<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/NCT02217163</url>
  </required_header>
  <id_info>
    <org_study_id>SGHMM1</org_study_id>
    <nct_id>NCT02217163</nct_id>
  </id_info>
  <brief_title>Carfilzomib, Cyclophosphamide, Dexamethasone in Transplant Eligible Newly Diagnosed High-risk Multiple Myeloma</brief_title>
  <official_title>Study of Carfilzomib in Transplant Eligible Newly Diagnosed High-risk Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Singapore General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Singapore General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with high risk multiple myeloma have shorter remission periods and reduced overall&#xD;
      survival. Prognostic significance of minimal residual disease negative remission is being&#xD;
      highlighted in many of the newer studies.&#xD;
&#xD;
      The current phase 2 study investigates the combination of carfilzomib together with&#xD;
      cyclophosphamide and dexamethasone in patients with high risk multiple myeloma in younger&#xD;
      transplant-eligible patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Carfilzomib is administered over 30 minutes as an infusion. For cycle 1 only, Carfilzomib is&#xD;
      administered at 20mg/m2 IV on days 1 and 2, followed by escalation to 36 mg/m2 on days 8,9,15&#xD;
      and 16 on a 28 day cycle. Patients who tolerate 36 mg/m2 dose are kept at this dose for the&#xD;
      subsequent cycles on Days 1, 2, 8, 9, 15, 16 on a 28 day cycle. Dose and schedule&#xD;
      modifications for intolerable side effects are detailed in the protocol. Additionally&#xD;
      Cyclophosphamide is given a fixed dose of 500mg once per week orally, along with&#xD;
      dexamethasone, given on the days of Carfilzomib administration, 30 minutes to 4 hours prior&#xD;
      to Carfilzomib. Patients will undergo blood tests weekly and serum protein electrophoresis&#xD;
      every 4 weeks during treatment. Within completion of 5 cycles of treatment, patients would&#xD;
      undergo stem cell collection using chemotherapy and GCSF mobilization. After completion of 6&#xD;
      cycles of treatment, autologous bone marrow transplantation will be performed. Three months&#xD;
      following bone marrow transplantation, subjects will undergo further 2 consolidation cycles.&#xD;
      After consolidation, subjects will undergo disease assessment by blood and subjects who are&#xD;
      in CR will undergo bone marrow investigations and MRD analysis MPFC. Patients who achieve MRD&#xD;
      negativity by MPFC will be managed expectantly by watch and wait. Patients who are MRD&#xD;
      positive at this stage will receive maintenance for 2 years or till disease progression.&#xD;
      Follow up would extend till a minimum of 2 years from completion of the study. At the end of&#xD;
      2 years post maintenance or expectant monitoring, subjects who are in CR will undergo disease&#xD;
      assessment by blood and bone marrow investigations and MRD analysis MPFC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">October 2020</completion_date>
  <primary_completion_date type="Actual">October 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>2 years</time_frame>
    <description>To study the progression free survival (PFS) in patients with newly diagnosed high risk multiple myeloma treated with Carfilzomib, Cyclophosphamide and Dexamethasone, followed by autologous bone marrow transplantation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Minimal residual disease negativity</measure>
    <time_frame>2 years</time_frame>
    <description>Minimal residual disease burden at different time points, as assessed by multi parameter flow cytometry (MPFC).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>2 years</time_frame>
    <description>OS is defined as the time from entering study to death of any cause.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Single Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The combination therapy of Carfilzomib, cyclophosphamide and dexamethasone (KCyd) will be used to treat eligible patients for up to 6 cycles.This will be followed by an autologous bone marrow transplantation and 2 further consolidation cycles of KCyd. Depending on their disease response, patients will be managed expectantly or be started on maintenance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib, , Cyclophosphamide, Dexamethasone</intervention_name>
    <description>Carfilzomib is administered intraveneously over 30 minutes. For cycle 1 only, Carfilzomib is administered at 20mg/m2 on Day 1 and 2, dose will be escalated to 36mg/m2 on Day 8,9,15 and 16 of the 28-days cycle. Patients who tolerate the 36mg/m2 dose are kept at this dose for the subsequent cycles on Day 1,2,8,9,15,16 on a 28 days cycle. Cyclophosphamide is given at a fixed dose of 500mg once per week orally, along with dexamethasone which is given on the days of Carfilzomib administration, 30 minutes to 4 hours prior to Carfilzomib infusion.</description>
    <arm_group_label>Single Arm</arm_group_label>
    <other_name>Kyprolis</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Newly diagnosed Multiple Myeloma AND Transplant eligible AND&#xD;
&#xD;
          2. High Risk as defined by:&#xD;
&#xD;
               -  International Staging System 3 OR&#xD;
&#xD;
               -  FISH abnormality of t(4,14), t(14;16), 17p deletion or 1q amp&#xD;
&#xD;
          3. Patients must have evaluable myeloma, with at least one of the following (Assessed&#xD;
             within 28 days of commencing the study)&#xD;
&#xD;
               -  Serum M protein &gt;/= 0.5g/dL or&#xD;
&#xD;
               -  Urine M protein &gt;200mg/24hr&#xD;
&#xD;
               -  Serum free light chains &gt;100mg/mL (involved light chain) and abnormal k/l ratio&#xD;
&#xD;
               -  For IgA patients who have no other means of measurement of disease, sIgA level&#xD;
                  &gt;0.75g/dL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Relapsed Myeloma&#xD;
&#xD;
          2. Non transplant eligible patient.&#xD;
&#xD;
          3. IgM subtype Myeloma&#xD;
&#xD;
          4. POEMS syndrome&#xD;
&#xD;
          5. Amyloidosis&#xD;
&#xD;
          6. Waldenstroms Macroglobulinemia&#xD;
&#xD;
          7. Radiation therapy to an extended field involving a significant volume of bone marrow&#xD;
             within 21 days of randomization (Limited site radiation allowed).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chandramouli Nagarajan, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Singapore General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>119074</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Singapore General Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>169608</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>August 12, 2014</study_first_submitted>
  <study_first_submitted_qc>August 13, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <last_update_submitted>October 15, 2020</last_update_submitted>
  <last_update_submitted_qc>October 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 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>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02217163
org study id: SGHMM1
nct id: NCT02217163
lead sponsor: 
has dmc: No
Patients with high risk multiple myeloma have shorter remission periods and reduced overall
      survival. Prognostic significance of minimal residual disease negative remission is being
      highlighted in many of the newer studies.

      The current phase 2 study investigates the combination of carfilzomib together with
      cyclophosphamide and dexamethasone in patients with high risk multiple myeloma in younger
      transplant-eligible patients.
Carfilzomib is administered over 30 minutes as an infusion. For cycle 1 only, Carfilzomib is
      administered at 20mg/m2 IV on days 1 and 2, followed by escalation to 36 mg/m2 on days 8,9,15
      and 16 on a 28 day cycle. Patients who tolerate 36 mg/m2 dose are kept at this dose for the
      subsequent cycles on Days 1, 2, 8, 9, 15, 16 on a 28 day cycle. Dose and schedule
      modifications for intolerable side effects are detailed in the protocol. Additionally
      Cyclophosphamide is given a fixed dose of 500mg once per week orally, along with
      dexamethasone, given on the days of Carfilzomib administration, 30 minutes to 4 hours prior
      to Carfilzomib. Patients will undergo blood tests weekly and serum protein electrophoresis
      every 4 weeks during treatment. Within completion of 5 cycles of treatment, patients would
      undergo stem cell collection using chemotherapy and GCSF mobilization. After completion of 6
      cycles of treatment, autologous bone marrow transplantation will be performed. Three months
      following bone marrow transplantation, subjects will undergo further 2 consolidation cycles.
      After consolidation, subjects will undergo disease assessment by blood and subjects who are
      in CR will undergo bone marrow investigations and MRD analysis MPFC. Patients who achieve MRD
      negativity by MPFC will be managed expectantly by watch and wait. Patients who are MRD
      positive at this stage will receive maintenance for 2 years or till disease progression.
      Follow up would extend till a minimum of 2 years from completion of the study. At the end of
      2 years post maintenance or expectant monitoring, subjects who are in CR will undergo disease
      assessment by blood and bone marrow investigations and MRD analysis MPFC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival
time frame: 2 years
description: To study the progression free survival (PFS) in patients with newly diagnosed high risk multiple myeloma treated with Carfilzomib, Cyclophosphamide and Dexamethasone, followed by autologous bone marrow transplantation.
measure: Minimal residual disease negativity
time frame: 2 years
description: Minimal residual disease burden at different time points, as assessed by multi parameter flow cytometry (MPFC).
measure: Overall Survival (OS)
time frame: 2 years
description: OS is defined as the time from entering study to death of any cause.
arm group label: Single Arm
arm group type: Experimental
description: The combination therapy of Carfilzomib, cyclophosphamide and dexamethasone (KCyd) will be used to treat eligible patients for up to 6 cycles.This will be followed by an autologous bone marrow transplantation and 2 further consolidation cycles of KCyd. Depending on their disease response, patients will be managed expectantly or be started on maintenance.
intervention type: Drug
intervention name: Carfilzomib, , Cyclophosphamide, Dexamethasone
description: Carfilzomib is administered intraveneously over 30 minutes. For cycle 1 only, Carfilzomib is administered at 20mg/m2 on Day 1 and 2, dose will be escalated to 36mg/m2 on Day 8,9,15 and 16 of the 28-days cycle. Patients who tolerate the 36mg/m2 dose are kept at this dose for the subsequent cycles on Day 1,2,8,9,15,16 on a 28 days cycle. Cyclophosphamide is given at a fixed dose of 500mg once per week orally, along with dexamethasone which is given on the days of Carfilzomib administration, 30 minutes to 4 hours prior to Carfilzomib infusion.
arm group label: Single Arm
other name: Kyprolis
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: No
last name: Chandramouli Nagarajan, MBBS
role: Principal Investigator
affiliation: Singapore General Hospital
facility: 
facility: 
country: Singapore
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Cyclophosphamide