<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/NCT03043105</url>
  </required_header>
  <id_info>
    <org_study_id>ZS-1159</org_study_id>
    <nct_id>NCT03043105</nct_id>
  </id_info>
  <brief_title>TCP Regimen in Newly Diagnosed MCD:a Prospective, Single-center, Single-arm, Phase-II Pilot Trial</brief_title>
  <official_title>Thalidomide, Cyclophosphamide and Prednisone in Newly Diagnosed Multicentric Castleman's Disease: a Prospective, Single-center, Single-arm, Phase-II Pilot Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking Union Medical College Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To explore the effectiveness and safety of thalidomide, cyclophosphamide and prednisone (TCP&#xD;
      regimen) in newly diagnosed Multicentric Castleman's disease (MCD) patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center, open-labeled , single arm, phase-II pilot study which aims to&#xD;
      evaluate the efficacy and safety of thalidomide, cyclophosphamide and prednisone (TCP&#xD;
      regimen) in newly diagnosed Multicentric Castleman's disease (MCD) patients.There would be&#xD;
      two phases of the study. The treatment and the response evaluation phase will last from the&#xD;
      time of enrollment up to 24 months (evaluation will be carried out every 3 months). The&#xD;
      follow-up phase to assess for progression of disease will last from 24 months (2 years) to 4&#xD;
      years after enrollment (evaluation will be carried out every 12 months).The total study&#xD;
      duration will be 4 years after the last patient starts study medication.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Anticipated">January 1, 2021</completion_date>
  <primary_completion_date type="Actual">January 1, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This will be a single center, single arm, phase-II pilot study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>open-labeled</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients With Durable Tumor and Symptomatic Response</measure>
    <time_frame>From baseline to the time point when a patient achieves treatment response for 24 weeks.</time_frame>
    <description>Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: &gt;=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 6 months.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months</time_frame>
    <description>Progression-free survival (PFS) is defined as the time to death or treatment failure. Treatment failure is defined as: sustained increase in grade ≥2 disease-related symptoms persisting ≥12 weeks; new disease-related grade ≥3 symptoms; sustained &gt;1 point increase in ECOG-PS persisting for ≥12 weeks; radiological progression; or initiation of another treatment for MCD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From date of randomization until the date of death from any cause, assessed up to 36 months.</time_frame>
    <description>Overall survival, defined as the time to patients' death, is measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SF-36 Score</measure>
    <time_frame>From baseline to 24 weeks after treatment.</time_frame>
    <description>SF-36 score is a self-administered scoring system which reflects a patient's general health status. SF-36 contains 8 dimensions, including physical functioning, role physical, role emotional, vitality, mental health, social functioning, bodily pain, and general health. Each dimension ranges from 0 to 100. Higher scores mean better outcome. SF-36 score at baseline was compared with SF-36 score at 24 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade)</measure>
    <time_frame>From initiation of TCP regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy.</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (patients with grades ≥1 would be included)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-related Serious Adverse Events as Assessed by CTCAE v4.0 ( ≥3 Grade)</measure>
    <time_frame>From initiation of TCP regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy.</time_frame>
    <description>Number of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 (patients with grades ≥3 would be included)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Multicentric Castleman Disease</condition>
  <arm_group>
    <arm_group_label>TCP regimen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Thalidomide, cyclophosphamide and prednisone （TCP regimen）would be used for newly-diagnosed symptomatic MCD patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thalidomide, cyclophosphamide and prednisone</intervention_name>
    <description>Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;&#xD;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;&#xD;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.</description>
    <arm_group_label>TCP regimen</arm_group_label>
    <other_name>TCP regimen</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  Inclusion Criteria:&#xD;
&#xD;
               -  ≥18 years, all race/ethnic groups in China；&#xD;
&#xD;
               -  Newly diagnosed and previously untreated (patients are allowed to have received&#xD;
                  oral prednisone for up to 1 week before enrollment) symptomatic MCD patients&#xD;
                  (symptomatic disease is defined by the presence of clinical symptoms with the&#xD;
                  NCI-CTCAE grading ≥1 that are attributable to the disease, and for which&#xD;
                  treatment is indicated);&#xD;
&#xD;
               -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2;&#xD;
&#xD;
               -  Clinical laboratory values meeting these criteria at screening: absolute&#xD;
                  neutrophil count ≥ 1•0 x 109/L, Platelets ≥ 50 x 109/L, Alanine aminotransferase&#xD;
                  (ALT) within 2•5 x upper limit of normal (ULN); total bilirubin within 2•5 x ULN;&#xD;
                  estimated glomerular filtration rate (according to MDRD formula) &lt;15ml/min;&#xD;
&#xD;
               -  Women of childbearing potential must agree to use birth control measures during&#xD;
                  the study and for at least 3 months after receiving the last dose of study agent,&#xD;
                  and must have a negative pregnancy test at screening period. Men must agree to&#xD;
                  use birth control measures during the study and for at least 3 months after&#xD;
                  receiving the last dose of study agent;&#xD;
&#xD;
               -  Informed consent must be signed.&#xD;
&#xD;
          -  Exclusion Criteria:&#xD;
&#xD;
               -  age under 18 years;&#xD;
&#xD;
               -  ECOG (eastern cooperative oncology group) status above 2;&#xD;
&#xD;
               -  Immunosuppressive or anti-neoplastic drugs within the last 3 months;&#xD;
&#xD;
               -  serious diseases including malignancy;&#xD;
&#xD;
               -  Plan to have babies within 1 year after enrollment (for women and men), or&#xD;
                  pregnancy / breast-feeding (for women);&#xD;
&#xD;
               -  Known hypersensitivity to study agents;&#xD;
&#xD;
               -  Active infection requiring systemic treatment;&#xD;
&#xD;
               -  Other severe concurrent disease (eg. uncontrolled diabetes, symptomatic coronary&#xD;
                  heart disease) that is likely to interfere with study procedures or results, or&#xD;
                  that in the opinion of the investigator would constitute a hazard for&#xD;
                  participating in this study;&#xD;
&#xD;
               -  Unwilling or unable to provide informed consent;&#xD;
&#xD;
               -  Unwilling to return for follow-up at PUMCH.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100005</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <results_first_submitted>February 9, 2020</results_first_submitted>
  <results_first_submitted_qc>April 5, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 16, 2020</results_first_posted>
  <last_update_submitted>April 5, 2020</last_update_submitted>
  <last_update_submitted_qc>April 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
    <investigator_full_name>Jian Li</investigator_full_name>
    <investigator_title>Associated professor in hematology</investigator_title>
  </responsible_party>
  <keyword>Multicentric Castleman's Disease</keyword>
  <keyword>Thalidomide, cyclophosphamide and prednisone (TCP regimen)</keyword>
  <keyword>Efficacy</keyword>
  <keyword>Safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Castleman Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thalidomide</mesh_term>
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</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>February 1, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/05/NCT03043105/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TCP Treatment Group</title>
          <description>The newly-diagnosed symptomatic MCD patients received thalidomide, cyclophosphamide and prednisone (TCP ) treatment. The accurate dose of TCP regimen is listed as follows.&#xD;
Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;&#xD;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;&#xD;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>TCP Treatment Group</title>
          <description>The newly-diagnosed symptomatic MCD patients received thalidomide, cyclophosphamide and prednisone (TCP ) treatment. The accurate dose of TCP regimen is listed as follows.&#xD;
Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;&#xD;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;&#xD;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
          </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="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40" lower_limit="20" upper_limit="63"/>
                  </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="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>East Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </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>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Durable Tumor and Symptomatic Response</title>
        <description>Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: &gt;=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 6 months.</description>
        <time_frame>From baseline to the time point when a patient achieves treatment response for 24 weeks.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TCP Treatment Group</title>
            <description>The newly-diagnosed symptomatic MCD patients received thalidomide, cyclophosphamide and prednisone (TCP ) treatment. The accurate dose of TCP regimen is listed as follows.&#xD;
Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;&#xD;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;&#xD;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Durable Tumor and Symptomatic Response</title>
          <description>Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: &gt;=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 6 months.</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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival</title>
        <description>Progression-free survival (PFS) is defined as the time to death or treatment failure. Treatment failure is defined as: sustained increase in grade ≥2 disease-related symptoms persisting ≥12 weeks; new disease-related grade ≥3 symptoms; sustained &gt;1 point increase in ECOG-PS persisting for ≥12 weeks; radiological progression; or initiation of another treatment for MCD.</description>
        <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TCP Treatment Group</title>
            <description>The newly-diagnosed symptomatic MCD patients received thalidomide, cyclophosphamide and prednisone (TCP ) treatment. The accurate dose of TCP regimen is listed as follows.&#xD;
Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;&#xD;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;&#xD;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>Progression-free survival (PFS) is defined as the time to death or treatment failure. Treatment failure is defined as: sustained increase in grade ≥2 disease-related symptoms persisting ≥12 weeks; new disease-related grade ≥3 symptoms; sustained &gt;1 point increase in ECOG-PS persisting for ≥12 weeks; radiological progression; or initiation of another treatment for MCD.</description>
          <units>months</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.32" lower_limit="17.22" upper_limit="29.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall survival, defined as the time to patients' death, is measured.</description>
        <time_frame>From date of randomization until the date of death from any cause, assessed up to 36 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TCP Treatment Group</title>
            <description>The newly-diagnosed symptomatic MCD patients received thalidomide, cyclophosphamide and prednisone (TCP ) treatment. The accurate dose of TCP regimen is listed as follows.&#xD;
Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;&#xD;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;&#xD;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall survival, defined as the time to patients' death, is measured.</description>
          <units>months</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.16" lower_limit="28.08" upper_limit="36.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in SF-36 Score</title>
        <description>SF-36 score is a self-administered scoring system which reflects a patient's general health status. SF-36 contains 8 dimensions, including physical functioning, role physical, role emotional, vitality, mental health, social functioning, bodily pain, and general health. Each dimension ranges from 0 to 100. Higher scores mean better outcome. SF-36 score at baseline was compared with SF-36 score at 24 weeks.</description>
        <time_frame>From baseline to 24 weeks after treatment.</time_frame>
        <population>Each patient is assessed by SF-36 scoring system, which contains 8 dimensions, including physical functioning, role physical, role emotional, vitality, mental health, social functioning, bodily pain, and general health.</population>
        <group_list>
          <group group_id="O1">
            <title>TCP Treatment Group</title>
            <description>The newly-diagnosed symptomatic MCD patients received thalidomide, cyclophosphamide and prednisone (TCP ) treatment. The accurate dose of TCP regimen is listed as follows.&#xD;
Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;&#xD;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;&#xD;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in SF-36 Score</title>
          <description>SF-36 score is a self-administered scoring system which reflects a patient's general health status. SF-36 contains 8 dimensions, including physical functioning, role physical, role emotional, vitality, mental health, social functioning, bodily pain, and general health. Each dimension ranges from 0 to 100. Higher scores mean better outcome. SF-36 score at baseline was compared with SF-36 score at 24 weeks.</description>
          <population>Each patient is assessed by SF-36 scoring system, which contains 8 dimensions, including physical functioning, role physical, role emotional, vitality, mental health, social functioning, bodily pain, and general health.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>physical functioning</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.1" spread="6.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>role physical</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.7" spread="10.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>role emotional</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.6" spread="10.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>vitality</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.1" spread="5.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mental health</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5" spread="5.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>social functioning</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.6" spread="6.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>bodily pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.8" spread="6.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>general health</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.1" spread="4.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade)</title>
        <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (patients with grades ≥1 would be included)</description>
        <time_frame>From initiation of TCP regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TCP Treatment Group</title>
            <description>The newly-diagnosed symptomatic MCD patients received thalidomide, cyclophosphamide and prednisone (TCP ) treatment. The accurate dose of TCP regimen is listed as follows.&#xD;
Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;&#xD;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;&#xD;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade)</title>
          <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (patients with grades ≥1 would be included)</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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-related Serious Adverse Events as Assessed by CTCAE v4.0 ( ≥3 Grade)</title>
        <description>Number of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 (patients with grades ≥3 would be included)</description>
        <time_frame>From initiation of TCP regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TCP Treatment Group</title>
            <description>The newly-diagnosed symptomatic MCD patients received thalidomide, cyclophosphamide and prednisone (TCP ) treatment. The accurate dose of TCP regimen is listed as follows.&#xD;
Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;&#xD;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;&#xD;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-related Serious Adverse Events as Assessed by CTCAE v4.0 ( ≥3 Grade)</title>
          <description>Number of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 (patients with grades ≥3 would be included)</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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Safety data were collected until 30 days after the last dose of study drugs, except for secondary primary malignancies (which were assessed throughout the duration of follow-up, up to 4 years). Secondary primary malignancies were assessed throughout the duration of follow-up, up to 3 years.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>TCP Treatment Group</title>
          <description>The newly-diagnosed symptomatic MCD patients received thalidomide, cyclophosphamide and prednisone (TCP ) treatment. The accurate dose of TCP regimen is listed as follows.&#xD;
Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;&#xD;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;&#xD;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </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="10" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>constipation</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Jian Li</name_or_title>
      <organization>Peking Union Medical College Hospital</organization>
      <phone>86-010-69155027</phone>
      <email>lijian@pumch.cn</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/NCT03043105
org study id: ZS-1159
nct id: NCT03043105
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To explore the effectiveness and safety of thalidomide, cyclophosphamide and prednisone (TCP
      regimen) in newly diagnosed Multicentric Castleman's disease (MCD) patients.
This is a single center, open-labeled , single arm, phase-II pilot study which aims to
      evaluate the efficacy and safety of thalidomide, cyclophosphamide and prednisone (TCP
      regimen) in newly diagnosed Multicentric Castleman's disease (MCD) patients.There would be
      two phases of the study. The treatment and the response evaluation phase will last from the
      time of enrollment up to 24 months (evaluation will be carried out every 3 months). The
      follow-up phase to assess for progression of disease will last from 24 months (2 years) to 4
      years after enrollment (evaluation will be carried out every 12 months).The total study
      duration will be 4 years after the last patient starts study medication.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This will be a single center, single arm, phase-II pilot study.
primary purpose: Treatment
masking: None (Open Label)
masking description: open-labeled
measure: Number of Patients With Durable Tumor and Symptomatic Response
time frame: From baseline to the time point when a patient achieves treatment response for 24 weeks.
description: Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: >=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 6 months.
measure: Progression-free Survival
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
description: Progression-free survival (PFS) is defined as the time to death or treatment failure. Treatment failure is defined as: sustained increase in grade ≥2 disease-related symptoms persisting ≥12 weeks; new disease-related grade ≥3 symptoms; sustained >1 point increase in ECOG-PS persisting for ≥12 weeks; radiological progression; or initiation of another treatment for MCD.
measure: Overall Survival
time frame: From date of randomization until the date of death from any cause, assessed up to 36 months.
description: Overall survival, defined as the time to patients' death, is measured.
measure: Change in SF-36 Score
time frame: From baseline to 24 weeks after treatment.
description: SF-36 score is a self-administered scoring system which reflects a patient's general health status. SF-36 contains 8 dimensions, including physical functioning, role physical, role emotional, vitality, mental health, social functioning, bodily pain, and general health. Each dimension ranges from 0 to 100. Higher scores mean better outcome. SF-36 score at baseline was compared with SF-36 score at 24 weeks.
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade)
time frame: From initiation of TCP regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy.
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (patients with grades ≥1 would be included)
measure: Number of Participants With Treatment-related Serious Adverse Events as Assessed by CTCAE v4.0 ( ≥3 Grade)
time frame: From initiation of TCP regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy.
description: Number of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 (patients with grades ≥3 would be included)
arm group label: TCP regimen
arm group type: Experimental
description: Thalidomide, cyclophosphamide and prednisone （TCP regimen）would be used for newly-diagnosed symptomatic MCD patients
intervention type: Drug
intervention name: Thalidomide, cyclophosphamide and prednisone
description: Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;
Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;
Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.
arm group label: TCP regimen
other name: TCP regimen
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking Union Medical College Hospital
investigator full name: Jian Li
investigator title: Associated professor in hematology
mesh term: Castleman Disease
mesh term: Thalidomide
mesh term: Prednisone
mesh term: Cyclophosphamide
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 