<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/NCT03269552</url>
  </required_header>
  <id_info>
    <org_study_id>9702</org_study_id>
    <secondary_id>NCI-2017-01548</secondary_id>
    <secondary_id>9702</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <secondary_id>RG1716046</secondary_id>
    <nct_id>NCT03269552</nct_id>
  </id_info>
  <brief_title>Carfilzomib With or Without Rituximab in the Treatment of Waldenstrom Macroglobulinemia or Marginal Zone Lymphoma</brief_title>
  <official_title>A Response-Adapted Clinical Trial of Weekly Carfilzomib With or Without Rituximab for Waldenström's Macroglobulinemia and Marginal Zone Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well carfilzomib with or without rituximab work in treating&#xD;
      patients with Waldenstrom macroglobulinemia or marginal zone lymphoma that is previously&#xD;
      untreated, has come back, or does not respond to treatment. Carfilzomib may stop the growth&#xD;
      of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with&#xD;
      monoclonal antibodies, such as rituximab, may induce changes in body's immune system and may&#xD;
      interfere with the ability of tumor cells to grow and spread. Giving carfilzomib alone when&#xD;
      disease is responding or with rituximab when disease is not responding may work better in&#xD;
      treating patients with Waldenstrom macroglobulinemia or marginal zone lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the overall response rate of single-agent weekly carfilzomib (CFZ), measured&#xD;
      after 2 cycles of therapy, in Waldenstrom's macroglobulinemia (WM) and marginal zone lymphoma&#xD;
      (MZL).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Assess safety and tolerability of single agent, weekly CFZ in patients with WM and MZL,&#xD;
      and determine the tolerability of weekly CFZ+rituximab for applicable patients.&#xD;
&#xD;
      II. Estimate the time to best response, response duration, and survival with weekly CFZ for&#xD;
      WM and MZL.&#xD;
&#xD;
      III. Evaluate the overall response rate associated with weekly CFZ in a subset of patients&#xD;
      with rituximab refractory WM or MZL.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 8, and 15.&#xD;
      Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or&#xD;
      unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for&#xD;
      Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2&#xD;
      courses of carfilzomib, receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and&#xD;
      then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for up to 1&#xD;
      year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated due to low accrual.&#xD;
  </why_stopped>
  <start_date type="Actual">December 18, 2017</start_date>
  <completion_date type="Actual">December 28, 2018</completion_date>
  <primary_completion_date type="Actual">December 28, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <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>Overall Response Rate</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Descriptive statistics will be used for baseline characteristics, and responses to treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Estimated using Kaplan-Meier analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Best Response</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Estimated using Kaplan-Meier analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Estimated using Kaplan-Meier analysis.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Marginal Zone Lymphoma</condition>
  <condition>Recurrent Marginal Zone Lymphoma</condition>
  <condition>Recurrent Waldenstrom Macroglobulinemia</condition>
  <condition>Refractory Marginal Zone Lymphoma</condition>
  <condition>Refractory Waldenstrom Macroglobulinemia</condition>
  <condition>Waldenstrom Macroglobulinemia</condition>
  <arm_group>
    <arm_group_label>Treatment (carfilzomib, rituximab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2 courses of carfilzomib, receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (carfilzomib, rituximab)</arm_group_label>
    <other_name>Kyprolis</other_name>
    <other_name>PR-171</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (carfilzomib, rituximab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (carfilzomib, rituximab)</arm_group_label>
    <other_name>ABP 798</other_name>
    <other_name>BI 695500</other_name>
    <other_name>C2B8 Monoclonal Antibody</other_name>
    <other_name>Chimeric Anti-CD20 Antibody</other_name>
    <other_name>CT-P10</other_name>
    <other_name>IDEC-102</other_name>
    <other_name>IDEC-C2B8</other_name>
    <other_name>IDEC-C2B8 Monoclonal Antibody</other_name>
    <other_name>MabThera</other_name>
    <other_name>Monoclonal Antibody IDEC-C2B8</other_name>
    <other_name>PF-05280586</other_name>
    <other_name>Rituxan</other_name>
    <other_name>Rituximab Biosimilar ABP 798</other_name>
    <other_name>Rituximab Biosimilar BI 695500</other_name>
    <other_name>Rituximab Biosimilar CT-P10</other_name>
    <other_name>Rituximab Biosimilar GB241</other_name>
    <other_name>Rituximab Biosimilar IBI301</other_name>
    <other_name>Rituximab Biosimilar PF-05280586</other_name>
    <other_name>Rituximab Biosimilar RTXM83</other_name>
    <other_name>Rituximab Biosimilar SAIT101</other_name>
    <other_name>RTXM83</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Waldenstrom's macroglobulinemia (WM) or marginal zone lymphoma (MZL) based on&#xD;
             institutional pathology review; patients may have either previously untreated or&#xD;
             relapsed/refractory disease&#xD;
&#xD;
          -  Measurable disease: for WM presence of monoclonal IgM immunoglobulin concentration on&#xD;
             serum electrophoresis, with lymphoplasmacytic marrow infiltrate; for MZL: measurable&#xD;
             nodal disease measuring at least 1.5 cm in longest dimension, or splenomegaly&#xD;
&#xD;
          -  Indication for initiation of therapy&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt; 1,000/uL unless disease-related (due to marrow&#xD;
             infiltration or splenomegaly)&#xD;
&#xD;
          -  Platelet count &gt; 75,000/uL unless disease-related (due to marrow infiltration or&#xD;
             splenomegaly)&#xD;
&#xD;
          -  Serum creatinine &lt; 2.5 mg/dL or creatinine clearance &gt; 30 cc/min&#xD;
&#xD;
          -  Bilirubin &lt; 2 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) &lt; 3 x ULN&#xD;
&#xD;
          -  All patients must be informed of the investigational nature of this study and have&#xD;
             given written consent in accordance with institutional and federal guidelines&#xD;
&#xD;
          -  Expected survival of &gt; 90 days&#xD;
&#xD;
          -  Females of childbearing potential (FCBP) must agree to pregnancy testing and to&#xD;
             practice contraception&#xD;
&#xD;
          -  Male subjects must agree to practice contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV), hepatitis C, or hepatitis B positivity&#xD;
             (subjects with hepatitis B surface antigen [SAg] or core antibody positivity, who are&#xD;
             receiving and responding to antiviral therapy directed at hepatitis B or are negative&#xD;
             for hepatitis B virus [HBV] deoxyribonucleic acid [DNA], are allowed)&#xD;
&#xD;
          -  Candidate for potentially curative antibiotic therapy for gastric mucosa-associated&#xD;
             lymphoid tissue (MALT); (gastric MALT lymphoma patients with stage I/II helicobacter&#xD;
             [H.] pylori positive lymphoma must fail therapy with H.-pylori directed therapy before&#xD;
             being considered for this study)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher&#xD;
&#xD;
          -  Known active central nervous system (CNS) involvement&#xD;
&#xD;
          -  Pregnant or lactating females&#xD;
&#xD;
          -  Inadequate cardiac function, as measured by left ventricular ejection fraction (LVEF)&#xD;
             that is less than or equal to 40%, or the presence of New York Heart Association&#xD;
             (NYHA) classification of greater than stage II congestive heart failure&#xD;
&#xD;
          -  Significant neuropathy (grades 3-4, or grade 2 with pain) within 14 days prior to&#xD;
             screening&#xD;
&#xD;
          -  Uncontrolled inter-current illness including, but not limited to, unstable angina,&#xD;
             recent myocardial infarction within 6 months of screening and uncontrolled cardiac&#xD;
             arrhythmias, psychiatric illness, or psychosocial difficulty that would limit&#xD;
             compliance with study requirements&#xD;
&#xD;
          -  Non-hematologic malignancy within the past 3 years with the exception of a) adequately&#xD;
             treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)&#xD;
             carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason grade 6 or&#xD;
             less with stable prostate-specific antigen levels; or d) cancer considered cured by&#xD;
             surgical resection or unlikely to impact survival during the duration of the 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>Stephen Smith</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <results_first_submitted>December 2, 2019</results_first_submitted>
  <results_first_submitted_qc>January 8, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 18, 2020</results_first_posted>
  <last_update_submitted>January 8, 2020</last_update_submitted>
  <last_update_submitted_qc>January 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</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, B-Cell, Marginal Zone</mesh_term>
    <mesh_term>Waldenstrom Macroglobulinemia</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>
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</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 2, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03269552/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>4 participants signed informed consent, met eligibility and continued on to study treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Carfilzomib, Rituximab)</title>
          <description>Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2 courses of carfilzomib will continue to receive carfolzomib for 4 more courses. In addition, they will also receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable toxicity.&#xD;
Carfilzomib: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Rituximab: 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="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Carfilzomib, Rituximab)</title>
          <description>Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2 courses of carfilzomib, receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable toxicity.&#xD;
Carfilzomib: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Rituximab: Given IV</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
          </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="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.25" lower_limit="59" upper_limit="69"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </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="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate</title>
        <description>Descriptive statistics will be used for baseline characteristics, and responses to treatment.</description>
        <time_frame>Up to 1 year</time_frame>
        <population>Participants who were evaluated after cycle 2 day 15 and prior to cycle 3 day 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Carfilzomib, Rituximab)</title>
            <description>Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2 courses of carfilzomib will continue to receive carfolzomib for 4 more courses. In addition, they will also receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable toxicity.&#xD;
Carfilzomib: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Rituximab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate</title>
          <description>Descriptive statistics will be used for baseline characteristics, and responses to treatment.</description>
          <population>Participants who were evaluated after cycle 2 day 15 and prior to cycle 3 day 1.</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="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very good partial response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Minor response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Estimated using Kaplan-Meier analysis.</description>
        <time_frame>Up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Carfilzomib, Rituximab)</title>
            <description>Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2 courses of carfilzomib, receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable toxicity.&#xD;
Carfilzomib: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Rituximab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Estimated using Kaplan-Meier analysis.</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="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Best Response</title>
        <description>Estimated using Kaplan-Meier analysis.</description>
        <time_frame>Up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Carfilzomib, Rituximab)</title>
            <description>Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2 courses of carfilzomib will continue to receive carfolzomib for 4 more courses. In addition, they will also receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable toxicity.&#xD;
Carfilzomib: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Rituximab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Best Response</title>
          <description>Estimated using Kaplan-Meier 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="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="0.5" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Progression</title>
        <description>Estimated using Kaplan-Meier analysis.</description>
        <time_frame>Up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Carfilzomib, Rituximab)</title>
            <description>Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2 courses of carfilzomib will continue to receive carfolzomib for 4 more courses. In addition, they will also receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable toxicity.&#xD;
Carfilzomib: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Rituximab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Progression</title>
          <description>Estimated using Kaplan-Meier analysis.</description>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events are reported from the time the subject receives their first dose of study drug through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Carfilzomib, Rituximab)</title>
          <description>Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2 courses of carfilzomib will continue to receive carfolzomib for 4 more courses. In addition, they will also receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable toxicity.&#xD;
Carfilzomib: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Rituximab: Given IV</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Microangiopathic Hemolytic Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="4"/>
              </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="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Flatulance</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Flu Like Symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Fluid Retention</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Warm Sensation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>White Blood Cell Count Decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Increased Cold Sensitivity</sub_title>
                <description>In fingertips</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Urination</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Renal Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </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="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </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="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Early termination due to low accrual leading to small number of subjects analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Stephen Smith</name_or_title>
      <organization>University of Washington</organization>
      <phone>206-606-6546</phone>
      <email>ssmith50@seattlecca.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/NCT03269552
org study id: 9702
secondary id: NCI-2017-01548
secondary id: 9702
secondary id: P30CA015704
secondary id: RG1716046
nct id: NCT03269552
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well carfilzomib with or without rituximab work in treating
      patients with Waldenstrom macroglobulinemia or marginal zone lymphoma that is previously
      untreated, has come back, or does not respond to treatment. Carfilzomib may stop the growth
      of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with
      monoclonal antibodies, such as rituximab, may induce changes in body's immune system and may
      interfere with the ability of tumor cells to grow and spread. Giving carfilzomib alone when
      disease is responding or with rituximab when disease is not responding may work better in
      treating patients with Waldenstrom macroglobulinemia or marginal zone lymphoma.
PRIMARY OBJECTIVES:

      I. Determine the overall response rate of single-agent weekly carfilzomib (CFZ), measured
      after 2 cycles of therapy, in Waldenstrom's macroglobulinemia (WM) and marginal zone lymphoma
      (MZL).

      SECONDARY OBJECTIVES:

      I. Assess safety and tolerability of single agent, weekly CFZ in patients with WM and MZL,
      and determine the tolerability of weekly CFZ+rituximab for applicable patients.

      II. Estimate the time to best response, response duration, and survival with weekly CFZ for
      WM and MZL.

      III. Evaluate the overall response rate associated with weekly CFZ in a subset of patients
      with rituximab refractory WM or MZL.

      OUTLINE:

      Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 8, and 15.
      Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or
      unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for
      Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2
      courses of carfilzomib, receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and
      then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up every 3 months for up to 1
      year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate
time frame: Up to 1 year
description: Descriptive statistics will be used for baseline characteristics, and responses to treatment.
measure: Overall Survival
time frame: Up to 1 year
description: Estimated using Kaplan-Meier analysis.
measure: Time to Best Response
time frame: Up to 1 year
description: Estimated using Kaplan-Meier analysis.
measure: Time to Progression
time frame: Up to 1 year
description: Estimated using Kaplan-Meier analysis.
arm group label: Treatment (carfilzomib, rituximab)
arm group type: Experimental
description: Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve at least 25% M-protein reduction for Waldenstrom's macroglobulinemia or partial response for marginal zone lymphoma after 2 courses of carfilzomib, receive rituximab IV weekly on days 1, 8, 15, and 22 of course 3 and then monthly on day 1 of courses 4-6 in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Carfilzomib
description: Given IV
arm group label: Treatment (carfilzomib, rituximab)
other name: Kyprolis
other name: PR-171
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (carfilzomib, rituximab)
intervention type: Biological
intervention name: Rituximab
description: Given IV
arm group label: Treatment (carfilzomib, rituximab)
other name: ABP 798
other name: BI 695500
other name: C2B8 Monoclonal Antibody
other name: Chimeric Anti-CD20 Antibody
other name: CT-P10
other name: IDEC-102
other name: IDEC-C2B8
other name: IDEC-C2B8 Monoclonal Antibody
other name: MabThera
other name: Monoclonal Antibody IDEC-C2B8
other name: PF-05280586
other name: Rituxan
other name: Rituximab Biosimilar ABP 798
other name: Rituximab Biosimilar BI 695500
other name: Rituximab Biosimilar CT-P10
other name: Rituximab Biosimilar GB241
other name: Rituximab Biosimilar IBI301
other name: Rituximab Biosimilar PF-05280586
other name: Rituximab Biosimilar RTXM83
other name: Rituximab Biosimilar SAIT101
other name: RTXM83
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stephen Smith
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell, Marginal Zone
mesh term: Waldenstrom Macroglobulinemia
mesh term: Recurrence
mesh term: Rituximab
mesh term: Antineoplastic Agents, Immunological
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Early termination due to low accrual leading to small number of subjects analyzed.
point of contact: 