<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/NCT03776864</url>
  </required_header>
  <id_info>
    <org_study_id>RG1003718</org_study_id>
    <secondary_id>NCI-2018-02836</secondary_id>
    <secondary_id>10075</secondary_id>
    <nct_id>NCT03776864</nct_id>
  </id_info>
  <brief_title>Umbralisib and Pembrolizumab in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma</brief_title>
  <official_title>A Phase II Trial of Umbralisib and Pembrolizumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>TG Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</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 phase II trial studies how well umbralisib and pembrolizumab work in treating patients&#xD;
      with classical Hodgkin lymphoma that has come back (relapsed) or does not respond to&#xD;
      treatment (refractory). Umbralisib may stop the growth of cancer cells by blocking some of&#xD;
      the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as&#xD;
      pembrolizumab, may help the body's immune system attack the cancer, and may interfere with&#xD;
      the ability of cancer cells to grow and spread. Giving umbralisib and pembrolizumab may work&#xD;
      better in treating classical Hodgkin lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE:&#xD;
&#xD;
      Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in&#xD;
      the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib&#xD;
      orally (PO) daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 28 days, then up to 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Company providing drug terminated their oncology program&#xD;
  </why_stopped>
  <start_date type="Actual">September 26, 2019</start_date>
  <completion_date type="Actual">September 14, 2021</completion_date>
  <primary_completion_date type="Actual">September 14, 2021</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>Complete Response Rate</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve a complete response (CR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve an overall response (OR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass; Partial Metabolic Response, Deauville score of 4 or 5 with reduced uptake compared to baseline and residual mass(es) of any size; No Response or Stable Disease, Deauville score of 4 or 5 with no significant change in FDG uptake from baseline at interim or end of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>Up to 28 days post-treatment, approximately 2 years</time_frame>
    <description>Measured via CTCAE v4.0. Incidence of adverse events is defined as the count of participants who experienced an adverse event.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Hodgkin's Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (pembrolizumab, umbralisib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pembrolizumab, umbralisib)</arm_group_label>
    <other_name>Immunoglobulin G4</other_name>
    <other_name>Anti-(Human Programmed Cell Death 1)</other_name>
    <other_name>Lambrolizumab</other_name>
    <other_name>MK-3475</other_name>
    <other_name>SCH 900475</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Umbralisib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (pembrolizumab, umbralisib)</arm_group_label>
    <other_name>TGR-1202</other_name>
    <other_name>RP5264</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Relapsed or refractory CHL that has received at least 1 prior lines of therapy&#xD;
&#xD;
          -  Measurable fludeoxyglucose F-18 (FDG)-avid disease defined by standard criteria&#xD;
             (Lugano 2014) and a minimum of 1.0 cm in diameter&#xD;
&#xD;
          -  Prior treatment with anti-PD1 or anti-PDL1 therapy is allowed.&#xD;
&#xD;
             * Patients who are currently on anti-PD1 or anti-PDL1 therapy who have failed to&#xD;
             achieve a CR after at least 18 weeks of treatment may enroll on study. For these&#xD;
             patients, anti-PD1 or anti-PDL1 therapy may be delayed for screening and to align&#xD;
             pembrolizumab dosing with the expected cycle 1 day 1. Patients with progressive&#xD;
             disease after prior anti-PD1 or anti-PDL1 therapy do not have to be treated for 18&#xD;
             weeks&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2&#xD;
&#xD;
          -  Ability to swallow and retain oral medication&#xD;
&#xD;
          -  Willingness and ability to comply with study and follow-up procedures, and give&#xD;
             written informed consent&#xD;
&#xD;
          -  Female subjects of childbearing potential must be surgically sterile, be&#xD;
             post-menopausal (for at least 1 year prior to screening visit), or must have a&#xD;
             negative pregnancy test within 3 days prior to cycle 1 day 1 and agree to use&#xD;
             medically acceptable contraception throughout the study period and for 4 months after&#xD;
             the last dose of either study drug. Men of reproductive potential may not participate&#xD;
             unless they agree to use medically acceptable contraception throughout the study&#xD;
             period and for 4 months after the last dose of either study drug&#xD;
&#xD;
          -  Patients must be expected to receive at least 2 cycles of therapy&#xD;
&#xD;
          -  Patients should have a life expectancy if untreated of &gt;= 90 days in the opinion of&#xD;
             the investigator&#xD;
&#xD;
          -  Patients must have a FDG-positron emission tomography (PET)-computed tomography (CT)&#xD;
             of chest, abdomen, and pelvis within 42 days of enrollment&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt; 750&#xD;
&#xD;
          -  Platelet count &gt; 40,000&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 times the upper limit of normal (ULN)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 2.5 x ULN (if&#xD;
             known liver involvement then =&lt; 5 x ULN is allowed)&#xD;
&#xD;
          -  Calculated creatinine clearance &gt; 30 mL/min (as calculated by the Cockcroft-Gault&#xD;
             formula)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving cancer therapy (i.e., chemotherapy, immunotherapy, biologic&#xD;
             therapy, hormonal therapy, surgery and/or tumor embolization, prednisone &gt; 10 mg or&#xD;
             equivalent) or any investigational drug within 21 days of cycle 1 day 1. Patients&#xD;
             receiving radiation therapy within 14 days from cycle 1 day 1. Anti-PD1 or anti-PDL1&#xD;
             therapy in patients with less than a CR after 18 weeks of such therapy is permitted to&#xD;
             continue on schedule&#xD;
&#xD;
          -  Discontinuation from prior anti-PD1 or anti-PDL1 therapy due to immune-related adverse&#xD;
             event or any other treatment-related adverse event&#xD;
&#xD;
          -  Autologous transplantation within 100 days&#xD;
&#xD;
          -  Prior allogeneic transplant within 12 months of initiation on study&#xD;
&#xD;
          -  Active graft versus host disease (GVHD) within 90 days prior to cycle 1 day 1&#xD;
&#xD;
          -  Evidence of active central nervous system lymphoma&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Evidence of chronic active hepatitis B or chronic active hepatitis C infection&#xD;
             (hepatitis C virus [HCV]), active cytomegalovirus (CMV), or known history of human&#xD;
             immunodeficiency virus (HIV). If hepatitis B core (HBc) antibody, HCV antibody or CMV&#xD;
             immunoglobulin (Ig)M is positive, the patient should be correspondingly evaluated for&#xD;
             the presence of HBV, HCV or CMV by deoxyribonucleic acid (DNA) (polymerase chain&#xD;
             reaction [PCR]) to determine presence or absence of active infection. If HBc antibody&#xD;
             is positive, the subject must be evaluated for the presence of hepatitis B virus (HBV)&#xD;
             DNA by polymerase chain reaction (PCR). If HCV antibody is positive, the subject must&#xD;
             be evaluated for the presence of HCV ribonucleic acid (RNA) by PCR. Subjects with&#xD;
             positive HBc antibody and negative HBV DNA by PCR are eligible. Subjects with positive&#xD;
             HCV antibody and negative HCV RNA by PCR are eligible. Subjects who are&#xD;
             cytomegalovirus (CMV) IgG or CMV IgM positive but who are CMV DNA negative by PCR are&#xD;
             eligible&#xD;
&#xD;
          -  Prior exposure to idelalisib (CAL-101), duvelisib (IPI-145), or any drug that&#xD;
             specifically inhibits phosphoinositide-3-kinase (PI3K)&#xD;
&#xD;
          -  Evidence of ongoing active systemic bacterial, fungal or viral infection&#xD;
&#xD;
          -  Any severe and/or uncontrolled medical conditions or other conditions that could&#xD;
             affect their participation in the study such as:&#xD;
&#xD;
               -  Symptomatic, or history of documented congestive heart failure (New York [NY]&#xD;
                  Heart Association functional classification III-IV)&#xD;
&#xD;
               -  Significant cardiovascular disease such as uncontrolled or symptomatic&#xD;
                  arrhythmias, congestive heart failure, or myocardial infarction within 6 months&#xD;
                  of randomization&#xD;
&#xD;
               -  Concomitant use of medication known to cause QT prolongation or torsades de&#xD;
                  pointes. Poorly controlled or clinically significant atherosclerotic vascular&#xD;
                  disease including cerebrovascular accident (CVA), transient ischemic attack&#xD;
                  (TIA), angioplasty, cardiac/vascular stenting within 3 months of randomization&#xD;
&#xD;
          -  Patients with other prior malignancies except for adequately treated basal cell&#xD;
             carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or&#xD;
             other cancer from which the patient has been disease-free for 5 years or greater,&#xD;
             unless approved by the protocol principal investigator&#xD;
&#xD;
          -  Patients with an active autoimmune disorder (with the exception of autoimmune&#xD;
             hemolytic anemia, idiopathic thrombocytopenic purpura [ITP] or vitiligo)&#xD;
&#xD;
          -  History of non-infectious pneumonitis related to prior line of therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ryan Lynch</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</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>April 2023</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <results_first_submitted>January 28, 2023</results_first_submitted>
  <results_first_submitted_qc>April 27, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 3, 2023</results_first_posted>
  <disposition_first_submitted>July 22, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>April 27, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">May 3, 2023</disposition_first_posted>
  <last_update_submitted>April 27, 2023</last_update_submitted>
  <last_update_submitted_qc>April 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>Ryan Lynch</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Hodgkin Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Immunoglobulin G</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>October 29, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT03776864/Prot_SAP_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 28, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT03776864/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Pembrolizumab, Umbralisib)</title>
          <description>Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
Pembrolizumab: Given IV&#xD;
Umbralisib: Given PO</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Pembrolizumab, Umbralisib)</title>
          <description>Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
Pembrolizumab: Given IV&#xD;
Umbralisib: Given PO</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46" lower_limit="30" upper_limit="74"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="1"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </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="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Complete Response Rate</title>
        <description>Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve a complete response (CR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass.</description>
        <time_frame>Up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Umbralisib)</title>
            <description>Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
Pembrolizumab: Given IV&#xD;
Umbralisib: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Complete Response Rate</title>
          <description>Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve a complete response (CR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass.</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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate</title>
        <description>Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve an overall response (OR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass; Partial Metabolic Response, Deauville score of 4 or 5 with reduced uptake compared to baseline and residual mass(es) of any size; No Response or Stable Disease, Deauville score of 4 or 5 with no significant change in FDG uptake from baseline at interim or end of treatment.</description>
        <time_frame>Up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Umbralisib)</title>
            <description>Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
Pembrolizumab: Given IV&#xD;
Umbralisib: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate</title>
          <description>Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve an overall response (OR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass; Partial Metabolic Response, Deauville score of 4 or 5 with reduced uptake compared to baseline and residual mass(es) of any size; No Response or Stable Disease, Deauville score of 4 or 5 with no significant change in FDG uptake from baseline at interim or end of treatment.</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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Measured via CTCAE v4.0. Incidence of adverse events is defined as the count of participants who experienced an adverse event.</description>
        <time_frame>Up to 28 days post-treatment, approximately 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Pembrolizumab, Umbralisib)</title>
            <description>Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
Pembrolizumab: Given IV&#xD;
Umbralisib: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Measured via CTCAE v4.0. Incidence of adverse events is defined as the count of participants who experienced an adverse event.</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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse were collected from the time of informed consent through 28 days after last dose of study drug. Adverse events were collected for 2 years.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Pembrolizumab, Umbralisib)</title>
          <description>Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
Pembrolizumab: Given IV&#xD;
Umbralisib: Given PO</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <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="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bitter taste in mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Palate lesion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Allergies</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bilateral axilla pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain in extremities</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cramping in legs</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lower back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Soreness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lightheadedness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Peripheral neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Frequent urination</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Difficulty urinating</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Perceived distal vascular insufficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Ryan Lynch</name_or_title>
      <organization>University of Washington</organization>
      <phone>206-606-1739</phone>
      <email>rclynch@uw.edu</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/NCT03776864
org study id: RG1003718
secondary id: NCI-2018-02836
secondary id: 10075
nct id: NCT03776864
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well umbralisib and pembrolizumab work in treating patients
      with classical Hodgkin lymphoma that has come back (relapsed) or does not respond to
      treatment (refractory). Umbralisib may stop the growth of cancer cells by blocking some of
      the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as
      pembrolizumab, may help the body's immune system attack the cancer, and may interfere with
      the ability of cancer cells to grow and spread. Giving umbralisib and pembrolizumab may work
      better in treating classical Hodgkin lymphoma.
OUTLINE:

      Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in
      the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib
      orally (PO) daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 28 days, then up to 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete Response Rate
time frame: Up to 1 year
description: Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve a complete response (CR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass.
measure: Overall Response Rate
time frame: Up to 1 year
description: Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve an overall response (OR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass; Partial Metabolic Response, Deauville score of 4 or 5 with reduced uptake compared to baseline and residual mass(es) of any size; No Response or Stable Disease, Deauville score of 4 or 5 with no significant change in FDG uptake from baseline at interim or end of treatment.
measure: Number of Participants With Adverse Events
time frame: Up to 28 days post-treatment, approximately 2 years
description: Measured via CTCAE v4.0. Incidence of adverse events is defined as the count of participants who experienced an adverse event.
arm group label: Treatment (pembrolizumab, umbralisib)
arm group type: Experimental
description: Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Pembrolizumab
description: Given IV
arm group label: Treatment (pembrolizumab, umbralisib)
other name: Immunoglobulin G4
other name: Anti-(Human Programmed Cell Death 1)
other name: Lambrolizumab
other name: MK-3475
other name: SCH 900475
intervention type: Drug
intervention name: Umbralisib
description: Given PO
arm group label: Treatment (pembrolizumab, umbralisib)
other name: TGR-1202
other name: RP5264
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ryan Lynch
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: Ryan Lynch
investigator title: Assistant Professor
mesh term: Lymphoma
mesh term: Hodgkin Disease
mesh term: Pembrolizumab
mesh term: Immunoglobulins
mesh term: Immunoglobulin G
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 