<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/NCT01682044</url>
  </required_header>
  <id_info>
    <org_study_id>I 83106</org_study_id>
    <secondary_id>NCI-2011-00134</secondary_id>
    <nct_id>NCT01682044</nct_id>
    <nct_alias>NCT00524628</nct_alias>
  </id_info>
  <brief_title>Pegfilgrastim and Rituximab in Treating Patients With Untreated, Relapsed, or Refractory Follicular Lymphoma, Small Lymphocytic Lymphoma, or Marginal Zone Lymphoma</brief_title>
  <official_title>Phase II Clinical Trial of Rituximab in Combination With Pegfilgrastim in Patients With Indolent B-Cell (CD-20-Positive) Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Roswell Park Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Roswell Park Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies the side effects and how well giving pegfilgrastim together with&#xD;
      rituximab works in treating patients with untreated, relapsed, or refractory follicular&#xD;
      lymphoma, small lymphocytic lymphoma (SLL), or marginal zone lymphoma (MZL).&#xD;
      Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells&#xD;
      found in bone marrow or peripheral blood and may help the immune system recover from the side&#xD;
      effects of therapy. Monoclonal antibodies, such as rituximab, can block cancer growth in&#xD;
      different ways. Some block the ability of cancer to grow and spread. Others find cancer cells&#xD;
      and help kill them or tumor cancer-killing substances to them. Giving pegfilgrastim together&#xD;
      with rituximab may kill more cancer cells&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the safety of Pegfilgrastim in combination with rituximab in patients with&#xD;
      untreated or relapsed/refractory follicular, SLL or MZL.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the efficacy (including overall response rate and durability of objective&#xD;
      responses) of Pegfilgrastim in combination with rituximab in patients with untreated or&#xD;
      relapsed/refractory follicular, SLL or MZL.&#xD;
&#xD;
      II. To evaluate functional and phenotypic characteristics of host neutrophils undergoing&#xD;
      treatment with Pegfilgrastim and rituximab.&#xD;
&#xD;
      III. To evaluate changes in cluster of differentiation (CD)20 antigen expression and density&#xD;
      of expression in patients receiving Pegfilgrastim and rituximab.&#xD;
&#xD;
      IV. To evaluate changes in serum levels of tumor necrosis factor (TNF), interferon alpha&#xD;
      (INFalpha) and free radical levels in patients undergoing treatment with Pegfilgrastim and&#xD;
      rituximab.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive pegfilgrastim subcutaneously (SC) followed by rituximab intravenously (IV) 3&#xD;
      days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of&#xD;
      disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 4 months for 1 year,&#xD;
      every 6 months for 2 years, and then yearly for 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 17, 2007</start_date>
  <completion_date type="Actual">December 22, 2016</completion_date>
  <primary_completion_date type="Actual">November 22, 2013</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 Adverse Events</measure>
    <time_frame>Up to 90 days after the last dose of study drugs</time_frame>
    <description>Frequency of Adverse Events, Graded According to NCI CTCAE v3.0. Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>Up to 43 weeks</time_frame>
    <description>Overall Response is defined as Complete Response: During observation, no disease is apparent, including measurable and non-measurable disease, and no evidence of disease is observed for at least 28 days, as confirmed by a second assessment following the original observation of no disease; and Partial Response: A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the 50% or greater decrease, and no appearance of new lesions is noted.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline</measure>
    <time_frame>Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39</time_frame>
    <description>Mean percent change in CD11b level from baseline at each visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in CD20 Antigen Expression and Density of Expression</measure>
    <time_frame>At 4 years</time_frame>
    <description>Percent change in CD20 antigen expression and density of expression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline</measure>
    <time_frame>Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39</time_frame>
    <description>Mean percent change in TNF level from baseline at each visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline</measure>
    <time_frame>Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39</time_frame>
    <description>Mean percent change in INF level from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline</measure>
    <time_frame>Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39</time_frame>
    <description>Mean percent change in MFI level from baseline.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Contiguous Stage II Grade 1 Follicular Lymphoma</condition>
  <condition>Contiguous Stage II Grade 2 Follicular Lymphoma</condition>
  <condition>Contiguous Stage II Grade 3 Follicular Lymphoma</condition>
  <condition>Contiguous Stage II Marginal Zone Lymphoma</condition>
  <condition>Contiguous Stage II Small Lymphocytic Lymphoma</condition>
  <condition>Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue</condition>
  <condition>Nodal Marginal Zone B-cell Lymphoma</condition>
  <condition>Noncontiguous Stage II Grade 1 Follicular Lymphoma</condition>
  <condition>Noncontiguous Stage II Grade 2 Follicular Lymphoma</condition>
  <condition>Noncontiguous Stage II Grade 3 Follicular Lymphoma</condition>
  <condition>Noncontiguous Stage II Marginal Zone Lymphoma</condition>
  <condition>Noncontiguous Stage II Small Lymphocytic Lymphoma</condition>
  <condition>Recurrent Grade 1 Follicular Lymphoma</condition>
  <condition>Recurrent Grade 2 Follicular Lymphoma</condition>
  <condition>Recurrent Grade 3 Follicular Lymphoma</condition>
  <condition>Recurrent Marginal Zone Lymphoma</condition>
  <condition>Recurrent Small Lymphocytic Lymphoma</condition>
  <condition>Splenic Marginal Zone Lymphoma</condition>
  <condition>Stage I Grade 1 Follicular Lymphoma</condition>
  <condition>Stage I Grade 2 Follicular Lymphoma</condition>
  <condition>Stage I Grade 3 Follicular Lymphoma</condition>
  <condition>Stage I Marginal Zone Lymphoma</condition>
  <condition>Stage I Small Lymphocytic Lymphoma</condition>
  <condition>Stage III Grade 1 Follicular Lymphoma</condition>
  <condition>Stage III Grade 2 Follicular Lymphoma</condition>
  <condition>Stage III Grade 3 Follicular Lymphoma</condition>
  <condition>Stage III Marginal Zone Lymphoma</condition>
  <condition>Stage III Small Lymphocytic Lymphoma</condition>
  <condition>Stage IV Grade 1 Follicular Lymphoma</condition>
  <condition>Stage IV Grade 2 Follicular Lymphoma</condition>
  <condition>Stage IV Grade 3 Follicular Lymphoma</condition>
  <condition>Stage IV Marginal Zone Lymphoma</condition>
  <condition>Stage IV Small Lymphocytic Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (colony-stimulating factor and monoclonal antibody)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pegfilgrastim</intervention_name>
    <description>Given SC</description>
    <arm_group_label>Treatment (colony-stimulating factor and monoclonal antibody)</arm_group_label>
    <other_name>Filgrastim SD-01</other_name>
    <other_name>GCSF-SD01</other_name>
    <other_name>Neulasta</other_name>
    <other_name>SD-01 sustained duration G-CSF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>rituximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (colony-stimulating factor and monoclonal antibody)</arm_group_label>
    <other_name>IDEC-C2B8</other_name>
    <other_name>IDEC-C2B8 monoclonal antibody</other_name>
    <other_name>Mabthera</other_name>
    <other_name>MOAB IDEC-C2B8</other_name>
    <other_name>Rituxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>flow cytometry</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (colony-stimulating factor and monoclonal antibody)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>biopsy</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (colony-stimulating factor and monoclonal antibody)</arm_group_label>
    <other_name>biopsies</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>immunohistochemistry staining method</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (colony-stimulating factor and monoclonal antibody)</arm_group_label>
    <other_name>immunohistochemistry</other_name>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>western blotting</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (colony-stimulating factor and monoclonal antibody)</arm_group_label>
    <other_name>Blotting, Western</other_name>
    <other_name>Western Blot</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Untreated or relapsed/refractory follicular, SLL or MZL (i.e. no limit to number of&#xD;
             prior treatments as long as patients meet other study criteria)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1&#xD;
&#xD;
          -  Measurable tumor size (at least one node measuring 4 cm^2 in bidimensional&#xD;
             measurement)&#xD;
&#xD;
          -  Expected survival of &gt; 6 months&#xD;
&#xD;
          -  Prior rituximab or other monoclonal immunotherapy permitted and eligible for rituximab&#xD;
             monotherapy&#xD;
&#xD;
          -  Full recovery from any significant toxicity associated with prior surgery, radiation&#xD;
             therapy, chemotherapy, or immunotherapy&#xD;
&#xD;
          -  Absolute neutrophil count &gt; 1.0 x 10^9/L&#xD;
&#xD;
          -  Platelets &gt; 50 x 10^9/L&#xD;
&#xD;
          -  Patients may receive erythropoietin growth factors to maintain adequate hemoglobin&#xD;
             levels (&gt;= 8.0 mg/dl)&#xD;
&#xD;
          -  Creatinine &lt; 1.5 x upper normal levels (UNL)&#xD;
&#xD;
          -  Total bilirubin &lt; 1.5 mg/dL (&gt; 25.65 umol/L)&#xD;
&#xD;
          -  Aspartate aminotransferase &lt; 5 x UNL&#xD;
&#xD;
          -  Alkaline phosphatase &lt; 5 x UNL&#xD;
&#xD;
          -  Informed consent approved in institutional review board (lRB)&#xD;
&#xD;
          -  CD20+ B-cell lymphoma&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior history of human immunodeficiency virus (HIV)-positivity (routine HIV testing is&#xD;
             required pretreatment)&#xD;
&#xD;
          -  Serious non-malignant disease (e.g. active uncontrolled bacterial, viral, or fungal&#xD;
             infections) or other conditions which, in the opinion of the principal investigator&#xD;
             would compromise other protocol objectives&#xD;
&#xD;
          -  Presence of central nervous system (CNS) lymphoma&#xD;
&#xD;
          -  Chemotherapy within 4 weeks of the first scheduled study treatment&#xD;
&#xD;
          -  Another primary malignancy (other than squamous or basal cell carcinoma of the skin or&#xD;
             in-situ carcinoma of the cervix) for which the patient has not been disease-free for&#xD;
             at least five years&#xD;
&#xD;
          -  Major surgery, other than diagnostic surgery, within four weeks&#xD;
&#xD;
          -  Patients with non-Hodgkin lymphoma (NHL) other than relapsed/refractory follicular,&#xD;
             MZL or SLL&#xD;
&#xD;
          -  Patients must not have a history of cardiac disease, defined as New York Heart&#xD;
             Association Class II or greater or clinical evidence of congestive heart failure&#xD;
&#xD;
          -  Concurrent use of other investigational agents&#xD;
&#xD;
          -  Pregnant or breast feeding&#xD;
&#xD;
          -  Subjects of reproductive potential who are not using adequate contraceptive&#xD;
             precautions, in the judgment of the investigator&#xD;
&#xD;
          -  Known hypersensitivity to any recombinant E coli-derived product, murine proteins, or&#xD;
             any components of the study medications&#xD;
&#xD;
          -  Concerns for the subject's compliance with the protocol&#xD;
&#xD;
          -  Any premalignant myeloid condition or any malignancy with myeloid characteristics&#xD;
             (e.g. myelodysplastic syndromes, acute or chronic myelogenous leukemia)&#xD;
&#xD;
          -  Patient is currently enrolled in, or has not yet completed at least 30 days since&#xD;
             ending another investigational device or drug trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francisco Hernandez-ILizaliturri</last_name>
    <role>Principal Investigator</role>
    <affiliation>Roswell Park Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 5, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <results_first_submitted>June 14, 2017</results_first_submitted>
  <results_first_submitted_qc>September 8, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">October 9, 2017</results_first_posted>
  <last_update_submitted>September 8, 2017</last_update_submitted>
  <last_update_submitted_qc>September 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 9, 2017</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>Lymphoma, Follicular</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, B-Cell, Marginal Zone</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>Rituximab</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>October 4, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT01682044/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Colony-stimulating Factor and Monoclonal Antibody)</title>
          <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
pegfilgrastim: Given SC&#xD;
rituximab: Given IV&#xD;
flow cytometry: Correlative studies&#xD;
biopsy: Correlative studies&#xD;
immunohistochemistry staining method: Correlative studies&#xD;
western blotting: Correlative studies</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progression</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All treated and eligible patients</population>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Colony-stimulating Factor and Monoclonal Antibody)</title>
          <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
pegfilgrastim: Given SC&#xD;
rituximab: Given IV&#xD;
flow cytometry: Correlative studies&#xD;
biopsy: Correlative studies&#xD;
immunohistochemistry staining method: Correlative studies&#xD;
western blotting: Correlative studies</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="60.9" spread="13.1"/>
                  </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Frequency of Adverse Events, Graded According to NCI CTCAE v3.0. Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE</description>
        <time_frame>Up to 90 days after the last dose of study drugs</time_frame>
        <population>All treated and eligible patients</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Colony-stimulating Factor and Monoclonal Antibody)</title>
            <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
pegfilgrastim: Given SC&#xD;
rituximab: Given IV&#xD;
flow cytometry: Correlative studies&#xD;
biopsy: Correlative studies&#xD;
immunohistochemistry staining method: Correlative studies&#xD;
western blotting: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Frequency of Adverse Events, Graded According to NCI CTCAE v3.0. Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE</description>
          <population>All treated and eligible patients</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Grade 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </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 Complete Response: During observation, no disease is apparent, including measurable and non-measurable disease, and no evidence of disease is observed for at least 28 days, as confirmed by a second assessment following the original observation of no disease; and Partial Response: A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the 50% or greater decrease, and no appearance of new lesions is noted.</description>
        <time_frame>Up to 43 weeks</time_frame>
        <population>All treated and eligible patients</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Colony-stimulating Factor and Monoclonal Antibody)</title>
            <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
pegfilgrastim: Given SC&#xD;
rituximab: Given IV&#xD;
flow cytometry: Correlative studies&#xD;
biopsy: Correlative studies&#xD;
immunohistochemistry staining method: Correlative studies&#xD;
western blotting: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate</title>
          <description>Overall Response is defined as Complete Response: During observation, no disease is apparent, including measurable and non-measurable disease, and no evidence of disease is observed for at least 28 days, as confirmed by a second assessment following the original observation of no disease; and Partial Response: A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the 50% or greater decrease, and no appearance of new lesions is noted.</description>
          <population>All treated and eligible patients</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60" lower_limit="38.7" upper_limit="78.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline</title>
        <description>Mean percent change in CD11b level from baseline at each visit</description>
        <time_frame>Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39</time_frame>
        <population>All treated and eligible patients</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Colony-stimulating Factor and Monoclonal Antibody)</title>
            <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
pegfilgrastim: Given SC&#xD;
rituximab: Given IV&#xD;
flow cytometry: Correlative studies&#xD;
biopsy: Correlative studies&#xD;
immunohistochemistry staining method: Correlative studies&#xD;
western blotting: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline</title>
          <description>Mean percent change in CD11b level from baseline at each visit</description>
          <population>All treated and eligible patients</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.2" spread="34.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-35.5" spread="28.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-24.7" spread="117.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-56.8" spread="27.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.8" spread="40.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 23</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.7" spread="35.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 31</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-18.7" spread="47.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 39</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.1" spread="42.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in CD20 Antigen Expression and Density of Expression</title>
        <description>Percent change in CD20 antigen expression and density of expression</description>
        <time_frame>At 4 years</time_frame>
        <population>Samples tissues were not large enough to perform analysis. No participants were analyze.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Colony-stimulating Factor and Monoclonal Antibody)</title>
            <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
pegfilgrastim: Given SC&#xD;
rituximab: Given IV&#xD;
flow cytometry: Correlative studies&#xD;
biopsy: Correlative studies&#xD;
immunohistochemistry staining method: Correlative studies&#xD;
western blotting: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in CD20 Antigen Expression and Density of Expression</title>
          <description>Percent change in CD20 antigen expression and density of expression</description>
          <population>Samples tissues were not large enough to perform analysis. No participants were analyze.</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>Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline</title>
        <description>Mean percent change in TNF level from baseline at each visit.</description>
        <time_frame>Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39</time_frame>
        <population>All treated and eligible patients</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Colony-stimulating Factor and Monoclonal Antibody)</title>
            <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
pegfilgrastim: Given SC&#xD;
rituximab: Given IV&#xD;
flow cytometry: Correlative studies&#xD;
biopsy: Correlative studies&#xD;
immunohistochemistry staining method: Correlative studies&#xD;
western blotting: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline</title>
          <description>Mean percent change in TNF level from baseline at each visit.</description>
          <population>All treated and eligible patients</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.5" spread="65.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.5" spread="47.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.2" spread="50.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3" spread="34.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.7" spread="76.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 23</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.2" spread="80.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 31</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.6" spread="100.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 39</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.2" spread="110.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline</title>
        <description>Mean percent change in INF level from baseline.</description>
        <time_frame>Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39</time_frame>
        <population>All treated and eligible patients</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Colony-stimulating Factor and Monoclonal Antibody)</title>
            <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
pegfilgrastim: Given SC&#xD;
rituximab: Given IV&#xD;
flow cytometry: Correlative studies&#xD;
biopsy: Correlative studies&#xD;
immunohistochemistry staining method: Correlative studies&#xD;
western blotting: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline</title>
          <description>Mean percent change in INF level from baseline.</description>
          <population>All treated and eligible patients</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-18.8" spread="33.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-27.8" spread="42.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.1" spread="124.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" spread="71.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="78.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 23</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.1" spread="43.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 31</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-33.0" spread="49.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 39</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.5" spread="45.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline</title>
        <description>Mean percent change in MFI level from baseline.</description>
        <time_frame>Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39</time_frame>
        <population>All treated and eligible patients</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Colony-stimulating Factor and Monoclonal Antibody)</title>
            <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
pegfilgrastim: Given SC&#xD;
rituximab: Given IV&#xD;
flow cytometry: Correlative studies&#xD;
biopsy: Correlative studies&#xD;
immunohistochemistry staining method: Correlative studies&#xD;
western blotting: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline</title>
          <description>Mean percent change in MFI level from baseline.</description>
          <population>All treated and eligible patients</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-32.0" spread="66.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22.4" spread="71.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-45.4" spread="66.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.4" spread="89.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.8" spread="137.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 23</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="219.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 31</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="295.8" spread="996.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 39</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0" spread="285.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Colony-stimulating Factor and Monoclonal Antibody)</title>
          <description>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.&#xD;
pegfilgrastim: Given SC&#xD;
rituximab: Given IV&#xD;
flow cytometry: Correlative studies&#xD;
biopsy: Correlative studies&#xD;
immunohistochemistry staining method: Correlative studies&#xD;
western blotting: Correlative studies</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Coronary artery occlusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Ventricular arrhythmia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="15" subjects_affected="11" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="11" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="25" subjects_affected="8" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="14" subjects_affected="7" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Supraventricular extrasystoles</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Vitreous floaters</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hiatus hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Intestinal mass</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="10" subjects_affected="7" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Infusion site pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Sensation of foreign body</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Cytokine release syndrome</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood albumin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase</sub_title>
                <counts group_id="E1" events="52" subjects_affected="15" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood creatine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood creatinine</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood glucose</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood glucose decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood potassium decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood sodium</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood sodium decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood sodium increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood uric acid increased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Body temperature increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Heart rate increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperalbuminaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyperphosphataemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" events="11" subjects_affected="6" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="17" subjects_affected="11" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Musculoskeletal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Burning sensation mucosal</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia nervosa</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nervousness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Bladder discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Cold sweat</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pallor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </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>Senior Administrator, Compliance - Clinical Research Services</name_or_title>
      <organization>Roswell Park Cancer Institute</organization>
      <phone>716-845-2300</phone>
    </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/NCT01682044
org study id: I 83106
secondary id: NCI-2011-00134
nct id: NCT01682044
nct alias: NCT00524628
lead sponsor: 
collaborator: 
has dmc: Yes
This phase II trial studies the side effects and how well giving pegfilgrastim together with
      rituximab works in treating patients with untreated, relapsed, or refractory follicular
      lymphoma, small lymphocytic lymphoma (SLL), or marginal zone lymphoma (MZL).
      Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells
      found in bone marrow or peripheral blood and may help the immune system recover from the side
      effects of therapy. Monoclonal antibodies, such as rituximab, can block cancer growth in
      different ways. Some block the ability of cancer to grow and spread. Others find cancer cells
      and help kill them or tumor cancer-killing substances to them. Giving pegfilgrastim together
      with rituximab may kill more cancer cells
PRIMARY OBJECTIVES:

      I. To evaluate the safety of Pegfilgrastim in combination with rituximab in patients with
      untreated or relapsed/refractory follicular, SLL or MZL.

      SECONDARY OBJECTIVES:

      I. To evaluate the efficacy (including overall response rate and durability of objective
      responses) of Pegfilgrastim in combination with rituximab in patients with untreated or
      relapsed/refractory follicular, SLL or MZL.

      II. To evaluate functional and phenotypic characteristics of host neutrophils undergoing
      treatment with Pegfilgrastim and rituximab.

      III. To evaluate changes in cluster of differentiation (CD)20 antigen expression and density
      of expression in patients receiving Pegfilgrastim and rituximab.

      IV. To evaluate changes in serum levels of tumor necrosis factor (TNF), interferon alpha
      (INFalpha) and free radical levels in patients undergoing treatment with Pegfilgrastim and
      rituximab.

      OUTLINE:

      Patients receive pegfilgrastim subcutaneously (SC) followed by rituximab intravenously (IV) 3
      days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 4 months for 1 year,
      every 6 months for 2 years, and then yearly for 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Adverse Events
time frame: Up to 90 days after the last dose of study drugs
description: Frequency of Adverse Events, Graded According to NCI CTCAE v3.0. Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE
measure: Overall Response Rate
time frame: Up to 43 weeks
description: Overall Response is defined as Complete Response: During observation, no disease is apparent, including measurable and non-measurable disease, and no evidence of disease is observed for at least 28 days, as confirmed by a second assessment following the original observation of no disease; and Partial Response: A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the 50% or greater decrease, and no appearance of new lesions is noted.
measure: Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline
time frame: Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39
description: Mean percent change in CD11b level from baseline at each visit
measure: Percent Change in CD20 Antigen Expression and Density of Expression
time frame: At 4 years
description: Percent change in CD20 antigen expression and density of expression
measure: Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline
time frame: Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39
description: Mean percent change in TNF level from baseline at each visit.
measure: Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline
time frame: Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39
description: Mean percent change in INF level from baseline.
measure: Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline
time frame: Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39
description: Mean percent change in MFI level from baseline.
arm group label: Treatment (colony-stimulating factor and monoclonal antibody)
arm group type: Experimental
description: Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: pegfilgrastim
description: Given SC
arm group label: Treatment (colony-stimulating factor and monoclonal antibody)
other name: Filgrastim SD-01
other name: GCSF-SD01
other name: Neulasta
other name: SD-01 sustained duration G-CSF
intervention type: Biological
intervention name: rituximab
description: Given IV
arm group label: Treatment (colony-stimulating factor and monoclonal antibody)
other name: IDEC-C2B8
other name: IDEC-C2B8 monoclonal antibody
other name: Mabthera
other name: MOAB IDEC-C2B8
other name: Rituxan
intervention type: Other
intervention name: flow cytometry
description: Correlative studies
arm group label: Treatment (colony-stimulating factor and monoclonal antibody)
intervention type: Procedure
intervention name: biopsy
description: Correlative studies
arm group label: Treatment (colony-stimulating factor and monoclonal antibody)
other name: biopsies
intervention type: Other
intervention name: immunohistochemistry staining method
description: Correlative studies
arm group label: Treatment (colony-stimulating factor and monoclonal antibody)
other name: immunohistochemistry
intervention type: Genetic
intervention name: western blotting
description: Correlative studies
arm group label: Treatment (colony-stimulating factor and monoclonal antibody)
other name: Blotting, Western
other name: Western Blot
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Francisco Hernandez-ILizaliturri
role: Principal Investigator
affiliation: Roswell Park Cancer Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Follicular
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, B-Cell, Marginal Zone
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Recurrence
mesh term: Rituximab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 