<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/NCT02225275</url>
  </required_header>
  <id_info>
    <org_study_id>2014-0115</org_study_id>
    <secondary_id>NCI-2015-00237</secondary_id>
    <secondary_id>2014-0115</secondary_id>
    <nct_id>NCT02225275</nct_id>
  </id_info>
  <brief_title>Lenalidomide and Obinutuzumab in Treating Patients With Recurrent or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma</brief_title>
  <official_title>Combination of Lenalidomide and Obinutuzumab (GA101) in Patients With Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</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>
      This phase II trial studies how well lenalidomide and obinutuzumab work in treating patients&#xD;
      with chronic lymphocytic leukemia or small lymphocytic lymphoma that has come back&#xD;
      (recurrent) or does not respond to treatment (refractory). Drugs used in chemotherapy, such&#xD;
      as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing&#xD;
      the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal&#xD;
      antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and&#xD;
      spread. Giving lenalidomide and obinutuzumab may work better in treating patients with&#xD;
      chronic lymphocytic leukemia or small lymphocytic lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Overall response defined as achievement of complete response (CR) or partial response&#xD;
      (PR).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Safety of the combination. II. Response according to prognostic markers at diagnosis. III.&#xD;
      Time to next treatment. IV. Overall survival.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive obinutuzumab intravenously (IV) over 3-4 hours on days 1, 2, 8, and 15 of&#xD;
      course 1 and day 1 of courses 2-6 and lenalidomide orally (PO) once daily (QD) on days 9-28&#xD;
      of course 1 and days 1-28 of all subsequent courses. Treatment repeats every 28 days for up&#xD;
      to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may&#xD;
      continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to slow accrual&#xD;
  </why_stopped>
  <start_date type="Actual">March 31, 2016</start_date>
  <completion_date type="Actual">May 19, 2021</completion_date>
  <primary_completion_date type="Actual">May 19, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With a Response</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Response is Complete Response or Partial Response. CR is absence of Lymphadenopathy, Hepatomegaly or Splenomegaly, lymphocytes &lt; 4000/ul, normocellular, &lt;30% lymphocytes, no B-lymphoid nodules, Platelets &gt; 100,000/ul, hemoglobin &gt;11.0 g/dl and Neutrophils &gt;1500/ul.&#xD;
PR is &gt;/= 50% decrease in lymphadenopathy, hepatomegaly, splenomegaly and Blood Lymphocytes from baseline, 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count &gt; 100,000/ul, Hemoglobin &gt; 11 g/dl and Neutrophils &gt;1500/ul or increase &gt;/= 50% of all over base.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Next Treatment</measure>
    <time_frame>Up to 5 years, 2 months</time_frame>
    <description>The time-to-event outcomes (such as time to next treatment or overall survival). Time to Next Treatment is from start of study medication to the start of the next treatment, or last follow up if no next therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 5 years, 2 months</time_frame>
    <description>Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Recurrent Chronic Lymphocytic Leukemia</condition>
  <condition>Recurrent Small Lymphocytic Lymphoma</condition>
  <condition>Refractory Chronic Lymphocytic Leukemia</condition>
  <condition>Refractory Small Lymphocytic Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (lenalidomide, obinutuzumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive obinutuzumab IV over 3-4 hours on days 1, 2, 8, and 15 of course 1 and day 1 of courses 2-6 and lenalidomide PO QD on days 9-28 of course 1 and days 1-28 of all subsequent courses. Treatment with obinutuzumab repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (lenalidomide, obinutuzumab)</arm_group_label>
    <other_name>CC-5013</other_name>
    <other_name>CC5013</other_name>
    <other_name>CDC 501</other_name>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Obinutuzumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (lenalidomide, obinutuzumab)</arm_group_label>
    <other_name>Anti-CD20 Monoclonal Antibody R7159</other_name>
    <other_name>GA-101</other_name>
    <other_name>GA101</other_name>
    <other_name>Gazyva</other_name>
    <other_name>huMAB(CD20)</other_name>
    <other_name>R7159</other_name>
    <other_name>RO 5072759</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to understand and to provide voluntarily informed consent&#xD;
&#xD;
          -  Have documented chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)&#xD;
             according to National Cancer Institute (NCI) criteria&#xD;
&#xD;
          -  Recurrent or refractory disease according to NCI criteria&#xD;
&#xD;
          -  Patient are eligible if they have received one or more prior treatment&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2&#xD;
&#xD;
          -  Life expectancy &gt; 6 months&#xD;
&#xD;
          -  Serum creatinine less or equal to 2 mg/dl&#xD;
&#xD;
          -  Total bilirubin less or equal to 2 mg/dl&#xD;
&#xD;
          -  Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) less or&#xD;
             equal to two times the upper normal limit&#xD;
&#xD;
          -  Disease free of prior malignancies for 3 years with exception of currently treated&#xD;
             basal cell squamous cell carcinoma of the skin, or carcinoma &quot;in situ&quot; of the cervix&#xD;
             or breast; patients with malignancies with indolent behavior such as prostate cancer&#xD;
             treated with radiation or surgery can be enrolled in the study as long as they have a&#xD;
             reasonable expectation to have been cured with the treatment modality received&#xD;
&#xD;
          -  No prior history of myelodysplastic syndrome or other myeloid malignancy&#xD;
&#xD;
          -  All participants must be registered into the mandatory Revlimid Risk Evaluation and&#xD;
             Mitigation Strategy (REMS) program, and be willing and able to comply with the&#xD;
             requirements of the Revlimid REMS&#xD;
&#xD;
          -  Females of childbearing potential (FCBP) must have a negative serum and/or urine&#xD;
             pregnancy test with a sensitive of at least 50 mIU/mL within 10-14 days and again&#xD;
             within 24 hours prior to prescribe lenalidomide for cycle 1 (prescriptions must be&#xD;
             filled within 7 days as required by Revlimid REMS) and must either commit to continued&#xD;
             abstinence from heterosexual intercourse or begin TWO acceptable methods of birth&#xD;
             control, one highly effective method and one additional effective method AT THE SAME&#xD;
             TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to&#xD;
             ongoing pregnancy testing; men must agree to use a latex condom during sexual contact&#xD;
             with a FCBP even if they have had a successful vasectomy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known sensitivity to lenalidomide or other thalidomide derivatives or anti cluster of&#xD;
             differentiation (CD)20&#xD;
&#xD;
          -  Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood)&#xD;
&#xD;
          -  Known history of infection with human immunodeficiency virus (HIV) or human T cell&#xD;
             leukemia virus 1 (HTLV-1)&#xD;
&#xD;
          -  Serologic status reflecting active hepatitis B or C; patients with hepatitis B (HBV)&#xD;
             antibody positive but who have positivity for hepatitis B surface antigen (HBsAg) or&#xD;
             anti hepatitis B core antibody (anti-HBc) and patients who are positive for&#xD;
             anti-hepatitis C (HCV) will need to have a negative polymerase chain reaction (PCR)&#xD;
             (viral HBV deoxyribonucleic acid [DNA] or HCV ribonucleic acid [RNA]) result prior to&#xD;
             enrollment; those who are HBsAg positive or HBV DNA positive and those who are&#xD;
             positive for HCV (RNA) will be excluded&#xD;
&#xD;
          -  Pregnant or breast feeding females&#xD;
&#xD;
          -  History of tuberculosis treated within the last five years or recent exposure to&#xD;
             tuberculosis&#xD;
&#xD;
          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that&#xD;
             places the subject unacceptable risk if he/she were to participate to the study&#xD;
&#xD;
          -  Patients with a recent history of deep vein thrombosis or pulmonary embolus, in the&#xD;
             six months prior to enrollment are not eligible for this study&#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>Alessandra Ferrajoli</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 22, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <results_first_submitted>May 17, 2022</results_first_submitted>
  <results_first_submitted_qc>September 13, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 28, 2022</results_first_posted>
  <last_update_submitted>September 13, 2022</last_update_submitted>
  <last_update_submitted_qc>September 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Obinutuzumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 29, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/75/NCT02225275/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment Period: March 2016 to May 2021</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Lenalidomide, Obinutuzumab)</title>
          <description>Patients receive obinutuzumab IV over 3-4 hours on days 1, 2, 8, and 15 of course 1 and day 1 of courses 2-6 and lenalidomide PO QD on days 9-28 of course 1 and days 1-28 of all subsequent courses. Treatment with obinutuzumab repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Lenalidomide: Given PO&#xD;
Obinutuzumab: Given IV</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Lenalidomide, Obinutuzumab)</title>
          <description>Patients receive obinutuzumab IV over 3-4 hours on days 1, 2, 8, and 15 of course 1 and day 1 of courses 2-6 and lenalidomide PO QD on days 9-28 of course 1 and days 1-28 of all subsequent courses. Treatment with obinutuzumab repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Lenalidomide: Given PO&#xD;
Obinutuzumab: Given IV</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69" lower_limit="60" upper_limit="79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With a Response</title>
        <description>Response is Complete Response or Partial Response. CR is absence of Lymphadenopathy, Hepatomegaly or Splenomegaly, lymphocytes &lt; 4000/ul, normocellular, &lt;30% lymphocytes, no B-lymphoid nodules, Platelets &gt; 100,000/ul, hemoglobin &gt;11.0 g/dl and Neutrophils &gt;1500/ul.&#xD;
PR is &gt;/= 50% decrease in lymphadenopathy, hepatomegaly, splenomegaly and Blood Lymphocytes from baseline, 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count &gt; 100,000/ul, Hemoglobin &gt; 11 g/dl and Neutrophils &gt;1500/ul or increase &gt;/= 50% of all over base.</description>
        <time_frame>Up to 5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Lenalidomide, Obinutuzumab)</title>
            <description>Patients receive obinutuzumab IV over 3-4 hours on days 1, 2, 8, and 15 of course 1 and day 1 of courses 2-6 and lenalidomide PO QD on days 9-28 of course 1 and days 1-28 of all subsequent courses. Treatment with obinutuzumab repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Lenalidomide: Given PO&#xD;
Obinutuzumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Response</title>
          <description>Response is Complete Response or Partial Response. CR is absence of Lymphadenopathy, Hepatomegaly or Splenomegaly, lymphocytes &lt; 4000/ul, normocellular, &lt;30% lymphocytes, no B-lymphoid nodules, Platelets &gt; 100,000/ul, hemoglobin &gt;11.0 g/dl and Neutrophils &gt;1500/ul.&#xD;
PR is &gt;/= 50% decrease in lymphadenopathy, hepatomegaly, splenomegaly and Blood Lymphocytes from baseline, 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count &gt; 100,000/ul, Hemoglobin &gt; 11 g/dl and Neutrophils &gt;1500/ul or increase &gt;/= 50% of all over base.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Next Treatment</title>
        <description>The time-to-event outcomes (such as time to next treatment or overall survival). Time to Next Treatment is from start of study medication to the start of the next treatment, or last follow up if no next therapy.</description>
        <time_frame>Up to 5 years, 2 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Lenalidomide, Obinutuzumab)</title>
            <description>Patients receive obinutuzumab IV over 3-4 hours on days 1, 2, 8, and 15 of course 1 and day 1 of courses 2-6 and lenalidomide PO QD on days 9-28 of course 1 and days 1-28 of all subsequent courses. Treatment with obinutuzumab repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Lenalidomide: Given PO&#xD;
Obinutuzumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Next Treatment</title>
          <description>The time-to-event outcomes (such as time to next treatment or overall survival). Time to Next Treatment is from start of study medication to the start of the next treatment, or last follow up if no next therapy.</description>
          <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="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.9" lower_limit="2.7" upper_limit="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis.</description>
        <time_frame>Up to 5 years, 2 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Lenalidomide, Obinutuzumab)</title>
            <description>Patients receive obinutuzumab IV over 3-4 hours on days 1, 2, 8, and 15 of course 1 and day 1 of courses 2-6 and lenalidomide PO QD on days 9-28 of course 1 and days 1-28 of all subsequent courses. Treatment with obinutuzumab repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Lenalidomide: Given PO&#xD;
Obinutuzumab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis.</description>
          <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="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="2.7" upper_limit="62">Median not reached due to insufficient number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 5 years, 2 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Lenalidomide, Obinutuzumab)</title>
          <description>Patients receive obinutuzumab IV over 3-4 hours on days 1, 2, 8, and 15 of course 1 and day 1 of courses 2-6 and lenalidomide PO QD on days 9-28 of course 1 and days 1-28 of all subsequent courses. Treatment with obinutuzumab repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Lenalidomide: Given PO&#xD;
Obinutuzumab: Given IV</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</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="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</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="9" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Lymph Node Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear Inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Sclera Disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Uveitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastroesophageal Reflux Disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Skin Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion Related Reaction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminiotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Alkaline Phosphatase Increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="19" subjects_affected="7" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomina</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash Maculo-papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Thromboembolic Event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Alessandra Ferrajoli MD/ Professor</name_or_title>
      <organization>The University of Texas MD Anderson Cancer Center</organization>
      <phone>173-792-2063</phone>
      <email>aferrajo@mdanderson.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02225275
org study id: 2014-0115
secondary id: NCI-2015-00237
secondary id: 2014-0115
nct id: NCT02225275
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well lenalidomide and obinutuzumab work in treating patients
      with chronic lymphocytic leukemia or small lymphocytic lymphoma that has come back
      (recurrent) or does not respond to treatment (refractory). Drugs used in chemotherapy, such
      as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing
      the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal
      antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and
      spread. Giving lenalidomide and obinutuzumab may work better in treating patients with
      chronic lymphocytic leukemia or small lymphocytic lymphoma.
PRIMARY OBJECTIVES:

      I. Overall response defined as achievement of complete response (CR) or partial response
      (PR).

      SECONDARY OBJECTIVES:

      I. Safety of the combination. II. Response according to prognostic markers at diagnosis. III.
      Time to next treatment. IV. Overall survival.

      OUTLINE:

      Patients receive obinutuzumab intravenously (IV) over 3-4 hours on days 1, 2, 8, and 15 of
      course 1 and day 1 of courses 2-6 and lenalidomide orally (PO) once daily (QD) on days 9-28
      of course 1 and days 1-28 of all subsequent courses. Treatment repeats every 28 days for up
      to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may
      continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable
      toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With a Response
time frame: Up to 5 years
description: Response is Complete Response or Partial Response. CR is absence of Lymphadenopathy, Hepatomegaly or Splenomegaly, lymphocytes < 4000/ul, normocellular, <30% lymphocytes, no B-lymphoid nodules, Platelets > 100,000/ul, hemoglobin >11.0 g/dl and Neutrophils >1500/ul.
PR is >/= 50% decrease in lymphadenopathy, hepatomegaly, splenomegaly and Blood Lymphocytes from baseline, 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count > 100,000/ul, Hemoglobin > 11 g/dl and Neutrophils >1500/ul or increase >/= 50% of all over base.
measure: Time to Next Treatment
time frame: Up to 5 years, 2 months
description: The time-to-event outcomes (such as time to next treatment or overall survival). Time to Next Treatment is from start of study medication to the start of the next treatment, or last follow up if no next therapy.
measure: Overall Survival
time frame: Up to 5 years, 2 months
description: Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis.
arm group label: Treatment (lenalidomide, obinutuzumab)
arm group type: Experimental
description: Patients receive obinutuzumab IV over 3-4 hours on days 1, 2, 8, and 15 of course 1 and day 1 of courses 2-6 and lenalidomide PO QD on days 9-28 of course 1 and days 1-28 of all subsequent courses. Treatment with obinutuzumab repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Lenalidomide
description: Given PO
arm group label: Treatment (lenalidomide, obinutuzumab)
other name: CC-5013
other name: CC5013
other name: CDC 501
other name: Revlimid
intervention type: Biological
intervention name: Obinutuzumab
description: Given IV
arm group label: Treatment (lenalidomide, obinutuzumab)
other name: Anti-CD20 Monoclonal Antibody R7159
other name: GA-101
other name: GA101
other name: Gazyva
other name: huMAB(CD20)
other name: R7159
other name: RO 5072759
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alessandra Ferrajoli
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Recurrence
mesh term: Lenalidomide
mesh term: Obinutuzumab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 