<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/NCT03759184</url>
  </required_header>
  <id_info>
    <org_study_id>190024</org_study_id>
    <secondary_id>19-C-0024</secondary_id>
    <nct_id>NCT03759184</nct_id>
  </id_info>
  <brief_title>Human IL-15 (rhIL-15) and Obinutuzumab for Relapsed and Refractory Chronic Lymphocyte Leukemia</brief_title>
  <official_title>Phase 1 Trial of Human IL-15 (rhIL-15) and Obinutuzumab for Relapsed and Refractory Chronic Lymphocyte Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <has_dmc>No</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>
      Background:&#xD;
&#xD;
      Chronic lymphocytic leukemia (CLL) is a blood cancer. Recombinant human interleukin 15&#xD;
      (IL-15) is a manmade protein. Obinutuzumab is a protein made to deactivate cancer cells.&#xD;
      Researchers want to see if treating people with CLL with both proteins improves their&#xD;
      outcomes.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To find the safe dose of IL-15 with Obinutuzumab. To identify its effects, including on the&#xD;
      immune system and cancer.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Adults at least 18 years old who have certain CLL that standard therapy has failed&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with:&#xD;
&#xD;
        -  Medical history&#xD;
&#xD;
        -  Physical exam&#xD;
&#xD;
        -  Evaluation of ability to do daily activities&#xD;
&#xD;
        -  Blood, heart, and urine tests&#xD;
&#xD;
      Participants may also be screened with:&#xD;
&#xD;
        -  A small amount of bone marrow removed by needle in the hipbone&#xD;
&#xD;
        -  Scans of the body and/or brain&#xD;
&#xD;
      The study will be done in 28-day cycles for up to 6 cycles.&#xD;
&#xD;
      Participants will get the study drugs through a catheter and pump.&#xD;
&#xD;
      Cycle 1: Participants will be seen in the clinic during week 1. They will get:&#xD;
&#xD;
        -  IL-15 as a continuous intravenous infusion over 24 hours on days 1-5 and 3 dose levels&#xD;
           will be evaluated: dose level 1; 0.5 mcg/kg/day; dose level 2: 1 mcg/kg/day and dose&#xD;
           level 3: 2 mcg/kg/day.&#xD;
&#xD;
        -  Obinutuzumab as a 4-hour infusion in escalating doses during the course of the first&#xD;
           cycle 100 mg on day 4, 900 mg on day 5, 1000 mg on day 11 and day 18.&#xD;
&#xD;
      Cycles 2 through 6: Participants will come to the clinic days 1-5 and get IL-15 as in cycle 1&#xD;
      and Obinutuzumab 1000 mg on day 4 of each treatment cycle.&#xD;
&#xD;
      During the study, participants:&#xD;
&#xD;
        -  Will repeat screening tests&#xD;
&#xD;
        -  Will get standard medicines for side effects&#xD;
&#xD;
        -  May give blood, saliva, and tumor samples for research&#xD;
&#xD;
      After treatment, participants will have follow-up visits every 3 months for 1 year, then&#xD;
      every 6 months for up to 5 years. After that, participants may be called or emailed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
        -  Of the several drugs and drug combinations approved for treatment of relapsed and&#xD;
           refractory chronic lymphocytic leukemia (CLL), the reported complete response rates are&#xD;
           no greater than 30%.&#xD;
&#xD;
        -  Obinutuzumab is a glycoengineered, humanized type 2 anti-cluster of differentiation 20&#xD;
           (CD20) monoclonal antibody thought to engage the immune system by directly activating&#xD;
           antibody-dependent, cell mediated cytotoxicity (ADCC); it is approved for treatment of&#xD;
           chronic lymphocytic leukemia in combination with chlorambucil.&#xD;
&#xD;
        -  The key mediators of ADCC are polymorphonuclear neutrophils, monocytes, and natural&#xD;
           killer (NK) cells.&#xD;
&#xD;
        -  Recombinant human Interleukin-15 (rhIL-15) is a stimulatory cytokine that promotes the&#xD;
           differentiation and activation of NK cells, monocytes, and long-term cluster of&#xD;
           differentiation 8 (CD8) + memory T-cells. In a Phase I trial, administration of rhIL-15&#xD;
           as a 5-day continuous intravenous infusion (civ) was associated with up to 45-fold&#xD;
           increase in the number of NK cells at well tolerated dose levels.&#xD;
&#xD;
        -  Preclinical murine lymphoid malignancy models have shown increased efficacy of&#xD;
           monoclonal antibodies when administered together with recombinant human Interleukin-15&#xD;
           (rhIL-15); BL/6 mice inoculated with EL4 murine T-cell lymphoma expressing human cluster&#xD;
           of differentiation 20 (EL4-CD20) cells (a syngeneic lymphoma line); including&#xD;
           significant prolongation of survival with the IL-15/Rituximab combination compared to&#xD;
           either drug given as single agent (90% v. 30% alive at 75 days).&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To determine the safety, toxicity profile, dose-limiting toxicity (DLT) and the maximum&#xD;
      tolerated dose (MTD) of civ rhIL-15 administration in combination with intravenous (IV)&#xD;
      Obinutuzumab treatment&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Age greater than or equal to 18 years old&#xD;
&#xD;
        -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1&#xD;
&#xD;
        -  Diagnosis of chronic lymphocytic leukemia (CLL) with greater than or equal to 50% of B&#xD;
           cells expressing CD20&#xD;
&#xD;
        -  Patients must have measurable or evaluable disease&#xD;
&#xD;
        -  Patients must have CLL that is refractory or relapsed following therapy with a Bruton's&#xD;
           tyrosine kinase (BTK) inhibitor OR have relapsed/refractory CLL and are intolerant to&#xD;
           BTK inhibitor therapy; patients with deletion 17p (del(17p) must also be refractory or&#xD;
           relapsed after, or intolerant to, therapy with Venetoclax&#xD;
&#xD;
        -  Adequate organ function parameters as defined within the protocol&#xD;
&#xD;
        -  Active disease requiring treatment, as defined within the protocol&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  This is a single institution non-randomized Phase I dose escalation study evaluating&#xD;
           increasing doses of civ rhIL-15 in combination with Obinutuzumab using a standard 3 + 3&#xD;
           dose escalation design.&#xD;
&#xD;
        -  On days 1-5 of each 4-week cycle, rhIL-15 will be administered by civ at dose levels&#xD;
           0.5, 1, and 2 mcg/kg/day.&#xD;
&#xD;
        -  During the first cycle, Obinutuzumab will be administered at a dose of 100 mg by IV on&#xD;
           day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18: then 1,000 mg on day&#xD;
           4 of each subsequent cycle.&#xD;
&#xD;
        -  Infusion reaction, antimicrobial, and tumor lysis syndrome prophylaxis will be&#xD;
           administered per manufacturers recommendations.&#xD;
&#xD;
        -  Treatment will continue up to 6 cycles, or until unacceptable toxicity or progressive&#xD;
           disease.&#xD;
&#xD;
        -  Up to 24 patients will be enrolled in the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was closed after &gt; 1 year of inactivity.&#xD;
  </why_stopped>
  <start_date type="Actual">July 11, 2019</start_date>
  <completion_date type="Actual">October 22, 2021</completion_date>
  <primary_completion_date type="Actual">December 15, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Treatment-emergent Adverse Events (AEs) Related to Recombinant Human Interleukin-15 (rhIL-15)</measure>
    <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
    <description>Here is the number of treatment-emergent AEs related to rhIL-15 assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A treatment emergent AE is defined as</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Treatment-emergent Adverse Events (AEs) Related to Obinutuzumab</measure>
    <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
    <description>Here is the number of treatment-emergent AEs related to Obinutuzumab assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A treatment emergent AE is defined as</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With a Grades 3-5 Dose-limiting Toxicity (DLT) of Continuous Intravenous (CIV) Recombinant Human Interleukin-15 (rhIL-15) Treatment</measure>
    <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
    <description>A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to interleukin-15 by the principal investigator during the first 28 days of treatment. Some exceptions are grade 3 or 4 lymphocytopenia or neutropenia without clinical signs of infection grade 2 or above, grade 3 or 4 thrombocytopenia lasting fewer than 5 days and not associated with bleeding or purpura. Transient (&lt;24 hours) grade 3 hypoalbuminemia, hypokalemia, hypomagnesemia, hyponatremia or hypophosphatemia which responds to medical intervention. Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With a Grade 3-5 Dose-limiting Toxicity (DLT) With Intravenous (IV) Obinutuzumab Treatment</measure>
    <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
    <description>A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to Obinutuzumab by the principal investigator during the first 28 days of treatment. Some exceptions are grade 3 or 4 lymphocytopenia or neutropenia without clinical signs of infection grade 2 or above, grade 3 or 4 thrombocytopenia lasting fewer than 5 days and not associated with bleeding or purpura. Transient (&lt;24 hours) grade 3 hypoalbuminemia, hypokalemia, hypomagnesemia, hyponatremia or hypophosphatemia which responds to medical intervention. Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) Administration</measure>
    <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
    <description>The MTD is the dose level at which no more than 1 of up to 6 participants experience a dose limiting toxicity (DLT) during the DLT evaluation window, or the dose at which at least 2 of ≤ 6 participants have DLT. A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to interleukin-15 by the principal investigator during the first 28 days of treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD) of Intravenous (IV) Obinutuzumab Treatment</measure>
    <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
    <description>The MTD is the dose level at which no more than 1 of up to 6 participants experience a dose limiting toxicity (DLT) during the DLT evaluation window, or the dose at which at least 2 of ≤ 6 participants have DLT. A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to Obinutuzumab by the principal investigator during the first 28 days of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>time measurement criteria are met for CR, CRi, or PR whichever is recorded first until the first date that recurrent of progressive disease is objectively documented or death, approximately 27 months</time_frame>
    <description>DOR is measured from the time measurement criteria are met for complete response (CR), complete response with incomplete marrow recovery (CRi), or partial response (PR) whichever is recorded first until the first date that recurrent of progressive disease is objectively documented, death, or in the absence of progressive disease (PD), date of last assessment. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. Complete response (CR) is disease related constitutional symptoms resolved; partial response (PR) is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met; complete response with incomplete marrow recovery (CRi) is CR with incomplete hematopoietic recovery; stable disease (SD) is defined as not achieving CR or PR, and PD is development of transformation to a more aggressive histology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>6 cycles (each cycle is 28 days or 4 weeks)</time_frame>
    <description>Overall response is defined as the best response recorded from the start of the treatment until disease progression/recurrence. OS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. Complete response (CR) is disease related constitutional symptoms resolved; Partial response (PR) is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met, requires the absence of growth factor or transfusion support; Complete response with incomplete marrow recovery (CRi) is CR with incomplete hematopoietic recovery; Stable disease (SD) is defined as not achieving CR or PR, but not fulfilling the criteria for progressive disease (PD); and PD is one criteria from Group A or B are met or development of transformation to a more aggressive histology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free Survival (EFS)</measure>
    <time_frame>Approximately 8 months</time_frame>
    <description>EFS is defined as the duration of time from the date of study enrollment until time of disease lapse, disease progression, alternative therapy for lymphoma given, or death, whichever comes first. EFS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Progression was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines and is defined as one criterion from Group A (e.g., lymphadenopathy or liver and/or spleen size) or B (e.g., platelet count) are met or development of transformation to a more aggressive histology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Approximately 27 months</time_frame>
    <description>OS is defined as the date of on-study to the date of death from any cause or last follow up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Approximately 8 months</time_frame>
    <description>PFS is defined as the duration of time measurement criteria are met for complete response (CR), complete response with incomplete marrow recovery (CRi), and partial response (PR), whichever is recorded first. PFS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. CR is disease related constitutional symptoms resolved; PR is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met, requires the absence of growth factor or transfusion support; CRi is CR with incomplete hematopoietic recovery; and progressive disease is one criteria from Group A or B are met or development of transformation to a more aggressive histology.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).</measure>
    <time_frame>Date treatment consent signed to date off study, approximately 27 months and 11 days.</time_frame>
    <description>Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Leukemia</condition>
  <condition>Lymphocytic</condition>
  <condition>Chronic</condition>
  <condition>B-Cell</condition>
  <arm_group>
    <arm_group_label>Arm 1 -DOSE ESCALATION</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DOSE ESCALATION: Interleukin-15 (IL-15) by continuous intravenous (civ) infusion at escalating doses of 0.5, 1, and 2 mcg/kg/day on days 1-5 of each 4-week cycle (max 6 cycles), with Obinutuzumab by IV infusion at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of the first cycle; then 1,000 mg on day 4 of each subsequent cycle, to determine the maximum tolerated dose (MTD)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 - DOSE EXPANSION</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DOSE EXPANSION: 3 to 6 patients to receive interleukin-15 (IL-15) by continuous intravenous (civ) infusion at the maximum tolerated dose (MTD) on days 1-5 of cycles 1-6 with Obinutuzumab by IV infusion at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of the first cycle; then 1,000 mg on day 4 of each subsequent cycle (Total 9 patients at MTD)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rhIL-15</intervention_name>
    <description>Continuous intravenous (civ) Interleukin-15 (IL-15) at dose levels of 0.5,1 or 2 mcg/kg/day on days 1-5 of cycles 1-6</description>
    <arm_group_label>Arm 1 -DOSE ESCALATION</arm_group_label>
    <other_name>Recombinant human interleukin-15</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rhIL-15</intervention_name>
    <description>Continuous intravenous (civ) Interleukin-15 (IL-15) at the maximum tolerated dose or the maximum administered dose of 2 mcg/kg/day on days 1-5 of cycles 1-6</description>
    <arm_group_label>Arm 2 - DOSE EXPANSION</arm_group_label>
    <other_name>Recombinant human interleukin-15</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Obinutuzumab</intervention_name>
    <description>Intravenous (IV) Obinutuzumab will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle</description>
    <arm_group_label>Arm 1 -DOSE ESCALATION</arm_group_label>
    <arm_group_label>Arm 2 - DOSE EXPANSION</arm_group_label>
    <other_name>Gazyva</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Patients must have a confirmed diagnosis of chronic lymphocytic leukemia/small&#xD;
             lymphocytic lymphoma that expresses cluster of differentiation 20 (CD20) as confirmed&#xD;
             by new/fresh peripheral blood sample collection and review by Laboratory of Pathology,&#xD;
             National Cancer Institute (NCI)&#xD;
&#xD;
          -  Measurable or evaluable disease&#xD;
&#xD;
          -  Patients must have received prior treatment required as follows: chronic lymphocyte&#xD;
             leukemia (CLL) that is refractory or relapsed following therapy with a Bruton's&#xD;
             tyrosine kinase (BTK) inhibitor OR have relapsed/refractory CLL and are intolerant of&#xD;
             BTK inhibitor therapy; in addition, patients with deletion 17p (del(17p) must also be&#xD;
             refractory or relapsed after, or intolerant to, therapy with Venetoclax; patients who&#xD;
             have received prior Obinutuzumab are eligible regardless of response to the drug.&#xD;
&#xD;
          -  Active disease requiring treatment, as defined by at least one of the following (per&#xD;
             the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 consensus&#xD;
             criteria):&#xD;
&#xD;
               -  Evidence of progressive marrow failure as manifested by the development of, or&#xD;
                  worsening of, anemia (hemoglobin (Hb) &lt;10 g/dL) and/or thrombocytopenia (platelet&#xD;
                  counts &lt;100x10^9/L).&#xD;
&#xD;
               -  Massive (i.e., greater than or equal to 6 centimeters (cm) below the left costal&#xD;
                  margin) or progressive or symptomatic splenomegaly.&#xD;
&#xD;
               -  Massive nodes (i.e., greater than or equal to 10 cm in longest diameter) or&#xD;
                  progressive or symptomatic lymphadenopathy.&#xD;
&#xD;
               -  Progressive lymphocytosis with an increase of greater than or equal to 50% over a&#xD;
                  2-month period, or lymphocyte doubling time (LDT) &lt;6 months.&#xD;
&#xD;
               -  Autoimmune complications including anemia or thrombocytopenia poorly responsive&#xD;
                  to corticosteroids.&#xD;
&#xD;
               -  Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung,&#xD;
                  spine).&#xD;
&#xD;
               -  Disease-related symptoms as defined by any of the following:&#xD;
&#xD;
                    -  Unintentional weight loss greater than or equal to 10% within the previous 6&#xD;
                       months.&#xD;
&#xD;
                    -  Significant fatigue (i.e., Eastern Cooperative Oncology Group (ECOG)&#xD;
                       performance scale 2 or worse; cannot work or unable to perform usual&#xD;
                       activities).&#xD;
&#xD;
                    -  Fevers 38.0 degree Celsius (C) for 2 or more weeks without evidence of&#xD;
                       infection.&#xD;
&#xD;
                    -  Night sweats for greater than or equal to 1 month without evidence of&#xD;
                       infection.&#xD;
&#xD;
          -  greater than or equal to 18 years of age on day of signing informed consent&#xD;
&#xD;
        NOTE: Because no dosing or adverse event data are currently available on the use of rhIL-15&#xD;
        in combination with Obinutuzumab in patients &lt;18 years of age, children are excluded from&#xD;
        this study, but will be eligible for future pediatric trials&#xD;
&#xD;
          -  ECOG performance status less than or equal to 1 (Karnofsky greater than or equal to&#xD;
             80%; or less than or equal to 2 (Karnofsky &gt;60%) if the decrease in the performance&#xD;
             status is CLL-related and constitutes a criterion for active treatment&#xD;
&#xD;
          -  Adequate organ function as evidenced by the following laboratory parameters:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) greater than or equal to 750 /mcL&#xD;
&#xD;
               -  Platelets greater than or equal to 50,000 / mcL (transfusions not permitted)&#xD;
&#xD;
               -  Hemoglobin greater than or equal to 9 g/dL (transfusions permitted)&#xD;
&#xD;
               -  Serum creatinine less than or equal to 1.5 X upper limit of normal (ULN)&#xD;
&#xD;
               -  Serum total bilirubin less than or equal to 1.5 X ULN OR Direct bilirubin less&#xD;
                  than or equal to upper limit of normal (ULN) for patients with total bilirubin&#xD;
                  levels &gt; 1.5 ULN&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase (SGOT)&#xD;
                  and alanine aminotransferase (ALT) Serum glutamate-pyruvate transaminase (SGPT)&#xD;
                  less than or equal to 3 X ULN&#xD;
&#xD;
          -  Women of child-bearing potential (WOCBP) and men must agree to use adequate&#xD;
             contraception (hormonal or barrier method of birth control; abstinence) prior to study&#xD;
             entry and for the duration of study treatment, and for at least 18 months after the&#xD;
             last dose of Obinutuzumab. The effects of rhIL-15 and Obinutuzumab on the developing&#xD;
             human fetus are unknown. Additionally, CD20-depleting agents are known to produce&#xD;
             opportunistic infections, causing fetal B-cell depletion in animal studies, and may be&#xD;
             teratogenic. Should a woman become pregnant or suspect she is pregnant while she or&#xD;
             her partner is participating in this study, she should inform her treating physician&#xD;
             immediately.&#xD;
&#xD;
        NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone&#xD;
        successful surgical sterilization or who is not postmenopausal. WOCBP must have a negative&#xD;
        pregnancy test (Human chorionic gonadotropin (HCG) blood or urine) during screening.&#xD;
&#xD;
        - Ability of patient to understand and the willingness to sign a written informed consent&#xD;
        document.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Current or prior anti-cancer treatment prior to the first dose of rhIL-15 as defined&#xD;
             below:&#xD;
&#xD;
               -  Chemotherapy, targeted small molecule therapy, or other anti-cancer treatment not&#xD;
                  otherwise specified below within 2 weeks&#xD;
&#xD;
               -  Radiation therapy within 2 weeks&#xD;
&#xD;
               -  Anti-cancer monoclonal antibody (mAb) treatment within 4 weeks&#xD;
&#xD;
               -  Use of an investigational agent (e.g., biologic, drug, or other) within 4 weeks&#xD;
&#xD;
               -  Allogeneic stem cell transplant within 100 days&#xD;
&#xD;
               -  Systemic treatment for graft versus host disease (GVHD), including but not&#xD;
                  limited to oral or parenteral corticosteroids, ibrutinib, and extracorporeal&#xD;
                  phototherapy, within the last 12 weeks&#xD;
&#xD;
          -  Persisting toxicity related to prior therapy (including GVHD) of grade &gt; 1, with the&#xD;
             exception of the following: alopecia or sensory neuropathy grade less than or equal to&#xD;
             2, or other grade less than or equal to 2 not constituting a safety risk based on&#xD;
             investigator's judgment&#xD;
&#xD;
          -  Current use of immunosuppressive medication, EXCEPT for the following:&#xD;
&#xD;
               -  Intranasal, inhaled, topical steroids, or local steroid injection (e.g.,&#xD;
                  intra-articular injection).&#xD;
&#xD;
               -  Systemic corticosteroids at physiologic doses less than or equal to 10 mg/day of&#xD;
                  prednisone or equivalent; or,&#xD;
&#xD;
               -  Steroids as premedication for hypersensitivity reactions (e.g., computed&#xD;
                  tomography (CT) scan premedication)&#xD;
&#xD;
          -  Presence of Richter's transformation.&#xD;
&#xD;
          -  Patients requiring immediate cytoreduction, if they had no prior treatment with a drug&#xD;
             that has an established clinical benefit.&#xD;
&#xD;
          -  Presence of uncontrolled intercurrent illnesses including but not limited to ongoing&#xD;
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             cardiac arrhythmia, cognitive impairment, active substance abuse, or psychiatric&#xD;
             illness/social situations that in the view of the Investigator would preclude safe&#xD;
             treatment and limit compliance with study requirements&#xD;
&#xD;
          -  Presence of active bacterial infections, documented human immunodeficiency virus (HIV)&#xD;
             infection, polymerase chain reaction (PCR) evidence for active or chronic hepatitis B&#xD;
             or hepatitis C, or positive screening hepatitis B virus (HBV)/ hepatitis C virus (HCV)&#xD;
             serology without documentation of successful curative treatment&#xD;
&#xD;
          -  Asthma requiring chronic inhaled or oral corticosteroids, or history of asthma&#xD;
             requiring mechanical ventilation; patients with a history of mild asthma that are on&#xD;
             or can be switched to non-corticosteroid bronchodilator regimens are eligible&#xD;
&#xD;
          -  Active or history of any autoimmune disease thought to be unrelated to their CLL&#xD;
&#xD;
          -  Inability or refusal to practice effective contraception during therapy or the&#xD;
             presence of pregnancy or active breastfeeding. Because there is no significant&#xD;
             preclinical information regarding the risks to a fetus or a newborn infant, all&#xD;
             pregnant or breastfeeding woman will be excluded from participation in this trial&#xD;
&#xD;
          -  Received a live vaccine within 30 days of planned start of study therapy. NOTE:&#xD;
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and&#xD;
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live&#xD;
             attenuated vaccines, and are not allowed&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to rhIL-15 or Obinutuzumab, unless felt to be in the best interests of the&#xD;
             patient in the opinion of the investigator&#xD;
&#xD;
          -  Known additional malignancy that requires active systemic treatment&#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>Kevin C Conlon, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2019-C-0024.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <results_first_submitted>February 15, 2022</results_first_submitted>
  <results_first_submitted_qc>February 15, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">March 10, 2022</results_first_posted>
  <last_update_submitted>March 11, 2022</last_update_submitted>
  <last_update_submitted_qc>March 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cancer Institute (NCI)</investigator_affiliation>
    <investigator_full_name>Kevin Conlon, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Monoclonal Antibody Treatment</keyword>
  <keyword>Recombinant Human Interleukin-15</keyword>
  <keyword>Lymphoid Malignancy</keyword>
  <keyword>Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obinutuzumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genome Data Sharing (GDS) plan for as long as database is active.</ipd_time_frame>
    <ipd_access_criteria>Clinical data will be made available via subscription to Biomedical Translational Research (BTRIS) and with the permission of the study principal investigator (PI).&#xD;
Genomic data are made available via database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.</ipd_access_criteria>
  </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>September 14, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT03759184/Prot_SAP_000.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>October 12, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT03759184/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>No participants were enrolled on the dose expansion phase of the study because the study was closed after &gt; 1 year of inactivity.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm 1 - Dose Escalation - Dose Level 1</title>
          <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </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>Arm 1 - Dose Escalation - Dose Level 1</title>
          <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </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="1"/>
                  </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>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.4" spread="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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="1"/>
                  </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="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Treatment-emergent Adverse Events (AEs) Related to Recombinant Human Interleukin-15 (rhIL-15)</title>
        <description>Here is the number of treatment-emergent AEs related to rhIL-15 assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A treatment emergent AE is defined as</description>
        <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment-emergent Adverse Events (AEs) Related to Recombinant Human Interleukin-15 (rhIL-15)</title>
          <description>Here is the number of treatment-emergent AEs related to rhIL-15 assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A treatment emergent AE is defined as</description>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </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>Primary</type>
        <title>Number of Treatment-emergent Adverse Events (AEs) Related to Obinutuzumab</title>
        <description>Here is the number of treatment-emergent AEs related to Obinutuzumab assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A treatment emergent AE is defined as</description>
        <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment-emergent Adverse Events (AEs) Related to Obinutuzumab</title>
          <description>Here is the number of treatment-emergent AEs related to Obinutuzumab assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A treatment emergent AE is defined as</description>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </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>Primary</type>
        <title>Number of Participants With a Grades 3-5 Dose-limiting Toxicity (DLT) of Continuous Intravenous (CIV) Recombinant Human Interleukin-15 (rhIL-15) Treatment</title>
        <description>A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to interleukin-15 by the principal investigator during the first 28 days of treatment. Some exceptions are grade 3 or 4 lymphocytopenia or neutropenia without clinical signs of infection grade 2 or above, grade 3 or 4 thrombocytopenia lasting fewer than 5 days and not associated with bleeding or purpura. Transient (&lt;24 hours) grade 3 hypoalbuminemia, hypokalemia, hypomagnesemia, hyponatremia or hypophosphatemia which responds to medical intervention. Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.</description>
        <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Grades 3-5 Dose-limiting Toxicity (DLT) of Continuous Intravenous (CIV) Recombinant Human Interleukin-15 (rhIL-15) Treatment</title>
          <description>A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to interleukin-15 by the principal investigator during the first 28 days of treatment. Some exceptions are grade 3 or 4 lymphocytopenia or neutropenia without clinical signs of infection grade 2 or above, grade 3 or 4 thrombocytopenia lasting fewer than 5 days and not associated with bleeding or purpura. Transient (&lt;24 hours) grade 3 hypoalbuminemia, hypokalemia, hypomagnesemia, hyponatremia or hypophosphatemia which responds to medical intervention. Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to 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="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3 Possibly Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 Probably Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 Definitely Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 Possibly Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 Probably Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 Definitely Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 Possibly Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 Probably Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 Definitely Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With a Grade 3-5 Dose-limiting Toxicity (DLT) With Intravenous (IV) Obinutuzumab Treatment</title>
        <description>A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to Obinutuzumab by the principal investigator during the first 28 days of treatment. Some exceptions are grade 3 or 4 lymphocytopenia or neutropenia without clinical signs of infection grade 2 or above, grade 3 or 4 thrombocytopenia lasting fewer than 5 days and not associated with bleeding or purpura. Transient (&lt;24 hours) grade 3 hypoalbuminemia, hypokalemia, hypomagnesemia, hyponatremia or hypophosphatemia which responds to medical intervention. Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.</description>
        <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Grade 3-5 Dose-limiting Toxicity (DLT) With Intravenous (IV) Obinutuzumab Treatment</title>
          <description>A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to Obinutuzumab by the principal investigator during the first 28 days of treatment. Some exceptions are grade 3 or 4 lymphocytopenia or neutropenia without clinical signs of infection grade 2 or above, grade 3 or 4 thrombocytopenia lasting fewer than 5 days and not associated with bleeding or purpura. Transient (&lt;24 hours) grade 3 hypoalbuminemia, hypokalemia, hypomagnesemia, hyponatremia or hypophosphatemia which responds to medical intervention. Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to 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="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3 Possibly Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 Probably Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 Definitely Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 Possibly Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 Probably Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 Definitely Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 Possibly Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 Probably Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 Definitely Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) Administration</title>
        <description>The MTD is the dose level at which no more than 1 of up to 6 participants experience a dose limiting toxicity (DLT) during the DLT evaluation window, or the dose at which at least 2 of ≤ 6 participants have DLT. A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to interleukin-15 by the principal investigator during the first 28 days of treatment.</description>
        <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
        <population>This outcome measure was not done. The MTD was not found because the study was closed after &gt; 1 year of inactivity and only one participant was enrolled.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) Administration</title>
          <description>The MTD is the dose level at which no more than 1 of up to 6 participants experience a dose limiting toxicity (DLT) during the DLT evaluation window, or the dose at which at least 2 of ≤ 6 participants have DLT. A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to interleukin-15 by the principal investigator during the first 28 days of treatment.</description>
          <population>This outcome measure was not done. The MTD was not found because the study was closed after &gt; 1 year of inactivity and only one participant was enrolled.</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>Primary</type>
        <title>Maximum Tolerated Dose (MTD) of Intravenous (IV) Obinutuzumab Treatment</title>
        <description>The MTD is the dose level at which no more than 1 of up to 6 participants experience a dose limiting toxicity (DLT) during the DLT evaluation window, or the dose at which at least 2 of ≤ 6 participants have DLT. A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to Obinutuzumab by the principal investigator during the first 28 days of treatment.</description>
        <time_frame>28 days or 4 weeks (cycle 1)</time_frame>
        <population>This outcome measure was not done. The MTD was not found because the study was closed after &gt; 1 year of inactivity and only one participant was enrolled.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose (MTD) of Intravenous (IV) Obinutuzumab Treatment</title>
          <description>The MTD is the dose level at which no more than 1 of up to 6 participants experience a dose limiting toxicity (DLT) during the DLT evaluation window, or the dose at which at least 2 of ≤ 6 participants have DLT. A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to Obinutuzumab by the principal investigator during the first 28 days of treatment.</description>
          <population>This outcome measure was not done. The MTD was not found because the study was closed after &gt; 1 year of inactivity and only one participant was enrolled.</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>Duration of Response (DOR)</title>
        <description>DOR is measured from the time measurement criteria are met for complete response (CR), complete response with incomplete marrow recovery (CRi), or partial response (PR) whichever is recorded first until the first date that recurrent of progressive disease is objectively documented, death, or in the absence of progressive disease (PD), date of last assessment. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. Complete response (CR) is disease related constitutional symptoms resolved; partial response (PR) is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met; complete response with incomplete marrow recovery (CRi) is CR with incomplete hematopoietic recovery; stable disease (SD) is defined as not achieving CR or PR, and PD is development of transformation to a more aggressive histology.</description>
        <time_frame>time measurement criteria are met for CR, CRi, or PR whichever is recorded first until the first date that recurrent of progressive disease is objectively documented or death, approximately 27 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR)</title>
          <description>DOR is measured from the time measurement criteria are met for complete response (CR), complete response with incomplete marrow recovery (CRi), or partial response (PR) whichever is recorded first until the first date that recurrent of progressive disease is objectively documented, death, or in the absence of progressive disease (PD), date of last assessment. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. Complete response (CR) is disease related constitutional symptoms resolved; partial response (PR) is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met; complete response with incomplete marrow recovery (CRi) is CR with incomplete hematopoietic recovery; stable disease (SD) is defined as not achieving CR or PR, and PD is development of transformation to a more aggressive histology.</description>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="NA" upper_limit="NA">There is no confidence interval with 1 sample result.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate</title>
        <description>Overall response is defined as the best response recorded from the start of the treatment until disease progression/recurrence. OS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. Complete response (CR) is disease related constitutional symptoms resolved; Partial response (PR) is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met, requires the absence of growth factor or transfusion support; Complete response with incomplete marrow recovery (CRi) is CR with incomplete hematopoietic recovery; Stable disease (SD) is defined as not achieving CR or PR, but not fulfilling the criteria for progressive disease (PD); and PD is one criteria from Group A or B are met or development of transformation to a more aggressive histology.</description>
        <time_frame>6 cycles (each cycle is 28 days or 4 weeks)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate</title>
          <description>Overall response is defined as the best response recorded from the start of the treatment until disease progression/recurrence. OS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. Complete response (CR) is disease related constitutional symptoms resolved; Partial response (PR) is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met, requires the absence of growth factor or transfusion support; Complete response with incomplete marrow recovery (CRi) is CR with incomplete hematopoietic recovery; Stable disease (SD) is defined as not achieving CR or PR, but not fulfilling the criteria for progressive disease (PD); and PD is one criteria from Group A or B are met or development of transformation to a more aggressive histology.</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="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Complete Response with incomplete marrow recovery</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease</title>
              <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>Event-free Survival (EFS)</title>
        <description>EFS is defined as the duration of time from the date of study enrollment until time of disease lapse, disease progression, alternative therapy for lymphoma given, or death, whichever comes first. EFS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Progression was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines and is defined as one criterion from Group A (e.g., lymphadenopathy or liver and/or spleen size) or B (e.g., platelet count) are met or development of transformation to a more aggressive histology.</description>
        <time_frame>Approximately 8 months</time_frame>
        <population>There is no confidence interval with 1 sample result.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Event-free Survival (EFS)</title>
          <description>EFS is defined as the duration of time from the date of study enrollment until time of disease lapse, disease progression, alternative therapy for lymphoma given, or death, whichever comes first. EFS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Progression was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines and is defined as one criterion from Group A (e.g., lymphadenopathy or liver and/or spleen size) or B (e.g., platelet count) are met or development of transformation to a more aggressive histology.</description>
          <population>There is no confidence interval with 1 sample result.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS is defined as the date of on-study to the date of death from any cause or last follow up.</description>
        <time_frame>Approximately 27 months</time_frame>
        <population>There is no full range with 1 sample result.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS is defined as the date of on-study to the date of death from any cause or last follow up.</description>
          <population>There is no full range with 1 sample result.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>PFS is defined as the duration of time measurement criteria are met for complete response (CR), complete response with incomplete marrow recovery (CRi), and partial response (PR), whichever is recorded first. PFS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. CR is disease related constitutional symptoms resolved; PR is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met, requires the absence of growth factor or transfusion support; CRi is CR with incomplete hematopoietic recovery; and progressive disease is one criteria from Group A or B are met or development of transformation to a more aggressive histology.</description>
        <time_frame>Approximately 8 months</time_frame>
        <population>There is no full range with 1 sample result.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>PFS is defined as the duration of time measurement criteria are met for complete response (CR), complete response with incomplete marrow recovery (CRi), and partial response (PR), whichever is recorded first. PFS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. CR is disease related constitutional symptoms resolved; PR is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met, requires the absence of growth factor or transfusion support; CRi is CR with incomplete hematopoietic recovery; and progressive disease is one criteria from Group A or B are met or development of transformation to a more aggressive histology.</description>
          <population>There is no full range with 1 sample result.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).</title>
        <description>Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
        <time_frame>Date treatment consent signed to date off study, approximately 27 months and 11 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1 - Dose Escalation - Dose Level 1</title>
            <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).</title>
          <description>Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</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="1"/>
              </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_list>

    <reported_events>
      <time_frame>Date treatment consent signed to date off study, approximately 27 months and 11 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm 1 - Dose Escalation - Dose Level 1</title>
          <description>Each cycle of treatment is 28 days or 4 weeks, and a maximum of 6 cycles will be administered.&#xD;
Participant was treated with continuous intravenous (civ) interleukin-15 (IL-15) on dose level 1 with 0.5 mcg/kg/day on days 1-5 of cycles 1-6.&#xD;
Obinutuzumab (IV) will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <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="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bone infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculopapular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (5.0)</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="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </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="1"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </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="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>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. Kevin Conlon</name_or_title>
      <organization>National Cancer Institute</organization>
      <phone>240-858-3570</phone>
      <email>conlonkc@mail.nih.gov</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/NCT03759184
org study id: 190024
secondary id: 19-C-0024
nct id: NCT03759184
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Background:

      Chronic lymphocytic leukemia (CLL) is a blood cancer. Recombinant human interleukin 15
      (IL-15) is a manmade protein. Obinutuzumab is a protein made to deactivate cancer cells.
      Researchers want to see if treating people with CLL with both proteins improves their
      outcomes.

      Objectives:

      To find the safe dose of IL-15 with Obinutuzumab. To identify its effects, including on the
      immune system and cancer.

      Eligibility:

      Adults at least 18 years old who have certain CLL that standard therapy has failed

      Design:

      Participants will be screened with:

        -  Medical history

        -  Physical exam

        -  Evaluation of ability to do daily activities

        -  Blood, heart, and urine tests

      Participants may also be screened with:

        -  A small amount of bone marrow removed by needle in the hipbone

        -  Scans of the body and/or brain

      The study will be done in 28-day cycles for up to 6 cycles.

      Participants will get the study drugs through a catheter and pump.

      Cycle 1: Participants will be seen in the clinic during week 1. They will get:

        -  IL-15 as a continuous intravenous infusion over 24 hours on days 1-5 and 3 dose levels
           will be evaluated: dose level 1; 0.5 mcg/kg/day; dose level 2: 1 mcg/kg/day and dose
           level 3: 2 mcg/kg/day.

        -  Obinutuzumab as a 4-hour infusion in escalating doses during the course of the first
           cycle 100 mg on day 4, 900 mg on day 5, 1000 mg on day 11 and day 18.

      Cycles 2 through 6: Participants will come to the clinic days 1-5 and get IL-15 as in cycle 1
      and Obinutuzumab 1000 mg on day 4 of each treatment cycle.

      During the study, participants:

        -  Will repeat screening tests

        -  Will get standard medicines for side effects

        -  May give blood, saliva, and tumor samples for research

      After treatment, participants will have follow-up visits every 3 months for 1 year, then
      every 6 months for up to 5 years. After that, participants may be called or emailed.
Background:

        -  Of the several drugs and drug combinations approved for treatment of relapsed and
           refractory chronic lymphocytic leukemia (CLL), the reported complete response rates are
           no greater than 30%.

        -  Obinutuzumab is a glycoengineered, humanized type 2 anti-cluster of differentiation 20
           (CD20) monoclonal antibody thought to engage the immune system by directly activating
           antibody-dependent, cell mediated cytotoxicity (ADCC); it is approved for treatment of
           chronic lymphocytic leukemia in combination with chlorambucil.

        -  The key mediators of ADCC are polymorphonuclear neutrophils, monocytes, and natural
           killer (NK) cells.

        -  Recombinant human Interleukin-15 (rhIL-15) is a stimulatory cytokine that promotes the
           differentiation and activation of NK cells, monocytes, and long-term cluster of
           differentiation 8 (CD8) + memory T-cells. In a Phase I trial, administration of rhIL-15
           as a 5-day continuous intravenous infusion (civ) was associated with up to 45-fold
           increase in the number of NK cells at well tolerated dose levels.

        -  Preclinical murine lymphoid malignancy models have shown increased efficacy of
           monoclonal antibodies when administered together with recombinant human Interleukin-15
           (rhIL-15); BL/6 mice inoculated with EL4 murine T-cell lymphoma expressing human cluster
           of differentiation 20 (EL4-CD20) cells (a syngeneic lymphoma line); including
           significant prolongation of survival with the IL-15/Rituximab combination compared to
           either drug given as single agent (90% v. 30% alive at 75 days).

      Objectives:

      - To determine the safety, toxicity profile, dose-limiting toxicity (DLT) and the maximum
      tolerated dose (MTD) of civ rhIL-15 administration in combination with intravenous (IV)
      Obinutuzumab treatment

      Eligibility:

        -  Age greater than or equal to 18 years old

        -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1

        -  Diagnosis of chronic lymphocytic leukemia (CLL) with greater than or equal to 50% of B
           cells expressing CD20

        -  Patients must have measurable or evaluable disease

        -  Patients must have CLL that is refractory or relapsed following therapy with a Bruton's
           tyrosine kinase (BTK) inhibitor OR have relapsed/refractory CLL and are intolerant to
           BTK inhibitor therapy; patients with deletion 17p (del(17p) must also be refractory or
           relapsed after, or intolerant to, therapy with Venetoclax

        -  Adequate organ function parameters as defined within the protocol

        -  Active disease requiring treatment, as defined within the protocol

      Design:

        -  This is a single institution non-randomized Phase I dose escalation study evaluating
           increasing doses of civ rhIL-15 in combination with Obinutuzumab using a standard 3 + 3
           dose escalation design.

        -  On days 1-5 of each 4-week cycle, rhIL-15 will be administered by civ at dose levels
           0.5, 1, and 2 mcg/kg/day.

        -  During the first cycle, Obinutuzumab will be administered at a dose of 100 mg by IV on
           day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18: then 1,000 mg on day
           4 of each subsequent cycle.

        -  Infusion reaction, antimicrobial, and tumor lysis syndrome prophylaxis will be
           administered per manufacturers recommendations.

        -  Treatment will continue up to 6 cycles, or until unacceptable toxicity or progressive
           disease.

        -  Up to 24 patients will be enrolled in the study.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Treatment-emergent Adverse Events (AEs) Related to Recombinant Human Interleukin-15 (rhIL-15)
time frame: 28 days or 4 weeks (cycle 1)
description: Here is the number of treatment-emergent AEs related to rhIL-15 assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A treatment emergent AE is defined as
measure: Number of Treatment-emergent Adverse Events (AEs) Related to Obinutuzumab
time frame: 28 days or 4 weeks (cycle 1)
description: Here is the number of treatment-emergent AEs related to Obinutuzumab assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A treatment emergent AE is defined as
measure: Number of Participants With a Grades 3-5 Dose-limiting Toxicity (DLT) of Continuous Intravenous (CIV) Recombinant Human Interleukin-15 (rhIL-15) Treatment
time frame: 28 days or 4 weeks (cycle 1)
description: A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to interleukin-15 by the principal investigator during the first 28 days of treatment. Some exceptions are grade 3 or 4 lymphocytopenia or neutropenia without clinical signs of infection grade 2 or above, grade 3 or 4 thrombocytopenia lasting fewer than 5 days and not associated with bleeding or purpura. Transient (<24 hours) grade 3 hypoalbuminemia, hypokalemia, hypomagnesemia, hyponatremia or hypophosphatemia which responds to medical intervention. Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.
measure: Number of Participants With a Grade 3-5 Dose-limiting Toxicity (DLT) With Intravenous (IV) Obinutuzumab Treatment
time frame: 28 days or 4 weeks (cycle 1)
description: A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to Obinutuzumab by the principal investigator during the first 28 days of treatment. Some exceptions are grade 3 or 4 lymphocytopenia or neutropenia without clinical signs of infection grade 2 or above, grade 3 or 4 thrombocytopenia lasting fewer than 5 days and not associated with bleeding or purpura. Transient (<24 hours) grade 3 hypoalbuminemia, hypokalemia, hypomagnesemia, hyponatremia or hypophosphatemia which responds to medical intervention. Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.
measure: Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) Administration
time frame: 28 days or 4 weeks (cycle 1)
description: The MTD is the dose level at which no more than 1 of up to 6 participants experience a dose limiting toxicity (DLT) during the DLT evaluation window, or the dose at which at least 2 of ≤ 6 participants have DLT. A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to interleukin-15 by the principal investigator during the first 28 days of treatment.
measure: Maximum Tolerated Dose (MTD) of Intravenous (IV) Obinutuzumab Treatment
time frame: 28 days or 4 weeks (cycle 1)
description: The MTD is the dose level at which no more than 1 of up to 6 participants experience a dose limiting toxicity (DLT) during the DLT evaluation window, or the dose at which at least 2 of ≤ 6 participants have DLT. A DLT is defined as a grade 3-5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably, or definitely related to Obinutuzumab by the principal investigator during the first 28 days of treatment.
measure: Duration of Response (DOR)
time frame: time measurement criteria are met for CR, CRi, or PR whichever is recorded first until the first date that recurrent of progressive disease is objectively documented or death, approximately 27 months
description: DOR is measured from the time measurement criteria are met for complete response (CR), complete response with incomplete marrow recovery (CRi), or partial response (PR) whichever is recorded first until the first date that recurrent of progressive disease is objectively documented, death, or in the absence of progressive disease (PD), date of last assessment. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. Complete response (CR) is disease related constitutional symptoms resolved; partial response (PR) is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met; complete response with incomplete marrow recovery (CRi) is CR with incomplete hematopoietic recovery; stable disease (SD) is defined as not achieving CR or PR, and PD is development of transformation to a more aggressive histology.
measure: Overall Response Rate
time frame: 6 cycles (each cycle is 28 days or 4 weeks)
description: Overall response is defined as the best response recorded from the start of the treatment until disease progression/recurrence. OS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. Complete response (CR) is disease related constitutional symptoms resolved; Partial response (PR) is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met, requires the absence of growth factor or transfusion support; Complete response with incomplete marrow recovery (CRi) is CR with incomplete hematopoietic recovery; Stable disease (SD) is defined as not achieving CR or PR, but not fulfilling the criteria for progressive disease (PD); and PD is one criteria from Group A or B are met or development of transformation to a more aggressive histology.
measure: Event-free Survival (EFS)
time frame: Approximately 8 months
description: EFS is defined as the duration of time from the date of study enrollment until time of disease lapse, disease progression, alternative therapy for lymphoma given, or death, whichever comes first. EFS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Progression was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines and is defined as one criterion from Group A (e.g., lymphadenopathy or liver and/or spleen size) or B (e.g., platelet count) are met or development of transformation to a more aggressive histology.
measure: Overall Survival (OS)
time frame: Approximately 27 months
description: OS is defined as the date of on-study to the date of death from any cause or last follow up.
measure: Progression-free Survival (PFS)
time frame: Approximately 8 months
description: PFS is defined as the duration of time measurement criteria are met for complete response (CR), complete response with incomplete marrow recovery (CRi), and partial response (PR), whichever is recorded first. PFS was estimated using the Kaplan-Meier curves and a 95% confidence interval. Response was assessed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. CR is disease related constitutional symptoms resolved; PR is two criteria from Group A (e.g. lymphadenopathy or liver and/or spleen size) if abnormal at baseline plus one of the criteria from Group B (e.g. platelet count) must be met, requires the absence of growth factor or transfusion support; CRi is CR with incomplete hematopoietic recovery; and progressive disease is one criteria from Group A or B are met or development of transformation to a more aggressive histology.
measure: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
time frame: Date treatment consent signed to date off study, approximately 27 months and 11 days.
description: Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
arm group label: Arm 1 -DOSE ESCALATION
arm group type: Experimental
description: DOSE ESCALATION: Interleukin-15 (IL-15) by continuous intravenous (civ) infusion at escalating doses of 0.5, 1, and 2 mcg/kg/day on days 1-5 of each 4-week cycle (max 6 cycles), with Obinutuzumab by IV infusion at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of the first cycle; then 1,000 mg on day 4 of each subsequent cycle, to determine the maximum tolerated dose (MTD)
arm group label: Arm 2 - DOSE EXPANSION
arm group type: Experimental
description: DOSE EXPANSION: 3 to 6 patients to receive interleukin-15 (IL-15) by continuous intravenous (civ) infusion at the maximum tolerated dose (MTD) on days 1-5 of cycles 1-6 with Obinutuzumab by IV infusion at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of the first cycle; then 1,000 mg on day 4 of each subsequent cycle (Total 9 patients at MTD)
intervention type: Drug
intervention name: rhIL-15
description: Continuous intravenous (civ) Interleukin-15 (IL-15) at dose levels of 0.5,1 or 2 mcg/kg/day on days 1-5 of cycles 1-6
arm group label: Arm 1 -DOSE ESCALATION
other name: Recombinant human interleukin-15
intervention type: Drug
intervention name: rhIL-15
description: Continuous intravenous (civ) Interleukin-15 (IL-15) at the maximum tolerated dose or the maximum administered dose of 2 mcg/kg/day on days 1-5 of cycles 1-6
arm group label: Arm 2 - DOSE EXPANSION
other name: Recombinant human interleukin-15
intervention type: Biological
intervention name: Obinutuzumab
description: Intravenous (IV) Obinutuzumab will be administered at a dose of 100 mg on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18 of cycle 1: then 1,000 mg on day 4 of each subsequent cycle
arm group label: Arm 1 -DOSE ESCALATION
arm group label: Arm 2 - DOSE EXPANSION
other name: Gazyva
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kevin C Conlon, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2019-C-0024.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Principal Investigator
investigator affiliation: National Cancer Institute (NCI)
investigator full name: Kevin Conlon, MD
investigator title: Principal Investigator
mesh term: Leukemia
mesh term: Obinutuzumab
sharing ipd: Yes
ipd description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genome Data Sharing (GDS) plan for as long as database is active.
ipd access criteria: Clinical data will be made available via subscription to Biomedical Translational Research (BTRIS) and with the permission of the study principal investigator (PI).
Genomic data are made available via database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 