<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/NCT02203604</url>
  </required_header>
  <id_info>
    <org_study_id>091309</org_study_id>
    <secondary_id>NCI-2014-01306</secondary_id>
    <secondary_id>CA184-084</secondary_id>
    <secondary_id>Pro20140000135</secondary_id>
    <secondary_id>P30CA072720</secondary_id>
    <secondary_id>Pro20140000135</secondary_id>
    <nct_id>NCT02203604</nct_id>
  </id_info>
  <brief_title>High-Dose Aldesleukin and Ipilimumab in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed By Surgery</brief_title>
  <official_title>A Phase II Single Arm Study of High-Dose IL-2 and Ipilimumab in Patients With Unresectable Stage III and Stage IV Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CINJRegulatory</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rutgers Cancer Institute of New Jersey</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Rutgers, The State University of New Jersey</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well high-dose aldesleukin and ipilimumab works in treating&#xD;
      patients with stage III-IV melanoma that cannot be removed by surgery. Biological therapies,&#xD;
      such as aldesleukin, may stimulate or suppress the immune system in different ways and stop&#xD;
      tumor cells from growing. Monoclonal antibodies, such as ipilimumab, interfere with the&#xD;
      ability of tumor cells to grow and spread. Giving high-dose aldesleukin together with&#xD;
      ipilimumab may work better in treating patients with melanoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. The best overall response rate within the first 24 weeks of combination interleukin (IL)-2&#xD;
      (aldesleukin) and ipilimumab using the immune-related response criteria.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Best overall response (BOR). II. Progression-free survival (PFS). III. Disease control&#xD;
      rate (DCR). IV. Overall survival. V. To collect data on the safety and feasibility of&#xD;
      combined high-dose IL-2 and ipilimumab.&#xD;
&#xD;
      VI. To evaluate the cluster of differentiation (CD)4+ and CD8+ T cell response in the tumor&#xD;
      microenvironment and peripheral blood of patients treated on this study.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      INDUCTION: Patients receive ipilimumab intravenously (IV) over 90 minutes on days 1, 22, 43,&#xD;
      and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.&#xD;
&#xD;
      MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable&#xD;
      toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 36 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Insufficient rate of accrual&#xD;
  </why_stopped>
  <start_date type="Actual">November 26, 2014</start_date>
  <completion_date type="Actual">January 27, 2020</completion_date>
  <primary_completion_date type="Actual">January 27, 2020</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 as Determined by mWHO Criteria</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>Defined as the ratio of the number of participants whose number of participants whose best response is a complete response or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.&quot;, or similar definition that is accurate and appropriate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0</measure>
    <time_frame>Up to 60 weeks</time_frame>
    <description>The number of participants with adverse in each classification of severity and relationship to treatment will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Time from the date of registration to the date of death from any cause, assessed up to 3 years</time_frame>
    <description>number of until death from any cause after the start of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Count of Participants With Increased Effector CD8+ T Cells</measure>
    <time_frame>Time from the date of registration until the date of documented disease progression or death, assessed up to up to 104 weeks</time_frame>
    <description>Count of participants from the date of diagnosis or the start of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response, Defined as the Best Response Across All Time Points</measure>
    <time_frame>After the first 24 weeks</time_frame>
    <description>Best overall response was defined as participants who achieved a complete or partial overall response as assessed by the Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Count of Participants With Increased Effector CD8+ T Cells - Frequency of Effector CD8+ T Cells</measure>
    <time_frame>Up to 104 weeks</time_frame>
    <description>Treatment effect for each patient will be measured as paired differences between pre and post measurements of these parameters at various times. Transformation of the data will be performed if appropriate, e.g. log transformation, and hence treatment effect will be expressed on a log scale. Data relating to immune response will be presented as descriptive summary statistics (such as mean, standard error and 90% confidence intervals [CI]).&#xD;
The purity of the CD8+ T cells can then be measured via flow cytometry next the cells are counted and categorized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of CD4+FoxP3+ Regulatory T Cells</measure>
    <time_frame>Up to 104 weeks</time_frame>
    <description>Treatment effect for each patient will be measured as paired differences between pre and post measurements of these parameters at various times. Transformation of the data will be performed if appropriate, e.g. log transformation, and hence treatment effect will be expressed on a log scale. Data relating to immune response will be presented as descriptive summary statistics (such as mean, standard error and 90% CI).Using flow cytometry.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Recurrent Melanoma</condition>
  <condition>Stage IIIA Melanoma</condition>
  <condition>Stage IIIB Melanoma</condition>
  <condition>Stage IIIC Melanoma</condition>
  <condition>Stage IV Melanoma</condition>
  <arm_group>
    <arm_group_label>Treatment (aldesleukin, ipilimumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.&#xD;
MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>aldesleukin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (aldesleukin, ipilimumab)</arm_group_label>
    <other_name>IL-2</other_name>
    <other_name>Proleukin</other_name>
    <other_name>recombinant human interleukin-2</other_name>
    <other_name>recombinant interleukin-2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ipilimumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (aldesleukin, ipilimumab)</arm_group_label>
    <other_name>anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody</other_name>
    <other_name>MDX-010</other_name>
    <other_name>MDX-CTLA-4</other_name>
    <other_name>monoclonal antibody CTLA-4</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (aldesleukin, ipilimumab)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to give written informed consent&#xD;
&#xD;
          -  Histologic or cytologic diagnosis of cutaneous melanoma that is considered&#xD;
             unresectable (stage III) or metastatic (stage IV); ocular and mucosal melanoma is&#xD;
             excluded&#xD;
&#xD;
          -  White blood cell (WBC) &gt;= 2000/uL&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000/uL&#xD;
&#xD;
          -  Platelets &gt;= 75 x 10^3/uL&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL (&gt;= 80 g/L; may be transfused)&#xD;
&#xD;
          -  Creatinine =&lt; 2.0 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =&lt; 2.5 x ULN for&#xD;
             patients without liver metastasis, =&lt; 5 times for patients with liver metastases&#xD;
&#xD;
          -  Bilirubin =&lt; 2.0 x ULN, (except patients with Gilbert's syndrome, who must have a&#xD;
             total bilirubin less than 3.0 mg/dL)&#xD;
&#xD;
          -  No known active or chronic infection with human immunodeficiency virus (HIV),&#xD;
             hepatitis B, or hepatitis C; testing is not required unless clinically suspected&#xD;
&#xD;
          -  Performance status (Eastern Cooperative Oncology Group [ECOG] 0-1)&#xD;
&#xD;
          -  Patients must have a life expectancy of greater than three months at the start of the&#xD;
             trial&#xD;
&#xD;
          -  Patients must have a brain magnetic resonance imaging (MRI) that is free of active&#xD;
             metastases; metastases that have been treated with radiation or surgical resection,&#xD;
             are stable for at least 4 weeks and do not require steroids are eligible&#xD;
&#xD;
          -  Patients may have received treatment of completely resected early stage melanoma,&#xD;
             comprising interferon, radiation treatment, or experimental vaccine therapy, and in&#xD;
             the metastatic setting patient can have had treatment such as chemotherapy,&#xD;
             immunotherapy (except prior treatment with ipilimumab and IL-2), and other&#xD;
             experimental agent which was completed 4 weeks prior to enrollment&#xD;
&#xD;
          -  Normal cardiac stress test for patients over 50 years of age&#xD;
&#xD;
          -  Forced expiratory volume in 1 second (FEV1) &gt; 65% of prediction for those patients&#xD;
             with extensive pulmonary metastases or chronic pulmonary disease history&#xD;
&#xD;
          -  Forced vital capacity (FVC) &gt; 65% of prediction for those patients with extensive&#xD;
             pulmonary metastases or chronic pulmonary disease history&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) must be using an adequate method of&#xD;
             contraception to avoid pregnancy throughout the study and for up to 26 weeks after the&#xD;
             last dose of investigational product, in such a manner that the risk of pregnancy is&#xD;
             minimized; in general, the decision for appropriate methods to prevent pregnancy&#xD;
             should be determined by discussions between the investigator and the study subject;&#xD;
             WOCBP include any female who has experienced menarche and who has not undergone&#xD;
             successful surgical sterilization (hysterectomy, bilateral tubal ligation, or&#xD;
             bilateral oophorectomy) or is not post-menopausal; post-menopause is defined as:&#xD;
&#xD;
               -  Amenorrhea &gt;= 12 consecutive months without another cause, or&#xD;
&#xD;
               -  For women with irregular menstrual periods and taking hormone replacement therapy&#xD;
                  (HRT), a documented serum follicle stimulating hormone (FSH) level &gt;= 35 mIU/mL&#xD;
&#xD;
               -  Women who are using oral contraceptives, other hormonal contraceptives (vaginal&#xD;
                  products, skin patches, or implanted or injectable products), or mechanical&#xD;
                  products such as an intrauterine device or barrier methods (diaphragm, condoms,&#xD;
                  spermicides) to prevent pregnancy, or are practicing abstinence or where their&#xD;
                  partner is sterile (eg, vasectomy) should be considered to be of childbearing&#xD;
                  potential&#xD;
&#xD;
               -  WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25&#xD;
                  IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours&#xD;
                  before the start of ipilimumab&#xD;
&#xD;
               -  Men of fathering potential must be using an adequate method of contraception to&#xD;
                  avoid conception throughout the study (and for up to 26 weeks after the last dose&#xD;
                  of investigational product) in such a manner that the risk of pregnancy is&#xD;
                  minimized&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any other malignancy form which the patient has been disease-free for less than 5&#xD;
             years, with the exception of adequately treated and cured basal or squamous cell skin&#xD;
             cancer, superficial bladder cancer or carcinoma in situ of the cervix&#xD;
&#xD;
          -  Patients with primary ocular or mucosal melanoma are excluded&#xD;
&#xD;
          -  Patients with a history of inflammatory bowel disease, including ulcerative colitis&#xD;
             and Crohn's disease, are excluded from this study, as are patients with a history of&#xD;
             symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis&#xD;
             [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's&#xD;
             granulomatosis]); motor neuropathy considered of autoimmune origin (e.g.&#xD;
             Guillain-Barre syndrome and Myasthenia Gravis)&#xD;
&#xD;
          -  Any underlying medical or psychiatric condition, which in the opinion of the&#xD;
             investigator will make the administration of ipilimumab hazardous or obscure the&#xD;
             interpretation of adverse events (AEs), such as a condition associated with frequent&#xD;
             diarrhea&#xD;
&#xD;
          -  Patients with underlying heart conditions who are deemed ineligible for surgery by&#xD;
             cardiology consult; patients with reversible ischemic changes on cardiac stress test&#xD;
&#xD;
          -  Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to&#xD;
             1 month before or after any dose of ipilimumab)&#xD;
&#xD;
          -  A history of prior treatment with IL-2, ipilimumab or prior cytotoxic T-lymphocyte&#xD;
             antigen 4 (CTLA4) inhibitor or agonist&#xD;
&#xD;
          -  Concomitant therapy with any of the following: interferon, or other non-study&#xD;
             immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other&#xD;
             investigation therapies; or chronic use of systemic corticosteroids&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP), who:&#xD;
&#xD;
               -  Are unwilling or unable to use an acceptable method of contraception to avoid&#xD;
                  pregnancy for their entire study period and for at least 8 weeks after cessation&#xD;
                  of study drug, or&#xD;
&#xD;
               -  Have a positive pregnancy test at baseline, or&#xD;
&#xD;
               -  Are pregnant or breastfeeding&#xD;
&#xD;
          -  Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for&#xD;
             treatment of either a psychiatric or physical (eg, infectious) illness&#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>Howard Kaufman</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rutgers Cancer Institute of New Jersey</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Loyola University Medical Center</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <results_first_submitted>September 1, 2022</results_first_submitted>
  <results_first_submitted_qc>May 24, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 18, 2023</results_first_posted>
  <last_update_submitted>July 3, 2023</last_update_submitted>
  <last_update_submitted_qc>July 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rutgers, The State University of New Jersey</investigator_affiliation>
    <investigator_full_name>CINJRegulatory</investigator_full_name>
    <investigator_title>CINJ Clinical Trial Administrator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aldesleukin</mesh_term>
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Ipilimumab</mesh_term>
    <mesh_term>Interleukin-2</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</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: SAP Protocol_1</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>August 11, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT02203604/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan: SAP Protocol_2</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>August 11, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT02203604/Prot_SAP_001.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>September 17, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT02203604/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Aldesleukin, Ipilimumab)</title>
          <description>INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.&#xD;
MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
aldesleukin: Given IV&#xD;
ipilimumab: Given IV&#xD;
laboratory biomarker analysis: Correlative studies</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </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 (Aldesleukin, Ipilimumab)</title>
          <description>INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.&#xD;
MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
aldesleukin: Given IV&#xD;
ipilimumab: Given IV&#xD;
laboratory biomarker analysis: Correlative studies</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
          </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="0"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </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="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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </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>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate as Determined by mWHO Criteria</title>
        <description>Defined as the ratio of the number of participants whose number of participants whose best response is a complete response or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.&quot;, or similar definition that is accurate and appropriate.</description>
        <time_frame>Up to 24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Objective Response Rate as Determined by mWHO Criteria</title>
            <description>Defined as the ratio of the number of participants whose number of participants whose best response is a complete response or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.&#xD;
Up to 24 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate as Determined by mWHO Criteria</title>
          <description>Defined as the ratio of the number of participants whose number of participants whose best response is a complete response or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.&quot;, or similar definition that is accurate and appropriate.</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="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0</title>
        <description>The number of participants with adverse in each classification of severity and relationship to treatment will be reported.</description>
        <time_frame>Up to 60 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Aldesleukin, Ipilimumab)</title>
            <description>INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.&#xD;
MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
aldesleukin: Given IV&#xD;
ipilimumab: Given IV&#xD;
laboratory biomarker analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0</title>
          <description>The number of participants with adverse in each classification of severity and relationship to treatment will be reported.</description>
          <units>participants</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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>number of until death from any cause after the start of treatment</description>
        <time_frame>Time from the date of registration to the date of death from any cause, assessed up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Aldesleukin, Ipilimumab)</title>
            <description>INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.&#xD;
MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
aldesleukin: Given IV&#xD;
ipilimumab: Given IV&#xD;
laboratory biomarker analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>number of until death from any cause after the start 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="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Participants With Increased Effector CD8+ T Cells</title>
        <description>Count of participants from the date of diagnosis or the start of treatment.</description>
        <time_frame>Time from the date of registration until the date of documented disease progression or death, assessed up to up to 104 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Aldesleukin, Ipilimumab)</title>
            <description>INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.&#xD;
MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
aldesleukin: Given IV&#xD;
ipilimumab: Given IV&#xD;
laboratory biomarker analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Participants With Increased Effector CD8+ T Cells</title>
          <description>Count of participants from the date of diagnosis or the start 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="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Best Overall Response, Defined as the Best Response Across All Time Points</title>
        <description>Best overall response was defined as participants who achieved a complete or partial overall response as assessed by the Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions</description>
        <time_frame>After the first 24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Objective Response Rate as Determined by mWHO Criteria</title>
            <description>Defined as the ratio of the number of participants whose best response is a complete response or partial response divided by the total number of participants enrolled who have baseline and post-treatment assessments.&#xD;
Up to 24 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response, Defined as the Best Response Across All Time Points</title>
          <description>Best overall response was defined as participants who achieved a complete or partial overall response as assessed by the Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions</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="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Participants With Increased Effector CD8+ T Cells - Frequency of Effector CD8+ T Cells</title>
        <description>Treatment effect for each patient will be measured as paired differences between pre and post measurements of these parameters at various times. Transformation of the data will be performed if appropriate, e.g. log transformation, and hence treatment effect will be expressed on a log scale. Data relating to immune response will be presented as descriptive summary statistics (such as mean, standard error and 90% confidence intervals [CI]).&#xD;
The purity of the CD8+ T cells can then be measured via flow cytometry next the cells are counted and categorized.</description>
        <time_frame>Up to 104 weeks</time_frame>
        <population>Data was not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Aldesleukin, Ipilimumab)</title>
            <description>INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.&#xD;
MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
aldesleukin: Given IV&#xD;
ipilimumab: Given IV&#xD;
laboratory biomarker analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Participants With Increased Effector CD8+ T Cells - Frequency of Effector CD8+ T Cells</title>
          <description>Treatment effect for each patient will be measured as paired differences between pre and post measurements of these parameters at various times. Transformation of the data will be performed if appropriate, e.g. log transformation, and hence treatment effect will be expressed on a log scale. Data relating to immune response will be presented as descriptive summary statistics (such as mean, standard error and 90% confidence intervals [CI]).&#xD;
The purity of the CD8+ T cells can then be measured via flow cytometry next the cells are counted and categorized.</description>
          <population>Data was not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency of CD4+FoxP3+ Regulatory T Cells</title>
        <description>Treatment effect for each patient will be measured as paired differences between pre and post measurements of these parameters at various times. Transformation of the data will be performed if appropriate, e.g. log transformation, and hence treatment effect will be expressed on a log scale. Data relating to immune response will be presented as descriptive summary statistics (such as mean, standard error and 90% CI).Using flow cytometry.</description>
        <time_frame>Up to 104 weeks</time_frame>
        <population>Data was not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Aldesleukin, Ipilimumab)</title>
            <description>INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.&#xD;
MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
aldesleukin: Given IV&#xD;
ipilimumab: Given IV&#xD;
laboratory biomarker analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of CD4+FoxP3+ Regulatory T Cells</title>
          <description>Treatment effect for each patient will be measured as paired differences between pre and post measurements of these parameters at various times. Transformation of the data will be performed if appropriate, e.g. log transformation, and hence treatment effect will be expressed on a log scale. Data relating to immune response will be presented as descriptive summary statistics (such as mean, standard error and 90% CI).Using flow cytometry.</description>
          <population>Data was not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected over a period of three years.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Aldesleukin, Ipilimumab)</title>
          <description>INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.&#xD;
MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
aldesleukin: Given IV&#xD;
ipilimumab: Given IV&#xD;
laboratory biomarker analysis: Correlative studies</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="4" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="6" subjects_at_risk="9"/>
              </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="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Thrombotic thrombocytopenic purpura</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>External ear inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Scleral disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Gastrointestinal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </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" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </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="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythroderma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Periorbital edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
              </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>
    <limitations_and_caveats>The trial was closed early due to slow accrual. Early termination lead to a small number of subjects analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Ann Silk, MD</name_or_title>
      <organization>Dana Farber Cancer Institute</organization>
      <phone>617-632-6571</phone>
      <email>Ann_Silk@dfci.harvard.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/NCT02203604
org study id: 091309
secondary id: NCI-2014-01306
secondary id: CA184-084
secondary id: Pro20140000135
secondary id: P30CA072720
secondary id: Pro20140000135
nct id: NCT02203604
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This phase II trial studies how well high-dose aldesleukin and ipilimumab works in treating
      patients with stage III-IV melanoma that cannot be removed by surgery. Biological therapies,
      such as aldesleukin, may stimulate or suppress the immune system in different ways and stop
      tumor cells from growing. Monoclonal antibodies, such as ipilimumab, interfere with the
      ability of tumor cells to grow and spread. Giving high-dose aldesleukin together with
      ipilimumab may work better in treating patients with melanoma.
PRIMARY OBJECTIVES:

      I. The best overall response rate within the first 24 weeks of combination interleukin (IL)-2
      (aldesleukin) and ipilimumab using the immune-related response criteria.

      SECONDARY OBJECTIVES:

      I. Best overall response (BOR). II. Progression-free survival (PFS). III. Disease control
      rate (DCR). IV. Overall survival. V. To collect data on the safety and feasibility of
      combined high-dose IL-2 and ipilimumab.

      VI. To evaluate the cluster of differentiation (CD)4+ and CD8+ T cell response in the tumor
      microenvironment and peripheral blood of patients treated on this study.

      OUTLINE:

      INDUCTION: Patients receive ipilimumab intravenously (IV) over 90 minutes on days 1, 22, 43,
      and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.

      MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable
      toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 36 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate as Determined by mWHO Criteria
time frame: Up to 24 weeks
description: Defined as the ratio of the number of participants whose number of participants whose best response is a complete response or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.
measure: Number of Participants With Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
time frame: Up to 60 weeks
description: The number of participants with adverse in each classification of severity and relationship to treatment will be reported.
measure: Overall Survival
time frame: Time from the date of registration to the date of death from any cause, assessed up to 3 years
description: number of until death from any cause after the start of treatment
measure: Count of Participants With Increased Effector CD8+ T Cells
time frame: Time from the date of registration until the date of documented disease progression or death, assessed up to up to 104 weeks
description: Count of participants from the date of diagnosis or the start of treatment.
measure: Best Overall Response, Defined as the Best Response Across All Time Points
time frame: After the first 24 weeks
description: Best overall response was defined as participants who achieved a complete or partial overall response as assessed by the Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions
measure: Count of Participants With Increased Effector CD8+ T Cells - Frequency of Effector CD8+ T Cells
time frame: Up to 104 weeks
description: Treatment effect for each patient will be measured as paired differences between pre and post measurements of these parameters at various times. Transformation of the data will be performed if appropriate, e.g. log transformation, and hence treatment effect will be expressed on a log scale. Data relating to immune response will be presented as descriptive summary statistics (such as mean, standard error and 90% confidence intervals [CI]).
The purity of the CD8+ T cells can then be measured via flow cytometry next the cells are counted and categorized.
measure: Frequency of CD4+FoxP3+ Regulatory T Cells
time frame: Up to 104 weeks
description: Treatment effect for each patient will be measured as paired differences between pre and post measurements of these parameters at various times. Transformation of the data will be performed if appropriate, e.g. log transformation, and hence treatment effect will be expressed on a log scale. Data relating to immune response will be presented as descriptive summary statistics (such as mean, standard error and 90% CI).Using flow cytometry.
arm group label: Treatment (aldesleukin, ipilimumab)
arm group type: Experimental
description: INDUCTION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 and high-dose aldesleukin IV on days 22-26 and 43-47.
MAINTENANCE: Beginning on weeks 24, patients without disease progression or unacceptable toxicity receive ipilimumab IV over 90 minutes once every 12 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: aldesleukin
description: Given IV
arm group label: Treatment (aldesleukin, ipilimumab)
other name: IL-2
other name: Proleukin
other name: recombinant human interleukin-2
other name: recombinant interleukin-2
intervention type: Biological
intervention name: ipilimumab
description: Given IV
arm group label: Treatment (aldesleukin, ipilimumab)
other name: anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
other name: MDX-010
other name: MDX-CTLA-4
other name: monoclonal antibody CTLA-4
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Treatment (aldesleukin, ipilimumab)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Howard Kaufman
role: Principal Investigator
affiliation: Rutgers Cancer Institute of New Jersey
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Rutgers, The State University of New Jersey
investigator full name: CINJRegulatory
investigator title: CINJ Clinical Trial Administrator
mesh term: Melanoma
mesh term: Aldesleukin
mesh term: Antineoplastic Agents, Immunological
mesh term: Ipilimumab
mesh term: Interleukin-2
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The trial was closed early due to slow accrual. Early termination lead to a small number of subjects analyzed.
point of contact: 