davis</name_or_title>
      <organization>Fred Hutchinson Cancer Research Center</organization>
      <phone>206-667-5300</phone>
      <email>akdavis@fredhutch.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02243579
org study id: NCI-2014-00709
secondary id: NCI-2014-00709
secondary id: CITN-10
secondary id: CITN-10
secondary id: P30CA015704
secondary id: U01CA154967
nct id: NCT02243579
lead sponsor: 
has dmc: No
This phase II trial studies how well pembrolizumab works in treating patients with stage
      IB-IVB mycosis fungoides or Sezary syndrome that has returned after a period of improvement
      or has not responded to at least one type of treatment. Monoclonal antibodies, such as
      pembrolizumab, may block cancer growth in different ways by targeting certain cells.
PRIMARY OBJECTIVES:

      I. To assess the response rate of MK-3475 (pembrolizumab) in subjects with
      relapsed/refractory mycosis fungoides/Sezary syndrome (MF/SS).

      SECONDARY OBJECTIVES:

      I. To explore the clinical activity of MK-3475 in subjects with relapsed/refractory MF and SS
      with respect to the following endpoints: duration of response (DOR); progression-free
      survival (PFS); overall survival (OS).

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat
      every 3 weeks for up to 2 years (6 months for patients achieving complete response [CR]) in
      the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 30 days and then every 12
      weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome
time frame: Up to 3.2 years
description: A generalized linear model for the objective response rate used a binominal error distribution. The model included as covariates all available baseline predictors of the missing outcomes.
measure: Duration of Response
time frame: The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard Mycosis Fungoides and Sezary Syndrome response criteria, assessed at 26 and 52 weeks
description: Was estimated using the Kaplan-Meier method (Duration of Response Probability).
measure: Progression Free Survival (PFS)
time frame: The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed at 26 and 52 weeks
description: Was estimated using the Kaplan-Meier method (Progression Free Survival Probability).
measure: Overall Survival (OS)
time frame: The time from randomization to death due to any cause, assessed at 52, 104 and 156 weeks
description: Was estimated using the Kaplan-Meier method (Overall Survival Probability).
measure: Time to Onset of First Drug-related Toxicity
time frame: Up to 4 years
description: Summary statistics (mean and SD) for time to onset of first drug-related toxicity was provided.
measure: Incidence of Adverse Events Graded Using the Common Terminology Criteria for Adverse Events Version 5.0
time frame: Up to 4 years
description: Adverse events were summarized as counts and frequencies by toxicity grade.
arm group label: Treatment (pembrolizumab)
arm group type: Experimental
description: Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (pembrolizumab)
intervention type: Biological
intervention name: Pembrolizumab
description: Given IV
arm group label: Treatment (pembrolizumab)
other name: Keytruda
other name: Lambrolizumab
other name: MK-3475
other name: SCH 900475
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Youn Kim
role: Principal Investigator
affiliation: Cancer Immunotherapy Trials Network
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Mycoses
mesh term: Mycosis Fungoides
mesh term: Sezary Syndrome
mesh term: Syndrome
mesh term: Pembrolizumab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 