<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/NCT03011814</url>
  </required_header>
  <id_info>
    <org_study_id>16221</org_study_id>
    <secondary_id>NCI-2016-02061</secondary_id>
    <secondary_id>16221</secondary_id>
    <secondary_id>R01CA229510</secondary_id>
    <nct_id>NCT03011814</nct_id>
  </id_info>
  <brief_title>Durvalumab With or Without Lenalidomide in Treating Patients With Relapsed or Refractory Cutaneous or Peripheral T Cell Lymphoma</brief_title>
  <official_title>A Phase 1/2 Trial of Durvalumab (MEDI4736) When Given as a Single Agent or in Combination With Lenalidomide in Patients With Relapsed/ Refractory Peripheral T-cell Lymphoma, Including Cutaneous T-cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>City of Hope Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>City of Hope Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase I/II trial studies the best dose and side effects of durvalumab and to&#xD;
      see how well it works with or without lenalidomide in treating patients with cutaneous or&#xD;
      peripheral T cell lymphoma that has come back and does not respond to treatment. Monoclonal&#xD;
      antibodies, such as durvalumab, may interfere with the ability of cancer cells to grow and&#xD;
      spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the&#xD;
      growth of cancer cells, either by killing the cells, by stopping them from dividing, or by&#xD;
      stopping them from spreading. Giving durvalumab and lenalidomide may work better in treating&#xD;
      patients with cutaneous or peripheral T cell lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the maximum tolerated dose (recommended phase 2 dose, RP2D) of lenalidomide,&#xD;
      when given in combination with fixed-dose durvalumab. (Phase 1) II. To assess the safety and&#xD;
      tolerability of the lenalidomide/durvalumab regimen, and accompanying dose modification plan,&#xD;
      by evaluation of toxicities including: type, frequency, severity, attribution, time course&#xD;
      and duration. (Phase 1) III. To evaluate the anti-tumor activity durvalumab (MEDI4736) as&#xD;
      single agent therapy and as part of combination therapy (+lenalidomide); activity assessed by&#xD;
      overall response rate (ORR). (Phase 2)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate and assess response duration and survival probabilities (overall and&#xD;
      event-free). (Phase 2) II. To summarize and assess toxicities by type, frequency, severity,&#xD;
      attribution, time course and duration. (Phase 2) III. To assess clinically meaningful&#xD;
      reduction in pruritus (CMRP) in patients with CTCL (critical quality of life measure). (Phase&#xD;
      2)&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To identify the malignant CD4+ T cells within the skin microenvironment. II. To&#xD;
      characterize the spatial and functional relationship of malignant T cells with other immune&#xD;
      cells, their expression of key immune checkpoints and correlate with response.&#xD;
&#xD;
      III. To identify aberrantly expressed micro(mi) ribonucleic acid (RNA)s involved in cutaneous&#xD;
      T-cell lymphoma (CTCL) and messenger (m)RNAs that may predict response and/or&#xD;
      treatment-related toxicity.&#xD;
&#xD;
      IV. To evaluate whether or not the identified miRNAs are involved in regulating key immune&#xD;
      checkpoints.&#xD;
&#xD;
      OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II&#xD;
      study. Patients are randomized to 1 of 2 arms,&#xD;
&#xD;
      ARM I: Patients receive durvalumab intravenously (IV) over 1 hour on day 1. Treatment repeats&#xD;
      every 28 days (+/- 3) for up to 13 courses in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      ARM II: Patients receive durvalumab IV over 1 hour on day 1 and lenalidomide orally (PO) once&#xD;
      daily (QD) on days 1-21. Treatment repeats every 28 (+/- 3) days for up to 13 courses in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for up to 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 8, 2017</start_date>
  <completion_date type="Anticipated">June 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2025</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>CTCL specific response assessed by Lugano Classification</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>CTCL response will be used to establish global response, which incorporates nodal, visceral and cutaneous lesions/disease. mSWAT tool will be used for documenting responses in skin of patients with CTCL. PTCL specific response assessment criteria per Lugano Classification will be used.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose limiting toxicity assessed by CTCAE version 4.03</measure>
    <time_frame>Up to 84 days</time_frame>
    <description>Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of complete response</measure>
    <time_frame>Date when criteria for CR first met until time of loss of CR (relapse/recurrence) or death (as a result of MF/SS or acute toxicity of treatment), assessed up to 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>From date of first dose of study drug to first documented disease relapse, progression or death from any cause, whichever occurs first, assessed up to 12 months</time_frame>
    <description>Will be estimated using the product-limit method of Kaplan and Meier.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of adverse events assessed by National Cancer Institute CTCAE version 4.03</measure>
    <time_frame>Up to 90 days post-treatment</time_frame>
    <description>Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ORR defined as proportion of patients with complete response (CR) and partial response (PR)</measure>
    <time_frame>Up to 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of first dose of study drug to date of death from any cause, assessed up to 12 months</time_frame>
    <description>Will be estimated using the product-limit method of Kaplan and Meier.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Date of initiation of treatment to first date meets criteria for progressive disease or death as a result of any cause, assessed up to 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Response duration</measure>
    <time_frame>From the date of first documented response to the date of first documented disease relapse, progression or death whichever occurs first, assessed up to 12 months</time_frame>
    <description>95% Clopper Pearson binomial confidence interval will be calculated. Response rates will also be explored based on number/type of prior therapies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to response</measure>
    <time_frame>Date of initiation of treatment to date when criteria for response (PR or CR) first met, assessed up to 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pruritus assessment</measure>
    <time_frame>Baseline up to 12 months</time_frame>
    <description>Changes in pruritus VAS score will be assessed using descriptive statistics.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in biomarkers</measure>
    <time_frame>Baseline up to 12 months</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">62</enrollment>
  <condition>Folliculotropic Mycosis Fungoides</condition>
  <condition>Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Recurrent Mycosis Fungoides</condition>
  <condition>Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Mycosis Fungoides</condition>
  <condition>Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified</condition>
  <condition>Sezary Syndrome</condition>
  <condition>Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Arm I (durvalumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive durvalumab IV over 1 hour on day 1. Treatment repeats every 28 (+/- 3) days for up to 13 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (durvalumab, lenalidomide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive durvalumab IV over 1 hour on day 1 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 (+/- 3) days for up to 13 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (durvalumab)</arm_group_label>
    <arm_group_label>Arm II (durvalumab, lenalidomide)</arm_group_label>
    <other_name>Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer</other_name>
    <other_name>MEDI-4736</other_name>
    <other_name>MEDI4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (durvalumab)</arm_group_label>
    <arm_group_label>Arm II (durvalumab, lenalidomide)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm II (durvalumab, lenalidomide)</arm_group_label>
    <other_name>CC-5013</other_name>
    <other_name>CC5013</other_name>
    <other_name>CDC 501</other_name>
    <other_name>Revlimid</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented informed consent of the participant and/or legally authorized&#xD;
             representative&#xD;
&#xD;
          -  Registered into Revlimid REMS program&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2&#xD;
&#xD;
          -  Fully recovered from acute toxicities (except alopecia) of all prior therapies to&#xD;
             Common Terminology Criteria for Adverse Events (CTCAE) =&lt; grade 1&#xD;
&#xD;
          -  Relapsed/refractory disease&#xD;
&#xD;
          -  Failed &gt;= 2 prior systemic therapies *NOTE: For systemic ALCL prior systemic therapy&#xD;
             must also include progression on brentuximab vedotin&#xD;
&#xD;
        CUTANEOUS T-CELL LYMPHOMA (CTCL) ONLY&#xD;
&#xD;
          -  Histologically confirmed mycosis fungoides (MF) or Sezary syndrome (SS); Phase 1: &gt;=&#xD;
             stage IIB OR &gt;= stage IB-IIA folliculotropic/transformed MF; Phase 2: &gt;= stage IB&#xD;
&#xD;
               -  Stage of disease according to TNMB classification&#xD;
&#xD;
               -  Pathology report must be diagnostic or be consistent with MF/SS criteria&#xD;
&#xD;
               -  SS is defined as meeting T4 plus B2 criteria; where the biopsy of erythrodermic&#xD;
                  skin may only reveal suggestive but not diagnostic histopathological features,&#xD;
                  the diagnosis may be based on either node biopsy or fulfillment of B2 criteria&#xD;
&#xD;
               -  For MF where the histological diagnosis by light microscopic examination is not&#xD;
                  confirmed, diagnostic criteria that has been recommended by the International&#xD;
                  Society of Cutaneous Lymphomas (ISCL) should be used&#xD;
&#xD;
          -  Measurable disease per modified severity weighted assessment tool (mSWAT) and/or&#xD;
             Sezary count&#xD;
&#xD;
          -  Baseline skin biopsy taken within 6 months available for central review submission&#xD;
&#xD;
        PERIPHERAL T-CELL LYMPHOMA (PTCL) ONLY&#xD;
&#xD;
          -  Histologically confirmed PTCL as defined by World Health Organization (WHO) 2008&#xD;
             criteria&#xD;
&#xD;
          -  Measurable and/or evaluable disease per Lugano Classification&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000/mm^3&#xD;
&#xD;
             * Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is&#xD;
             secondary to disease involvement&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mm^3&#xD;
&#xD;
             * Platelet transfusions are not permitted within 14 days of platelet assessment unless&#xD;
             cytopenia is secondary to disease involvement&#xD;
&#xD;
          -  Total serum bilirubin =&lt; 2.2 mg/dL&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) =&lt; 2 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) =&lt; 2 x ULN&#xD;
&#xD;
          -  Creatinine clearance of &gt;= 60 mL/min per the Cockcroft-Gault formula&#xD;
&#xD;
          -  If not receiving anticoagulants: international normalized ratio (INR) AND prothrombin&#xD;
             (PT) =&lt; 1.5 x ULN&#xD;
&#xD;
             * If on anticoagulant therapy: PT must be within therapeutic range of intended used of&#xD;
             anticoagulants&#xD;
&#xD;
          -  Female of childbearing potential: negative urine or serum pregnancy test&#xD;
&#xD;
             * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy&#xD;
             test will be required&#xD;
&#xD;
          -  Female of child bearing potential: willing to use 2 methods of birth control or be&#xD;
             surgically sterile, or abstain from heterosexual activity for the course of the study&#xD;
             through 90 days after the last dose of study medication&#xD;
&#xD;
             * Childbearing potential defined as not being surgically sterilized or have not been&#xD;
             free from menses for &gt; 1 year&#xD;
&#xD;
          -  Male: use an adequate method of contraception starting with the first dose of study&#xD;
             therapy through 90 days after the last dose of study therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Immunotherapy with immune checkpoint inhibitors, cell-based therapies, or cancer&#xD;
             vaccines&#xD;
&#xD;
          -  Lenalidomide, thalidomide or other immunomodulatory drugs (IMiDs)&#xD;
&#xD;
          -  Monoclonal antibody within 5 half-lives of the antibody prior to initiating protocol&#xD;
             therapy&#xD;
&#xD;
          -  Any systemic therapy, including monoclonal antibody within 28 days or 5 half-lives&#xD;
             (whichever is shorter) of initiating protocol therapy&#xD;
&#xD;
          -  Any skin-directed therapy within 14 days prior to initiating protocol therapy&#xD;
&#xD;
          -  Any radiation therapy within 21 days prior to initiating protocol therapy&#xD;
&#xD;
          -  Immunosuppressive medication within 14 days prior to the first dose of study&#xD;
             treatment; the following are exceptions to this criterion:&#xD;
&#xD;
               -  Intranasal, inhaled, topical or local steroid injections (e.g., intra-articular&#xD;
                  injection) and are on stable dose for at least 28 days&#xD;
&#xD;
               -  Systemic corticosteroids at physiologic doses of &lt; 10 mg/day of prednisone or&#xD;
                  equivalent&#xD;
&#xD;
          -  Live, attenuated vaccine within 30 days prior to the first dose of protocol therapy&#xD;
&#xD;
          -  History of pneumonitis (non-infectious) that required steroids or current pneumonitis&#xD;
&#xD;
          -  Disease free of prior malignancies for &gt;= 5 years with the exception of:&#xD;
&#xD;
               -  Currently treated squamous cell and basal cell carcinoma of the skin&#xD;
&#xD;
               -  Carcinoma in situ of the cervix, or&#xD;
&#xD;
               -  Surgically removed melanoma in situ of the skin (stage 0) with histological&#xD;
                  confirmed free margins of excision or&#xD;
&#xD;
               -  Prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical&#xD;
                  staging system) that has/have been surgically cured, or&#xD;
&#xD;
               -  Any other malignancy that has/have been curatively treated with surgery and/or&#xD;
                  localized radiation&#xD;
&#xD;
          -  Allergic reaction/ hypersensitivity to thalidomide or to the excipients contained in&#xD;
             the formulation of durvalumab&#xD;
&#xD;
          -  Female only: pregnant or lactating&#xD;
&#xD;
          -  Prior stem cell transplantation&#xD;
&#xD;
          -  Acute infection requiring systemic treatment&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Active hepatitis B or C infection&#xD;
&#xD;
          -  Conditions requiring chronic steroid or immunosuppressive treatment that likely need&#xD;
             additional steroid or immunosuppressive treatments in addition to the protocol therapy&#xD;
&#xD;
          -  Current peripheral neuropathy &gt;= grade 2&#xD;
&#xD;
          -  Renal failure requiring hemodialysis or peritoneal dialysis&#xD;
&#xD;
          -  Unstable cardiac disease as defined by one of the following:&#xD;
&#xD;
               -  Cardiac events such as myocardial infarction (MI) within the past 6 months&#xD;
&#xD;
               -  NYHA (New York Heart Association) heart failure class III-IV&#xD;
&#xD;
               -  Uncontrolled atrial fibrillation or hypertension&#xD;
&#xD;
          -  Major surgery (as defined by the investigator) within the 28 days prior to the first&#xD;
             dose of study treatment&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders requiring therapy&#xD;
             within the past 3 years prior to the start of treatment; the following are exceptions&#xD;
             to this criterion:&#xD;
&#xD;
               -  Vitiligo or alopecia;&#xD;
&#xD;
               -  Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone&#xD;
                  replacement; or&#xD;
&#xD;
               -  Psoriasis not requiring systemic treatment&#xD;
&#xD;
          -  History of primary immunodeficiency&#xD;
&#xD;
          -  Incidence of gastrointestinal disease that may significantly alter the absorption of&#xD;
             lenalidomide&#xD;
&#xD;
          -  Any other condition that would, in the investigator's judgement, contraindicate the&#xD;
             patient's participation in the clinical study due to safety concerns or compliance&#xD;
             with clinical study procedures, e.g., infection/inflammation, intestinal obstruction,&#xD;
             unable to swallow medication, social/psychological issues, etc&#xD;
&#xD;
          -  In the opinion of the investigator, may not be able to comply with all study&#xD;
             procedures (including compliance issues related to feasibility/logistics)&#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>Christiane Querfeld, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>City of Hope Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christiane Querfeld, MD</last_name>
      <phone>626-256-4673</phone>
      <email>cquerfeld@coh.org</email>
    </contact>
    <investigator>
      <last_name>Christiane Querfeld, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </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>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Steven M. Horwitz, MD</last_name>
      <phone>212-639-3045</phone>
      <email>horwitzs@mskcc.org</email>
    </contact>
    <investigator>
      <last_name>Steven M. Horwitz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Pierluigi Porcu, MD</last_name>
      <phone>215-955-8874</phone>
      <email>Pierluigi.Porcu@jefferson.edu</email>
    </contact>
    <investigator>
      <last_name>Pierluigi Porcu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Michelle A. Fanale, MD</last_name>
      <phone>713-792-2860</phone>
      <email>mfanale@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>Michelle A. Fanale, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>January 12, 2023</last_update_submitted>
  <last_update_submitted_qc>January 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2023</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>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
    <mesh_term>Mycosis Fungoides</mesh_term>
    <mesh_term>Sezary Syndrome</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Cutaneous</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Immunoglobulin G</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03011814
org study id: 16221
secondary id: NCI-2016-02061
secondary id: 16221
secondary id: R01CA229510
nct id: NCT03011814
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This randomized phase I/II trial studies the best dose and side effects of durvalumab and to
      see how well it works with or without lenalidomide in treating patients with cutaneous or
      peripheral T cell lymphoma that has come back and does not respond to treatment. Monoclonal
      antibodies, such as durvalumab, may interfere with the ability of cancer cells to grow and
      spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the
      growth of cancer cells, either by killing the cells, by stopping them from dividing, or by
      stopping them from spreading. Giving durvalumab and lenalidomide may work better in treating
      patients with cutaneous or peripheral T cell lymphoma.
PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (recommended phase 2 dose, RP2D) of lenalidomide,
      when given in combination with fixed-dose durvalumab. (Phase 1) II. To assess the safety and
      tolerability of the lenalidomide/durvalumab regimen, and accompanying dose modification plan,
      by evaluation of toxicities including: type, frequency, severity, attribution, time course
      and duration. (Phase 1) III. To evaluate the anti-tumor activity durvalumab (MEDI4736) as
      single agent therapy and as part of combination therapy (+lenalidomide); activity assessed by
      overall response rate (ORR). (Phase 2)

      SECONDARY OBJECTIVES:

      I. To estimate and assess response duration and survival probabilities (overall and
      event-free). (Phase 2) II. To summarize and assess toxicities by type, frequency, severity,
      attribution, time course and duration. (Phase 2) III. To assess clinically meaningful
      reduction in pruritus (CMRP) in patients with CTCL (critical quality of life measure). (Phase
      2)

      TERTIARY OBJECTIVES:

      I. To identify the malignant CD4+ T cells within the skin microenvironment. II. To
      characterize the spatial and functional relationship of malignant T cells with other immune
      cells, their expression of key immune checkpoints and correlate with response.

      III. To identify aberrantly expressed micro(mi) ribonucleic acid (RNA)s involved in cutaneous
      T-cell lymphoma (CTCL) and messenger (m)RNAs that may predict response and/or
      treatment-related toxicity.

      IV. To evaluate whether or not the identified miRNAs are involved in regulating key immune
      checkpoints.

      OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II
      study. Patients are randomized to 1 of 2 arms,

      ARM I: Patients receive durvalumab intravenously (IV) over 1 hour on day 1. Treatment repeats
      every 28 days (+/- 3) for up to 13 courses in the absence of disease progression or
      unacceptable toxicity.

      ARM II: Patients receive durvalumab IV over 1 hour on day 1 and lenalidomide orally (PO) once
      daily (QD) on days 1-21. Treatment repeats every 28 (+/- 3) days for up to 13 courses in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for up to 12 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: CTCL specific response assessed by Lugano Classification
time frame: Up to 12 months
description: CTCL response will be used to establish global response, which incorporates nodal, visceral and cutaneous lesions/disease. mSWAT tool will be used for documenting responses in skin of patients with CTCL. PTCL specific response assessment criteria per Lugano Classification will be used.
measure: Dose limiting toxicity assessed by CTCAE version 4.03
time frame: Up to 84 days
description: Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
measure: Duration of complete response
time frame: Date when criteria for CR first met until time of loss of CR (relapse/recurrence) or death (as a result of MF/SS or acute toxicity of treatment), assessed up to 12 months
measure: Event-free survival
time frame: From date of first dose of study drug to first documented disease relapse, progression or death from any cause, whichever occurs first, assessed up to 12 months
description: Will be estimated using the product-limit method of Kaplan and Meier.
measure: Incidence of adverse events assessed by National Cancer Institute CTCAE version 4.03
time frame: Up to 90 days post-treatment
description: Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
measure: ORR defined as proportion of patients with complete response (CR) and partial response (PR)
time frame: Up to 12 months
measure: Overall survival
time frame: From date of first dose of study drug to date of death from any cause, assessed up to 12 months
description: Will be estimated using the product-limit method of Kaplan and Meier.
measure: Progression free survival
time frame: Date of initiation of treatment to first date meets criteria for progressive disease or death as a result of any cause, assessed up to 12 months
measure: Response duration
time frame: From the date of first documented response to the date of first documented disease relapse, progression or death whichever occurs first, assessed up to 12 months
description: 95% Clopper Pearson binomial confidence interval will be calculated. Response rates will also be explored based on number/type of prior therapies.
measure: Time to response
time frame: Date of initiation of treatment to date when criteria for response (PR or CR) first met, assessed up to 12 months
measure: Pruritus assessment
time frame: Baseline up to 12 months
description: Changes in pruritus VAS score will be assessed using descriptive statistics.
measure: Changes in biomarkers
time frame: Baseline up to 12 months
arm group label: Arm I (durvalumab)
arm group type: Experimental
description: Patients receive durvalumab IV over 1 hour on day 1. Treatment repeats every 28 (+/- 3) days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II (durvalumab, lenalidomide)
arm group type: Experimental
description: Patients receive durvalumab IV over 1 hour on day 1 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 (+/- 3) days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Durvalumab
description: Given IV
arm group label: Arm I (durvalumab)
arm group label: Arm II (durvalumab, lenalidomide)
other name: Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
other name: MEDI-4736
other name: MEDI4736
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (durvalumab)
arm group label: Arm II (durvalumab, lenalidomide)
intervention type: Drug
intervention name: Lenalidomide
description: Given PO
arm group label: Arm II (durvalumab, lenalidomide)
other name: CC-5013
other name: CC5013
other name: CDC 501
other name: Revlimid
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christiane Querfeld, MD
role: Principal Investigator
affiliation: City of Hope Medical Center
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Mycoses
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Mycosis Fungoides
mesh term: Sezary Syndrome
mesh term: Lymphoma, T-Cell, Cutaneous
mesh term: Recurrence
mesh term: Lenalidomide
mesh term: Durvalumab
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Immunoglobulin G